On June 1, 2025 AstraZeneca reported positive results from the MATTERHORN Phase III trial showed perioperative treatment with Imfinzi (durvalumab) in combination with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) versus chemotherapy alone (Press release, AstraZeneca, JUN 1, 2025, View Source [SID1234653555]). Patients were treated with neoadjuvant Imfinzi in combination with chemotherapy before surgery, followed by adjuvant Imfinzi in combination with chemotherapy, then Imfinzi monotherapy. The trial evaluated this regimen versus perioperative chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

These results will be presented today during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (abstract #LBA5) and simultaneously published in The New England Journal of Medicine.

In a planned interim analysis, patients treated with the Imfinzi-based perioperative regimen showed a 29% reduction in the risk of disease progression, recurrence or death versus chemotherapy alone (based on an EFS hazard ratio [HR] of 0.71; 95% confidence interval [CI] 0.58-0.86; p<0.001). Estimated median EFS was not yet reached for the Imfinzi arm versus 32.8 months for the comparator arm. An estimated 78.2% of patients treated with the Imfinzi-based perioperative regimen were event-free at one year compared to 74.0% in the comparator arm; the estimated 24-month EFS rate was 67.4% versus 58.5%, respectively, signaling a greater magnitude of benefit over time for the Imfinzi-based regimen.

For the secondary endpoint of overall survival (OS), a strong trend was observed in favour of the Imfinzi-based perioperative regimen (HR=0.78; 95% CI 0.62-0.97; p=0.025). The trial will continue to follow OS, which will be formally assessed at the final analysis.

Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, and principal investigator for the trial, said: "Despite receiving curative-intent surgery and chemotherapy, patients with gastric and gastroesophageal cancers frequently develop recurrent disease. Results from the MATTERHORN trial showed that more than two-thirds of patients treated with a durvalumab-based perioperative regimen had not experienced a recurrence or were progression-free after two years. This new treatment approach should become the new standard of care in this setting based on these results."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "This immunotherapy-based perioperative regimen has the potential to change the clinical paradigm in early gastric and gastroesophageal junction cancers based on the reduction in risk of progression, recurrence or death by nearly a third and the strong trend towards improved survival. As the third positive trial of perioperative treatment with Imfinzi across multiple tumour types, the MATTERHORN trial further validates this approach and highlights our commitment to bringing novel therapies to early stages of disease where there is the greatest chance for cure."

Summary of results: MATTERHORN

Imfinzi-based regimen

(n=474)

Chemotherapy regimen

(n=474)

EFSi

Median EFS (95% CI) (in months)

NR (40.7-NR)

32.8 (27.9-NR)

HR (95% CI)

0.71

(0.58-0.86)

p-valueii

p<0.001

EFS rate at 12 months (%)

78.2

74.0

EFS rate at 24 months (%)

67.4

58.5

OS

mOS (in months)

NR

47.2

HR (95% CI)

0.78

(0.62-0.97)

p-valueiii

p=0.025

i. EFS rates are based on Kaplan Meier estimates.

ii. Threshold to declare statistical significance p-value<0.0239.

iii. Threshold to declare statistical significance p-value<0.0001.

Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-highest leading cause of cancer mortality.1 Nearly one million new patients were diagnosed with gastric cancer in 2022, with approximately 660,000 deaths reported globally.1 In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies.2 In 2024, there were approximately 43,000 drug-treated patients in the US, European Union (EU) and Japan with early-stage and locally advanced gastric or GEJ cancer.3 Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030.4

GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach.5

Disease recurrence is common in patients with resectable gastric cancer despite undergoing surgery with curative intent and treatment with neoadjuvant/adjuvant chemotherapy. Approximately one in four patients with gastric cancer who undergo surgery develop recurrent disease within one year, and one in four patients do not survive beyond two years, reflecting high unmet medical need.6-7 Additionally, the five-year survival rate remains poor, with less than half of patients alive at five years.8

MATTERHORN
MATTERHORN is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 948 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery. This was followed by Imfinzi or placebo every four weeks for up to 12 cycles after surgery (including two cycles of Imfinzi or placebo plus FLOT chemotherapy and 10 additional cycles of Imfinzi or placebo monotherapy).

In the MATTERHORN trial, the primary endpoint is EFS, defined as time from randomization until the date of one of the following events (whichever occurred first): RECIST (version 1.1, per blinded independent central review assessment) progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period; RECIST progression/recurrence during the adjuvant period; non-RECIST progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period or discovered during surgery; progression/recurrence confirmed by biopsy post-surgery; or death due to any cause. Key secondary endpoints include pCR rate, defined as the proportion of patients who have no detectable cancer cells in resected tumour tissue following neoadjuvant therapy, and OS. The trial enrolled participants in 176 centres in 20 countries, including in the US, Canada, Europe, South America and Asia.

Imfinzi
Imfinzi is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

In addition to its indications in GI cancers, Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC.

Imfinzi is approved in the US and other countries as a perioperative treatment in combination with neoadjuvant chemotherapy for muscle-invasive bladder cancer based on the NIAGARA Phase III trial. Additionally, Imfinzi plus standard-of-care Bacillus Calmette-Guérin induction and maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with high-risk non-muscle-invasive bladder cancer in the POTOMAC Phase III trial.

Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan.

Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers.

On June 1, 2025 AstraZeneca reported positive results from the SERENA-6 Phase III trial showed that camizestrant in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) (Press release, AstraZeneca, JUN 1, 2025, View Source [SID1234653554]). The trial evaluated switching to the camizestrant combination versus continuing standard-of-care treatment with an aromatase inhibitor (AI) (anastrozole or letrozole) in combination with a CDK4/6 inhibitor in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumours have an emergent ESR1 mutation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

These results will be presented today during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (abstract #LBA4) and simultaneously published in The New England Journal of Medicine.

Results showed the camizestrant combination reduced the risk of disease progression or death by 56% compared to standard-of-care treatment (based on a hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.31–0.60; p<0.00001) as assessed by investigator. Median PFS was 16.0 months for patients who switched to the camizestrant combination versus 9.2 months for the comparator arm. Importantly, a consistent PFS benefit was observed across all CDK4/6 inhibitors and clinically relevant subgroups in the trial, including analysis by age, race, region, time of ESR1 mutation detection and type of ESR1 mutation.

The camizestrant combination was also associated with a meaningful delay in time to deterioration in quality of life, where in an exploratory endpoint, the camizestrant combination reduced the risk of deterioration in global health status and quality of life by 47% compared with the AI combination (HR 0.53; 95% CI, 0.33-0.82; nominal p<0.001). The median time to deterioration of global health status was 23.0 months in patients treated with the camizestrant combination, versus 6.4 months in patients that continued treatment with the AI combination (EORTC QLQ-C30). The camizestrant combination also delayed the time to deterioration of pain compared with the AI combination.

Data for the key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of this interim analysis. However, a trend toward extended treatment benefit was observed with the camizestrant combination based on PFS2 (HR 0.52; 95% CI 0.33–0.81; p=0.0038 [interim analysis threshold p=0.0001]). The trial will continue to assess OS, PFS2 and other key secondary endpoints.

Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, London, UK, and co-principal investigator for the trial, said: "Today’s news marks a pivotal moment in breast cancer care and redefines how we think about drug resistance in this type of breast cancer. The results of the innovative SERENA-6 trial show that switching from an aromatase inhibitor to camizestrant in combination with any of the three CDK4/6 inhibitors after emergence of an ESR1 mutation more than halved the risk of disease progression or death and delayed deterioration in quality of life by nearly 18 months. This proactive approach exemplifies a new treatment strategy in oncology; by treating developing resistance before it causes disease progression and deterioration in quality of life, we can extend the benefit of 1st-line treatment to optimise patient outcomes."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumour DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer. Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this 1st-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of HR-positive breast cancer."

Summary of results: SERENA-6

Camizestrant + CDK4/6 inhibitor (n=155)

AI + CDK4/6 inhibitor

(n=155)

PFSi

Median PFS (months)

16.0 (12.7-18.2)

9.2 (7.2-9.5)

Hazard ratio (95% CI)

0.44 (0.31-0.60)

p-value

p<0.00001

Time to deterioration in global health status/quality of lifeii

Mean TTD (months)

23.0 (13.8-NC)

6.4 (2.8, 14.0)

Hazard ratio (95% CI)

0.53 (0.33-0.82)

p-value (nominal)

p<0.001

PFS2iii

Events

38

47

Hazard ratio (95% CI)

0.52 (0.33-0.81)

p-value

[interim analysis threshold P=0.0001]

P=0.0038

CI, confidence interval; HR, hazard ratio; NC, not calculable; TTD, time-to-deterioration.

i PFS was defined per RECIST v1.1. HR was estimated using the Cox proportional hazard model adjusted for stratification factors.

ii Assessments were conducted at baseline, weeks 4, 8 and 12 and then every 8 weeks until PFS2. Analysis conducted in patients with a baseline score and at least one post-baseline assessment. TTD in global health status/quality of life, an exploratory endpoint, was defined as the time from randomisation to first deterioration that was confirmed at a subsequent timepoint measured using the European Organisation for Research and Treatment of Cancer 30-item quality-of-life questionnaire (EORTC QLQ-30). Deterioration was defined as a decrease from baseline ≥16.6. HR was estimated using the Cox proportional hazard model stratified by time of ESR1 mutation detection (one test vs more than one test), and time from initiation of AI + CDK4/6i to randomisation (<18 months vs. ≥18 months).

iii HR was estimated using the Cox proportional hazard model adjusted for stratification factors. Final PFS2 analysis will occur at 158 PFS2 events.

The safety profile of camizestrant in combination with palbociclib, ribociclib or abemaciclib in SERENA-6 was consistent with the known safety profile of each medicine. Consistent with the longer duration of exposure to the combination of camizestrant and CDK4/6 inhibitors in the trial, Grade 3 or higher adverse events from all causes occurred in 60% of patients in the camizestrant arm versus 46% in the AI arm; the majority of which were haematological events typically associated with CDK4/6 inhibitor treatment and included neutropenia (45% vs. 34%), anaemia (5% vs. 5%) and leukopenia (10% vs. 3%). If experienced, photopsia – reported as brief flashes of light in the peripheral vision – did not impact daily activities of patients in the trial and was reversible. There were no structural changes in the eye or changes in visual acuity. No new safety signals were identified and discontinuation rates were very low and similar in both arms, with 1% patients discontinuing camizestrant and 2% patients discontinuing an AI. Discontinuation of the CDK4/6 inhibitor occurred in 1% of patients in both arms of the trial.

SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumour DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The novel trial design used ctDNA monitoring at the time of routine tumour scans to identify patients for early signs of endocrine resistance and the emergence of ESR1 mutations. Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to camizestrant from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor.

Based on the results of the SERENA-6 Phase III trial, camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) has been granted Breakthrough Therapy Designation (BTD) in the US by the Food and Drug Administration for the treatment of adult patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer upon emergence of ESR1 mutation during first-line endocrine-based therapy.

Notes

HR-positive breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.1 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.2

HR-positive breast cancer, characterised by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumours considered HR-positive and HER2-negative.2 ERs often drive the growth of HR-positive breast cancer cells.3

Globally, approximately 200,000 patients with HR-positive breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies that target estrogen receptor (ER)-driven disease, which are often paired with CDK4/6 inhibitors.4-6 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.6 Once this occurs, treatment options are limited and survival rates are low with 35% of patients anticipated to live beyond five years after diagnosis.2,6,7

Mutations in the ESR1 gene are a key driver of endocrine resistance and are widely tested for in clinical practice at time of disease progression on 1st-line therapies.8,9 These mutations emerge during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes.8,9 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment without disease progression.4

The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research.

SERENA-6
SERENA-6 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) versus treatment with an AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) in patients with HR-positive, HER2-negative advanced breast cancer (patients with either locally advanced disease, or metastatic disease) whose tumours have an emergent ESR1 mutation.

The global trial enrolled 315 adult patients with histologically confirmed HR-positive, HER2-negative advanced breast cancer, undergoing treatment with an AI in combination with a CDK4/6 inhibitor as 1st-line treatment. The primary endpoint of the SERENA-6 trial is PFS as assessed by investigator, with secondary endpoints including OS, and PFS2 by investigator assessment.

Camizestrant
Camizestrant is an investigational, potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist that is currently in Phase III trials for the treatment of HR-positive breast cancer.

AstraZeneca’s broad, robust and innovative clinical development programme, including the SERENA-6, SERENA-4, CAMBRIA-1 and CAMBRIA-2 trials, is evaluating the safety and efficacy of camizestrant when used as a monotherapy or in combination with CDK4/6 inhibitors to address a number of areas of unmet need in HR-positive, HER2-negative breast cancer.

Camizestrant has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations. In the SERENA-2 Phase II trial, camizestrant demonstrated PFS benefit versus Faslodex (fulvestrant) irrespective of ESR1 mutation status or prior treatment with CDK4/6 inhibitors in patients with ER-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy. The SERENA-1 Phase I trial demonstrated that camizestrant is well tolerated and has a promising anti-tumour profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors.

On June 1, 2025 BeOne Medicines Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company, reported it will present new data from the Arm C and D cohorts of the pivotal, global Phase 3 SEQUOIA trial of BRUKINSA (zanubrutinib) (Press release, BeiGene, JUN 1, 2025, View Source [SID1234653553]). The findings underscore the strong and consistent efficacy of BRUKINSA across CLL patient types, including high-risk mutation status. These data will be presented in two rapid oral presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Data from the Arm D of SEQUOIA demonstrate that treatment with BRUKINSA plus venetoclax has the potential to drive progression-free survival and overall deep and durable responses across the frontline CLL patient spectrum, including patients with high-risk mutational status. The best undetectable minimal residual disease (uMRD) rate in peripheral blood at a sensitivity level 10-4 was 59%. These efficacy responses observed in Arm D, despite the high proportion of high-risk patients enrolled, are in line with recent fixed-duration studies in fitter, healthier patient populations. Additionally, 11 patients in Arm D were able to discontinue treatment early due to meeting uMRD-guided stopping criteria, and 9 patients remain in ongoing clinical remission with sustained uMRD (1 patient discontinued study while in clinical remission), allowing them to remain treatment-free. In patients without del(17p) and TP53 mutations, 43% achieved uMRD by cycle 16 and 60% by cycle 28. These data were published today in the Journal of Clinical Oncology.

"While many first-line CLL studies have excluded patient populations with high-risk disease features, BeOne included those patients in SEQUOIA," said Lai Wang, Ph.D., Global Head of R&D at BeOne. "Nearly 88% of patients with del(17p) and /or TP53 treated with BRUKINSA plus venetoclax remain progression-free at 36 months, which represents an unprecedented outcome for a doublet regimen in this difficult-to-treat patient population. These new SEQUOIA data reinforce BRUKINSA’s versatility across the spectrum of CLL patients and reflect BeOne’s commitment to progressing a pipeline built to meet unmet patient needs and elevate the standard of care."

Arm D Highlights (Abstract 7009)
SEQUOIA Arm D investigated BRUKINSA plus venetoclax in 114 patients with treatment-naïve (TN) CLL / small lymphocytic lymphoma (SLL) with or without del(17p) and/or TP53 high-risk mutations. At a median follow-up of 31.2 months, the combination induced a high 24-month progression-free survival (PFS) rate of 92% (95% CI, 85-96%) and an impressive overall response rate (ORR) of 97%. The 24-month overall survival (OS) rate was 96% (95% CI, 90%-98%). Of those patients with del(17p) and/or TP53 mutations, 94% were progression-free at 24 months and 87.6% were progression-free at 36 months.

The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.

"The zanubrutinib and venetoclax combination achieved deep, durable responses across risk groups, including patients with TP53 mutations, with a generally manageable safety profile. Notably, several patients were able to discontinue treatment and maintain remission, highlighting the potential for time-limited therapy with meaningful disease control," said Mazyar Shadman, M.D., M.P.H., Associate Professor and Innovators Network Endowed Chair, Medical Director, Cellular Immunotherapy and the Bezos Family Immunotherapy Clinic at Fred Hutch Cancer Center. "Generating data to inform future CLL treatment strategies that allow for both continuous therapy and planned time off treatment is essential, particularly for high-risk patients who are the most likely to succumb to this disease."

Arm C Highlights (Abstract 7011)
Arm C of the SEQUOIA study investigated BRUKINSA monotherapy in patients with TN CLL / SLL and del(17p) mutations and is the largest prospective cohort of CLL/SLL patients with del(17p). At a median follow-up of over 5.5 years (65.8 months), most patients remained progression-free. Notably, at 60 months, 72.2% of patients who received BRUKINSA remained progression-free (95% CI, 62.4, 79.8). When adjusted for the impact of the COVID-19 pandemic, 73.0% of patients in the cohort remained progression-free (95% CI, 63.3, 80.6) at 60 months. The 60-month OS rate was 85.1% (95% CI, 76.9, 90.6) and 87.0% (95% CI, 79.0, 92.1) when adjusted for COVID-19. At the time of data cut-off, the ORR was 97.3%, and 62.2% of patients were still receiving treatment with BRUKINSA.

The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.

For additional information about our presence at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting, please visit our meeting hub: congress.beonemedicines.com.

About Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.1,2 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.2,3 Approximately 20,700 new cases of CLL will be diagnosed in the U.S. in 2024.3

About 50% of CLL patients have high-risk genetic features – including del(17p), TP53 or unmutated IGHV – that may limit the effectiveness of some treatments (e.g. chemotherapy) and increase the likelihood of disease progression.4,5

About SEQUOIA
SEQUOIA (NCT03336333) is a randomized, multicenter, global Phase 3 trial designed to evaluate the efficacy and safety of BRUKINSA in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The trial consists of three cohorts:

Cohort 1 (n=479): randomized 1:1 to receive BRUKINSA (n=241) or bendamustine plus rituximab (n=238) until disease progression or unacceptable toxicity, in patients not harboring del(17p); data from this group comprise the primary endpoint;
Cohort 2/Arm C (n=110): patients with del(17p) receiving BRUKINSA as a monotherapy; and
Cohort 3/Arm D (n=114): 66 patients with del(17p) and/or pathogenic TP53 mutation and 47 patients without del(17p) or TP53 were enrolled, with 110 patients receiving BRUKINSA in combination with venetoclax.
The results of Cohort 1 of the SEQUOIA study led to the regulatory approval of BRUKINSA monotherapy in the treatment of TN CLL in many countries across the world, including approvals by the U.S. Food and Drug Administration and the European Medicines Agency. The primary endpoint of the trial is progression-free survival (PFS), as assessed by an independent review committee (IRC). Secondary endpoints include investigator-assessed PFS, IRC- and investigator-assessed overall response rate (ORR), overall survival (OS), and safety, as well as PFS and ORR in patients with del(17p).

About BRUKINSA (zanubrutinib)
BRUKINSA is an orally available, small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA has the broadest label globally of any BTK inhibitor and is the only BTK inhibitor to provide the flexibility of once or twice daily dosing. Additionally, BRUKINSA is also the only BTK inhibitor to demonstrate superiority to another BTK inhibitor in a Phase 3 study.

The global BRUKINSA clinical development program includes about 7,100 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 75 markets, and more than 200,000 patients have been treated globally.

U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib)

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Waldenström’s macroglobulinemia (WM).
Mantle cell lymphoma (MCL) who have received at least one prior therapy.
Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.
The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including BRUKINSA.

Evaluate bilirubin and transaminases at baseline and throughout treatment with BRUKINSA. For patients who develop abnormal liver tests after BRUKINSA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI, discontinue BRUKINSA.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information including U.S. Patient Information.

On June 1, 2025 Gilead Sciences, Inc. (Nasdaq: GILD) reported Trodelvy (sacituzumab govitecan-hziy) plus Keytruda (pembrolizumab) reduced the risk of disease progression or death by 35% (HR: 0.65) versus standard of care Keytruda plus chemotherapy in first-line treatment for patients with PD-L1+ (CPS ≥10) metastatic triple-negative breast cancer (TNBC) (Press release, Gilead Sciences, JUN 1, 2025, View Source [SID1234653552]). Trodelvy when given in combination with Keytruda resulted in a median progression-free survival (PFS) of 11.2 months vs 7.8 months when Keytruda was given in combination with chemotherapy. These data from the pivotal Phase 3 ASCENT-04/KEYNOTE-D19 study will be presented today as a late-breaking oral presentation at the 2025 ASCO (Free ASCO Whitepaper) Annual Congress (Abstract #LBA109).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These results are an important advancement for patients with PD-L1–positive metastatic triple-negative breast cancer, a population for whom first-line options remain limited," said Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04 study. "By combining sacituzumab govitecan with pembrolizumab, we’re seeing meaningful gains in progression-free survival and a promising trend in overall survival—findings that could support a new frontline standard of care for this aggressive disease."

"The ASCENT-04 results build on Gilead’s aspiration of transforming the treatment of breast cancer with Trodelvy in earlier lines of therapy," said Dietmar Berger, MD, PhD. "Together with the recently reported clinically meaningful topline results from our first-line monotherapy study, these data reinforce our confidence in Trodelvy’s utility both as a single agent and in combination with immunotherapy in the frontline metastatic TNBC setting. We are actively engaging with the FDA to explore a potential regulatory path forward for this combination for the benefit of patients."

For the primary endpoint, the median PFS was 11.2 months (95% CI: 9.3-16.7) with Trodelvy plus Keytruda compared to 7.8 months (95% CI: 7.3-9.3) with Keytruda plus chemotherapy, with a median follow-up of 14 months. A highly statistically significant and clinically meaningful improvement was observed with Trodelvy plus Keytruda (n=221), showing a 35% reduction in the risk of disease progression or death (HR: 0.65; p<0.001) in the intent to treat population compared to standard of care Keytruda plus chemotherapy combination (n=222). The PFS benefit was generally consistent across key prespecified subgroups.

A numerically higher overall response rate was observed for the Trodelvy plus Keytruda combination [60% (95% CI: 52.9-66.3) versus 53% (95% CI: 46.4-59.9)], including 13% and 8% with a complete response, respectively, in the Trodelvy plus Keytruda and Keytruda plus chemotherapy arms. Notably, a substantially longer duration of response was observed with Trodelvy plus Keytruda [16.5 months (95% CI: 12.7-19.5) versus 9.2 months (95% CI: 7.6-11.3)]. Encouraging trends in overall survival (OS) were also observed, but data are immature at the time of PFS primary analysis. Overall survival follow-up remains ongoing and will continue to be monitored as a key secondary endpoint.

The safety profile of Trodelvy plus Keytruda in the ASCENT-04 study was consistent with the known safety profile of each agent. No new safety signals were identified with the combination and the combination did not exacerbate the safety profile of either therapy. The most frequent (≥10% of patients) grade ≥3 treatment-emergent adverse events with Trodelvy plus Keytruda were neutropenia (43%) and diarrhea (10%), and with Keytruda plus chemotherapy were neutropenia (45%), anemia (16%) and thrombocytopenia (14%). Fewer patients discontinued treatment due to adverse events on the Trodelvy plus Keytruda arm than with Keytruda plus chemotherapy (12% vs. 31%).

In addition to ASCENT-04, Gilead on May 23 announced topline results from ASCENT-03 demonstrating a highly statistically significant and clinically meaningful improvement in PFS compared to chemotherapy in patients with first-line metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitors. Detailed results from the ASCENT-03 study will be presented at a future medical meeting and discussed with regulatory authorities.

The use of Trodelvy plus Keytruda in patients with first-line PD-L1+ metastatic TNBC and Trodelvy as monotherapy in patients with first-line metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitors are investigational, and the safety and efficacy of these uses have not been established.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Triple-Negative Breast Cancer with PD-L1+ Tumors

TNBC is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC is diagnosed more frequently in younger and premenopausal women and is more prevalent in Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with mTNBC, the five-year survival rate is 12%, compared with 28% for those with other types of mBC.

Despite progress in treatment, first-line mTNBC has seen limited new approvals in recent years for tumors that express PD-L1+, and additional options are urgently needed. Despite recent advances, over 50% of patients do not receive treatment beyond first-line, reinforcing the urgent need for new options to help improve patient outcomes. Breast cancers expressing PD-L1 are overall more aggressive and associated with reduced survival time.

About the ASCENT-04/KEYNOTE-D19 Study

In 2021, Gilead entered a collaboration with Merck & Co. to investigate sacituzumab govitecan in combination with pembrolizumab in the Phase 3 trial, ASCENT-04/KEYNOTE-D19. The ASCENT-04/KEYNOTE-D19 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of sacituzumab govitecan in combination with pembrolizumab compared with treatment of chemotherapy plus pembrolizumab in patients with previously untreated, inoperable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1. The study enrolled 443 patients across multiple study sites.

Patients were randomized in a 1:1 ratio to receive either sacituzumab govitecan (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg intravenously on Day 1 of a 21-day cycle) or chemotherapy plus pembrolizumab. The chemotherapy regimen included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. Patients randomized to chemotherapy were allowed to crossover and receive sacituzumab govitecan upon disease progression.

The primary endpoint of the study is progression-free survival (PFS) as determined by BICR using RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs), and safety.

More information about ASCENT-04/KEYNOTE-D19 is available at ClinicalTrials.gov: NCT05382286.

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer.

Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer—including in curative settings—as well as in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.

INDICATIONS

TRODELVY (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
IMPORTANT SAFETY INFORMATION

BOXED WARNING: NEUTROPENIA AND DIARRHEA

TRODELVY can cause severe, life-threatening, or fatal neutropenia. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Primary prophylaxis with G-CSF is recommended for all patients at increased risk of febrile neutropenia. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
TRODELVY can cause severe diarrhea. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to TRODELVY.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur as early as the first cycle of treatment and may require dose modification. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm3 on Day 1 of any cycle or below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 of USPI.

Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤ Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions.

Nausea and Vomiting: TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

ADVERSE REACTIONS

In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY.

UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY.

Please see full Prescribing Information, including BOXED WARNING.

On June 1, 2025 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, reported two posters highlighting data updates for RP1 (vusolimogene oderparepvec) at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 30-June 3 in Chicago (Press release, Replimune, JUN 1, 2025, View Source [SID1234653551]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The new analyses we presented from the IGNYTE clinical trial of RP1 plus nivolumab in anti-PD-1 failed melanoma confirms our belief in the systemic activity of the combination, and also shows robust responses in injected liver and lung lesions with an acceptable safety profile," said Kostas Xynos, M.D., Chief Medical Officer of Replimune. "Additional data also presented at the meeting shows that RP1 can be handled safely with no additional biosafety protocols required confirming that standard disinfection procedures are sufficient for clean up."

Key findings are outlined below.

Poster Presentation: Response analysis for injected and non-injected lesions and the safety and efficacy of superficial and deep RP1 injection in the registrational cohort of anti-PD-1-failed melanoma patients of the IGNYTE trial (Track: Melanoma/Skin Cancers; June 1, 2025, 9:00 am – 12:00 pm CDT; Location: Hall A, Board 20; Abstract: 9537)

The poster included an analysis from the IGNYTE clinical trial of RP1 plus nivolumab in the cohort of anti-PD-1 failed melanoma patients (n=140). In the trial, the objective response rate (ORR) was 32.9% using RECIST 1.1. The complete response rate was 15.0% and landmark overall survival (OS) rates at 1, 2, and 3 years were 75.3%, 63.3%, and 54.8% respectively. Median OS has not been reached.
Patients experienced numerically higher objective response rates after receiving deep injections (± superficial) compared with superficial injections only. Deep responses were observed in injected and non-injected lesions.
The ORR by injection type using RECIST 1.1 was 29.8% when only superficial lesions were injected, 42.9% for deep/visceral plus superficial injections injected, and 40.9% when only deep/visceral lesions were injected.
There was a ≥30% reduction in 93.6% (73/78) of injected lesions and 79.0% (94/119) of non-injected lesions. The kinetics of response were similar in injected vs non-injected lesions.
Of the non-injected visceral organ lesions in responding patients, 96.2% (50/52) showed reduction from baseline, with 65.4% reduced by ≥30%.
RP1 injections directly into the lung and liver were generally well tolerated and resulted in few organ-specific adverse events that were easily managed.
Liver and lung injections had a tolerable safety profile.
No bleeding events were reported after liver injection.
Lung injections were associated with low rates of pneumothorax events, which were typically of low grade and manageable.
Overall, these data support the safety and efficacy of deep/visceral injections and demonstrate the development of a robust systemic anti-tumor response following treatment with RP1 plus nivolumab.
Poster Presentation: Biosafety analysis from the skin cancer cohorts in the IGNYTE clinical trial of RP1 (Track: Melanoma/Skin Cancers; June 1, 2025, 9:00 am – 12:00 pm CDT; Location: Hall A, Board 17; Abstract: 9534)

RP1 was assessed in various samples taken from patients.
This demonstrated that RP1 DNA is primarily detected at the injection site, consistent with RP1 replication in the tumor, and much more rarely on dressings, in blood, on mucous membranes or in urine.
In all cases, live RP1 was only rarely if ever detected, demonstrating that while residual RP1 DNA may be present, this does not indicate the presence of live RP1
There were no systemic herpetic infections in patients or reports of HSV-1 infections in contacts.
RP1 is completely neutralized using standard disinfectants within 30 seconds of contact, confirming that standard disinfection procedures are sufficient for RP1 clean-up.
Collectively these data demonstrate that the likelihood of transmission of RP1 to patients’ contacts or into the external environment is minimal, with no transmission having been reported to date.
Both posters will be available on the Company website under Events and Presentations.

About RP1
RP1 is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response.

About RP2
RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP-R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.