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New Data Show Genentech’s Itovebi Significantly Extended Survival in a Certain Type of HR-positive Advanced Breast Cancer

On May 31, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive final results from the overall survival (OS) analysis of the Phase III INAVO120 study. These data showed ItovebiTM (inavolisib), in combination with palbociclib (Ibrance) and fulvestrant, reduced the risk of death by more than 30% compared with palbociclib and fulvestrant alone (Press release, Genentech, MAY 31, 2025, View Source [SID1234653576]). This represents a statistically significant and clinically meaningful improvement in overall survival for people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The results are being presented in an oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published in the New England Journal of Medicine (NEJM).

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"For the first time, a PI3K pathway-targeted drug has shown it can help people with this breast cancer subtype live longer," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. "Itovebi exemplifies our continued commitment to improve survival rates for people with this common PIK3CA mutation, for whom more effective treatment options are needed."

"The landmark data for the inavolisib-based regimen showed not only a doubling in progression-free survival, but importantly that it extended lives and gave people more time without chemotherapy," said Professor Nicholas Turner, lead study author and professor of molecular oncology at The Institute of Cancer Research, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, London, United Kingdom. "These results give us confidence that this regimen could become the new standard of care in the first-line setting, having demonstrated a substantial benefit on patient outcomes and quality of life."

The Itovebi-based regimen demonstrated a meaningful OS benefit compared with palbociclib and fulvestrant alone. The median OS was 34.0 months (95% CI: 28.4–44.8) for people in the Itovebi arm, compared with 27.0 months (95% CI: 22.8–38.7) in the palbociclib and fulvestrant arm (stratified hazard ratio [HR]=0.67; 95% CI: 0.48–0.94, p-value=0.0190 [boundary=0.0469]). The benefit seen in delaying cancer progression was maintained in the updated analysis, with the Itovebi-based regimen showing a consistent improvement in median progression free survival of 17.2 months versus 7.3 months (stratified HR=0.42, 95% CI: 0.32-0.55) in the comparator arm.

The Itovebi-based regimen also led to a statistically significant improvement in objective response rate (the percentage of patients whose signs of cancer completely disappear or their tumors shrink significantly after treatment) and ad-hoc exploratory analyses showed it substantially delayed time to chemotherapy by approximately two years (stratified HR=0.43; 95% CI: 0.30-0.60). No new safety signals were observed at the time of the final OS analysis, with a low discontinuation due to adverse events supporting good tolerability.

Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored Phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations. We are exploring additional studies in breast cancer and other tumor types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations.

About the INAVO120 study

The INAVO120 study [NCT04191499] is a Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomization in the clinical trial to the time when the disease progresses, or a patient dies from any cause. Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.

Beyond INAVO120, Itovebi is currently being investigated in three additional company-sponsored Phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations:

in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine combination therapy (INAVO121; NCT05646862).
in combination with dual HER2 blockade versus dual HER2 blockade and optional physician’s choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239).
in combination with CDK4/6i and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in endocrine-sensitive, PIK3CA-mutated HR-positive/HER2-negative breast cancer (INAVO123; NCT06790693).
About hormone receptor (HR)-positive breast cancer

HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases. A defining feature of HR-positive breast cancer is that its tumor cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumor growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. The PI3K signaling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.

What is Itovebi?

Itovebi (inavolisib) is a prescription medicine used in combination with the medicines palbociclib and fulvestrant to treat adults who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has an abnormal phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) gene, and has spread to nearby tissue or lymph nodes (locally advanced), or to other parts of the body (metastatic), and has come back after hormone (endocrine) therapy.

Your healthcare provider will test your cancer for abnormal PIK3CA genes to make sure that Itovebi is right for you.

It is not known if Itovebi is safe and effective in children.

Important Safety Information

What are the possible side effects of Itovebi?

Itovebi may cause serious side effects, including:

High blood sugar levels (hyperglycemia). High blood sugar is common with Itovebi and may be severe. Your healthcare provider will monitor your blood sugar levels before you start and during treatment with Itovebi. Your blood sugar levels may be monitored more often if you have a history of Type 2 diabetes. Your healthcare provider may also ask you to self-monitor and report your blood sugar levels at home. This will be required more frequently in the first 4 weeks of treatment. If you are not sure how to test your blood sugar levels, talk to your healthcare provider. You should stay well-hydrated during treatment with Itovebi. Tell your healthcare provider right away if you develop symptoms of high blood sugar, including:
difficulty breathing
nausea and vomiting (lasting more than 2 hours)
stomach pain
excessive thirst
dry mouth
more frequent urination than usual or a higher amount of urine than normal
blurred vision
unusually increased appetite
weight loss
fruity-smelling breath
flushed face and dry skin
feeling unusually sleepy or tired
confusion
Mouth sores (stomatitis). Mouth sores are common with Itovebi and may be severe. Tell your healthcare provider if you develop any of the following in your mouth:
pain
swelling
redness
ulcers
Diarrhea is common with Itovebi and may be severe. Severe diarrhea can lead to the loss of too much body water (dehydration) and kidney injury. Tell your healthcare provider right away if you develop diarrhea, stomach-area (abdominal) pain, or see mucus or blood in your stool during treatment with Itovebi. Your healthcare provider may tell you to drink more fluids or take medicines to treat your diarrhea.
Your healthcare provider may tell you to decrease your dose, temporarily stop your treatment, or completely stop your treatment with Itovebi if you develop certain serious side effects.

The most common side effects and abnormal blood test results of Itovebi when used in combination with palbociclib and fulvestrant include:

decreased white blood cell counts, red blood cell counts, and platelet counts
decreased blood levels of calcium, potassium, sodium, and magnesium
increased creatinine blood levels
tiredness
increased blood levels of the liver enzyme alanine transaminase (ALT)
nausea
rash
loss of appetite
COVID-19 infection
headache
Itovebi may affect fertility in males and in females who are able to become pregnant. Talk to your healthcare provider if this is a concern for you.

These are not all the possible side effects of Itovebi. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or View Source You may also report side effects to Genentech at (877) 436-3683.

Before you take Itovebi, tell your healthcare provider about all of your medical conditions, including if you:

have a history of diabetes or high blood sugar
have kidney problems
are pregnant or plan to become pregnant. Itovebi can harm your unborn baby.
Females who are able to become pregnant:

Your healthcare provider will check to see if you are pregnant before you start treatment with Itovebi.
You should use effective non-hormonal birth control (contraception) during treatment with Itovebi and for 1 week after your last dose. Talk to your healthcare provider about what birth control method is right for you during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Itovebi.
Males with female partners who are able to become pregnant:

You should use effective birth control (contraception) during treatment with Itovebi and for 1 week after your last dose.
are breastfeeding or plan to breastfeed. It is not known if Itovebi passes into your breastmilk. Do not breastfeed during treatment with Itovebi and for 1 week after your last dose. Talk to your healthcare provider about the best way to feed your baby during treatment with Itovebi.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Please see additional Important Safety Information in the full Itovebi Prescribing Information or visit View Source

Avistone Announces Encouraging Results for Vebreltinib plus Andamertinib (PLB1004) in EGFR-mutated NSCLC with MET Amplification or Overexpression at ASCO Annual Meeting 2025

On May 31, 2025 Avistone Biotechnology Co., Ltd ("Avistone"), an innovative biotechnology company focused on precision oncology therapeutics, reported that the clinical data for Vebreltinib plus Andamertinib (PLB1004), its innovative combination of potent mesenchymal-epithelial transition factor (MET) inhibitor and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2025 (Press release, Avistone Pharmaceuticals, MAY 31, 2025, View Source [SID1234653575]).

The details of the poster presentation are provided below:

Poster title: Vebreltinib plus Andamertinib (PLB1004) in EGFR-mutated NSCLC with MET Amplification or Overexpression after failure on EGFR-TKIs treatment: phase Ib/II KYLIN-1 study
Abstract Number For Publication: 8632
Session: Poster Session-Lung Cancer- Non-Small Cell Metastatic
Location: Poster Board, 112
Session Date/Time: 5/31/2025 1:30pm-4:30pm CDT

MET amplification or overexpression is the most common "off-target" mechanism that drives resistance to EGFR-TKIs in NSCLC patients. The results from Phase Ib/II KYLIN-1 study (NCT06343064) showed that Vebreltinib plus Andamertinib demonstrated notable efficacy and manageable safety in EGFR-mutated NSCLC patients with MET amplification or overexpression after EGFR-TKIs failure.

Among the 56 patients enrolled at a dose of Vebreltinib 150mg BID plus Andamertinib 80mg QD (RP2D), the confirmed overall response rate (ORR) was 50.0%, and the median progression-free survival (mPFS) was 9.9 months. In 19 patients with brain metastases, ORR was 42.1% and mPFS was 9.5 months. Grade 3 or higher treatment related adverse events (TRAEs) occurred in 19.6% of the patients. None discontinued treatment or died due to TRAEs. No new safety signal was observed.

A multicenter Phase III study, KYLIN-3 study (NCT06970782), is currently ongoing to further evaluate Vebreltinib plus Andamertinib versus platinum-based doublet chemotherapy in patients with EGFR mutations, MET amplification and/or overexpression, locally advanced or metastatic NSCLC following EGFR-TKI failure.

To obtain a copy of the poster, please email Avistone.

About Vebreltinib

Vebreltinib is an orally, potent and selective c-Met inhibitor. Chinese National Medical Products Administration (NMPA) has formally approved the use of Vebreltinib in locally advanced or metastatic NSCLC patients with MET exon 14 skipping mutations, as well as adult patients with isocitrate dehydrogenase mutant astrocytoma with the PTPRZ1-MET fusion gene or glioblastoma with a history of low-grade disease who have the PTPRZ1-MET fusion gene and have failed previous treatments. Currently, Chinese Center for Drug Evaluation (CDE) has formally accepted its New Drug Application (NDA) and granted it priority review, intended for patients with locally advanced or metastatic NSCLC with MET amplification.

About Andamertinib (PLB1004)

Andamertinib (PLB1004) is an oral, potent, irreversible, and selective EGFR-TKI with potent blood-brain barrier penetration and broad tyrosine kinase activity. Preclinical studies have shown that it can effectively and irreversibly target exon 20 insertion. Additionally, it can also potently target classical EGFR mutations, such as Del19, L858R and T790M with a high degree of selectivity.

Libtayo® (cemiplimab) Phase 3 Data in the Adjuvant Treatment of Post-Surgical High-Risk Cutaneous Squamous Cell Carcinoma (CSCC) Have Potential to Be Practice-Changing

On May 31, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported detailed analyses from the Phase 3 C-POST trial, which evaluated PD-1 inhibitor Libtayo (cemiplimab) in patients with high-risk cutaneous squamous cell carcinoma (CSCC) after surgery (Press release, Regeneron, MAY 31, 2025, View Source [SID1234653550]). The results, shared during an oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published in the New England Journal of Medicine (NEJM), include additional data for the primary endpoint of disease-free survival (DFS) and the first presentation of key secondary endpoint outcomes.

"While surgery and radiotherapy remain the cornerstones of treatment for high-risk cutaneous squamous cell carcinoma, there is a critical unmet need for systemic therapies to help prevent relapse and metastasis to ultimately drive better outcomes for patients," said Danny Rischin, M.D., M.B.B.S., F.R.A.C.P., Research Lead, Head and Neck Cancer and Cutaneous SCC, Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, and lead investigator of the trial. "The Phase 3 C-POST trial demonstrates that cemiplimab is a highly active therapy in high-risk CSCC, with clinically meaningful outcomes across primary and secondary endpoints and exceptionally low rates of locoregional and distant recurrence."

Results from the C-POST trial shared earlier this year established Libtayo as the first immunotherapy to show a statistically significant and clinically meaningful benefit in high-risk CSCC in the adjuvant setting. In contrast, negative results with another PD-1 are presented at ASCO (Free ASCO Whitepaper). The data with Libtayo at this year’s ASCO (Free ASCO Whitepaper) provide additional insights for the primary endpoint of DFS – defined as time from randomization to the first documented disease recurrence or death – as well as first results for the secondary endpoints of freedom from locoregional recurrence, freedom from distant recurrence and overall survival (OS).

With a median duration of follow-up of 24 months (range: 2-64 months), efficacy results for Libtayo compared to placebo, were as follows:

68% reduction in the risk of disease recurrence or death (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.20-0.51; p<0.0001), with median DFS not reached for Libtayo-treated patients (versus 49 months for placebo)
At two years, DFS was 87% with Libtayo versus 64% with placebo
80% reduction in the risk of locoregional recurrence (HR: 0.20; 95% CI: 0.09-0.40)
65% reduction in the risk of distant recurrence (HR: 0.35; 95% CI: 0.17-0.72)
Updated OS data from a recent data cut, with approximately six months of additional follow up after the primary analysis for DFS, suggest an emerging OS benefit for Libtayo (HR: 0.78; 95% CI: 0.39-1.56) versus placebo.

"These results show the continued promise of Libtayo in non-melanoma skin cancers," said Israel Lowy, M.D., Ph.D., Clinical Development Unit Head, Oncology, at Regeneron. "Libtayo is the first medicine to demonstrate a statistically significant benefit in patients who have high-risk features for recurrence after resection of cutaneous squamous cell carcinoma and has the potential to become a new standard of care in the adjuvant setting. We are working with global regulatory authorities to bring this new option to patients as quickly as possible."

Additionally, an exploratory analysis of the C-POST results showed similar rates of DFS regardless of PD-L1 expression level. Specifically, Libtayo reduced the risk of disease recurrence or death by 72% in tumors with PD-L1 ≥1% (HR: 0.28; 95% CI: 0.15-0.52; n=309) and by 68% in tumors with PD-L1 <1% (HR: 0.32; 95% CI: 0.12-0.86; n=85), compared to placebo.

Safety was assessed in 205 patients in the Libtayo arm and 204 patients in the placebo arm. Adverse events (AEs) of any grade occurred in 91% and 89% of patients in the Libtayo arm and the placebo arm, respectively. Grade ≥3 AEs occurred in 24% and 14% of patients in the Libtayo arm and the placebo arm, respectively. The most common AEs occurring in at least 10% of patients in the Libtayo arm were fatigue, pruritus, rash, diarrhea, arthralgia, hypothyroidism and maculo-paplar rash. The only grade ≥3 AE that occurred in more than 2% of patients in the Libtayo arm was hypertension. Treatment discontinuations due to AEs, regardless of attribution, occurred in 10% and 2% of patients in the Libtayo arm and the placebo arm, respectively. Two patients experienced an AE leading to death in each arm.

The potential use of Libtayo described above is investigational, and its safety and efficacy has not been evaluated by any regulatory authority for this indication.

Regulatory applications have been submitted for Libtayo in the treatment of adjuvant CSCC in the United States and European Union.

About the Phase 3 Trial
C-POST is one of several trials from Regeneron’s oncology portfolio and pipeline being shared at ASCO (Free ASCO Whitepaper).

C-POST was a randomized, placebo-controlled, double-blind, multicenter, global Phase 3 trial investigating Libtayo versus placebo as adjuvant treatment for patients with features associated with a high-risk of CSCC recurrence and who had completed surgery and post-operative radiation therapy. Trial participants were at high risk of recurrence due to nodal features (extracapsular extension or ≥3 involved lymph nodes) and/or non-nodal features (in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with ≥1 additional poor prognostic features).

The trial enrolled 415 patients who were randomized to receive either Libtayo (n=209) or placebo (n=206) for up to 48 weeks. For the first 12 weeks, Libtayo 350 mg or placebo was administered intravenously every three weeks, followed by Libtayo 700 mg or placebo administered intravenously every six weeks for 36 weeks.

Mythic Therapeutics Presents Compelling Efficacy Data from its Phase 1 KisMET-01 Study Supporting Best-in-Class Potential of Novel cMET- ADC, MYTX-011, in Non-Small Cell Lung Cancer at the American Society of Clinical Oncology (ASCO) Annual Meeting

On May 31, 2025 Mythic Therapeutics, a clinical-stage biotechnology company developing next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported updated data from its Phase 1 KisMET-01 study evaluating its investigational cMET-targeting ADC candidate, MYTX-011, in patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC), in a poster at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Mythic Therapeutics, MAY 31, 2025, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-presents-compelling-efficacy-data-from-its-phase-1-kismet-01-study-supporting-best-in-class-potential-of-novel-cmet-adc-mytx-011-in-non-small-cell-lung-cancer-asco-2025 [SID1234653549]). MYTX-011 is a novel ADC engineered with pH-dependent binding to more precisely deliver anti-tumor payload across a range of cMET expression levels, with the goal of reducing toxicity and expanding the number of patients who can benefit from ADC therapy.

"We are highly encouraged by these early efficacy data demonstrating meaningful anti-tumor activity which underscore how our differentiated pH-dependent design may help unlock the full promise of ADCs to reshape cancer treatment and expand patient reach, regardless of histology and molecular subtype," said George Eliades, Ph.D., President and Chief Executive Officer at Mythic Therapeutics. "Together with a manageable tolerability profile, these findings support the potential of MYTX-011 to establish a new standard of care for pretreated NSCLC patients in second- and later-line settings, where effective treatment options remain extremely limited. We look forward to evaluating MYTX-011 in Part 2 of the study and plan to present updated expansion cohort data at an upcoming medical conference."

Data presented were from 66 patients treated at efficacious dose levels (≥4.0 mg/kg) administered once every three weeks (Q3W) in Part 1 of the dose escalation portion of the study. Patients had a median of three, and up to 10, prior lines of therapy with nearly half (45%) receiving prior taxane treatments. Preliminary results show:

Anti-tumor activity was consistent regardless of cMET expression levels, EGFR mutation status or prior taxane treatment.
In non-squamous, cMET+ tumors, the ORR was 39% in cMET high/intermediate (n=23) and 36% in cMET low tumors (n=11).
Responses were observed in patients with and without actionable genomic alterations, including a 50% ORR in patients with tumors containing both EGFR mutations and cMET high or intermediate expression.
Overall, responses were durable, with observed durations of up to 8.9 months and ongoing; the majority of patients with responses remain on treatment.
Disease control rate (DCR) was 80% at 12 weeks (n=24 of 30) and 52% at 24 weeks (n=14 of 27).
All four response-evaluable patients with squamous histology tumors and low cMET levels had clinical benefit; one partial response was observed and the three other patients had durable stable disease.
MTYX-011 demonstrated favorable pharmacokinetics (PK) and excellent stability. The overall safety profile of MYTX-011 was consistent with previously reported data, and no new safety signals were identified. The most common treatment-related adverse events (TRAEs) of any grade in 20% or more of patients included, blurred vision (47%), keratopathy (41%), keratitis (32%), nausea (29%), peripheral neuropathy (24%), fatigue (23%), and increased AST (21%). Grade 3 or higher TRAEs in 5% or more of patients included blurred vision (20%), keratopathy (18%), neutropenia (14%), and keratitis (11%). 11 of the 12 reports of neutropenia and 12 of the 16 cases of peripheral neuropathy occurred in patients treated at doses of 5.8 mg/kg or higher. Ocular AEs led to treatment discontinuation in four patients (6%), with three of the four patients receiving doses of 5.8 mg/kg or higher. Based on clinical data and favorable PK, a 5.0 mg/kg dose on a Q3W regimen with a 2-on, 1-off dose break schedule was selected as the recommended Phase 2 dose, which will be compared to a 4.0 mg/kg Q3W dose in Part 2 of the trial.

"The early data from the MYTX-011 study, showing compelling anti-tumor activity and durable responses in patients with lung cancer, together with a well-tolerated safety profile, are highly encouraging," said Rebecca Heist, M.D., MPH, Medical Oncologist, Massachusetts General Hospital, Cancer Center. "These findings suggest that MYTX-011 has the potential to become a promising new treatment option for a broad range of NSCLC patients, and we are eager to continue evaluating its efficacy and safety in the ongoing dose expansion phase of the study."

About KisMET-01

KisMET-01 (NCT05652868) is a multicenter, first-in-human Phase 1 study of MYTX-011 in patients with previously treated, locally advanced or metastatic NSCLC. The study is comprised of two parts: dose escalation (Part 1) in patients with NSCLC of any histology of cMET expression with cMET analyzed whenever tumor tissue is available, followed by dose expansion (Part 2) in cMET-positive (cMET+) patients selected by immunohistochemistry (Ventana SP44). cMET levels are defined as high (≥50% tumor cells with 3+ staining), intermediate (≥25% and <50% with 3+ staining), low (≥25% with 2+ staining, excluding high and intermediate), and ultra-low (≥75% excluding high, intermediate, and low).

About MYTX-011

MYTX-011 is an investigational cMET-targeting ADC, which leverages Mythic’s innovative FateControl technology. FateControl ADCs are pH engineered to unbind their target after internalization, intended to improve both tumor uptake and drug exposure for improved safety, tolerability and efficacy. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

KEYTRUDA® (pembrolizumab) Plus Trodelvy® (sacituzumab govitecan-hziy) Reduced Risk of Disease Progression or Death by 35% Versus KEYTRUDA Plus Chemotherapy in First-Line PD-L1+ Metastatic Triple-Negative Breast Cancer (TNBC)

On May 31, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that KEYTRUDA (pembrolizumab) plus Trodelvy (sacituzumab govitecan-hziy) reduced the risk of disease progression or death by 35% (HR=0.65, p<0.001) versus KEYTRUDA plus chemotherapy for the first-line treatment of patients with PD-L1+ (Combined Positive Score [CPS] ≥10) inoperable (unresectable) locally advanced or metastatic triple-negative breast cancer (TNBC), as determined by an FDA-approved test. KEYTRUDA, when given in combination with Gilead’s TROP2 antibody-drug conjugate (ADC) Trodelvy, resulted in a median progression-free survival (PFS) of 11.2 months versus 7.8 months when KEYTRUDA was given in combination with chemotherapy (Press release, Merck & Co, MAY 31, 2025, View Source [SID1234653548]). 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 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #LBA109) and were selected for the official ASCO (Free ASCO Whitepaper) Press Program.

"These results have the potential to be 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/KEYNOTE-D19 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 safety profile of KEYTRUDA plus Trodelvy in this study was consistent with the known safety profile of each agent. No new safety signals were identified with the combination. The two companies plan to share these results with regulatory authorities worldwide.

"We’re committed to building on the established role of KEYTRUDA as a foundational treatment for people with TNBC to provide new options in earlier lines of treatment, in the hope of improving outcomes for people living with this disease," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "These data support the addition of this TROP2-directed ADC to KEYTRUDA, demonstrating the potential to help people with TNBC and to give doctors another option to treat this disease."

A statistically significant and clinically meaningful improvement was observed with KEYTRUDA plus Trodelvy (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 KEYTRUDA plus chemotherapy (n=222). The PFS benefit was generally consistent across key prespecified subgroups including age, curative treatment-free interval and geographic region.

A higher objective response rate (ORR) was observed for the KEYTRUDA plus Trodelvy combination (59.7% [95% CI, 52.9-66.3] versus 53.2% [95% CI, 46.4-59.9]), including 13% and 8% with a complete response, respectively, in the KEYTRUDA plus Trodelvy and KEYTRUDA plus chemotherapy arms. Notably, a substantially longer duration of response (DOR) was observed with KEYTRUDA plus Trodelvy (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.

Merck has a comprehensive clinical development program in various subtypes of breast cancer including evaluating KEYTRUDA in combination with investigational TROP2 ADCs (trophoblast cell-surface antigen-directed antibody-drug conjugates) in metastatic and early-stage cancers. The company has four ongoing Phase 3 studies in breast cancer, with two being in metastatic disease.

In the U.S. and Europe, KEYTRUDA has two approved indications in TNBC: for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; and in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

As announced, data spanning more than 25 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting.

About the ASCENT-04/KEYNOTE-D19 Study

In 2021, Merck entered a collaboration with Gilead to investigate KEYTRUDA plus Trodelvy in the Phase 3 ASCENT-04/KEYNOTE-D19 open-label, global trial (ClinicalTrials.gov, NCT05382286). The primary endpoint is PFS as determined by BICR using RECIST v1.1. Secondary endpoints include OS, ORR, DOR, time to onset of response (TTR), patient-reported outcomes (PROs) and safety. The study enrolled 443 patients who were randomized in a 1:1 ratio to receive either sacituzumab govitecan (10 mg/kg intravenously [IV] on Days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg IV 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 and at this time patients randomized to chemotherapy were allowed to crossover and receive sacituzumab govitecan upon disease progression.

About triple-negative breast cancer (TNBC)

Triple-negative breast cancer is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a BRCA1 mutation.