On June 2, 2025 Eli Lilly and Company (NYSE: LLY) reported new Phase 1 data showing that its folate receptor alpha (FRα) antibody-drug conjugate (ADC) (LY4170156) demonstrated an encouraging safety profile and anti-tumor activity across dose and FRα expression levels in women with heavily pre-treated platinum-resistant ovarian cancer, including patients previously treated with mirvetuximab soravtansine (Press release, Eli Lilly, JUN 2, 2025, View Source [SID1234653643]). A preliminary overall objective response rate (ORR) of 55% was observed at the potential recommended Phase 2 dose of 4 mg/kg. Lilly’s FRα targeting ADC is composed of an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker. These data will be presented today in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"ADCs have begun to change the treatment paradigm for some women with ovarian cancer, but a large proportion of patients still have a significant need for new therapies that improve outcomes regardless of FRα expression level," said Isabelle Ray-Coquard, M.D., Ph.D., president of the ENGOT (European Network of Gynecological Oncology Trial) group, medical oncologist at the Centre Léon Bérard Lyon France and principal investigator for the trial. "These initial data show activity across all doses and levels of FRα expression, including in patients previously treated with a FRα targeting treatment. Taken together with the emerging safety and tolerability profile, these data demonstrate early potential to meaningfully improve outcomes for women living with advanced ovarian cancer."

As of the March 9, 2025 data cutoff, the study enrolled 95 participants with high-grade serous ovarian cancer across four dose levels (2 – 6 mg/kg). Patients received a median of five prior systemic regimens (range 1-10), and 15% were previously treated with mirvetuximab soravtansine. Among the 95 patients, 51% had tumors with FRα expression less than 75%, 34% had FRα expression of 75% or higher, and 16% had expression results pending. Key endpoints were safety, pharmacokinetics, and anti-tumor activity per RECIST v1.1.

Efficacy results demonstrate responses at all dose levels, across all FRα expression levels, including in patients who progressed on prior mirvetuximab soravtansine. In the 58 efficacy-evaluable patients (37 patients remain ongoing prior to first response assessment and were therefore not yet efficacy-evaluable at the time of the data cutoff), the ORR was 45% (26/58 patients), and the disease control rate was 74% (43/58). At the potential recommended Phase 2 dose of 4 mg/kg, the ORR was 55% (11/20 patients). The most common treatment-emergent adverse events across all dose levels included nausea (64%), anemia (40%), fatigue (32%), vomiting (32%), diarrhea (28%), and neutropenia (27%). Treatment-emergent neuropathy and ocular toxicity has not been observed to date. No maximum tolerated dose has been established.

"We are excited to share these first clinical data for our FRα targeting ADC, demonstrating a promising tolerability and efficacy profile across all FRα expression levels," said David Hyman, M.D., Chief Medical Officer, Lilly. "Based on these results, we believe there is the potential to significantly expand the number of ovarian cancer patients who could benefit from a FRα ADC. We are now focused on rapidly advancing this potential new medicine into registrational Phase 3 clinical trials."

For more information on Lilly’s oncology pipeline click here.

About LY4170156
LY4170156 is an investigational, next-generation antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα). FRα is a cell-surface glycoprotein encoded by the gene FOLR1 that binds to the essential nutrients folic acid and reduced folates, bringing them into cells to facilitate cell division and growth.1,2 FRα is overexpressed in many solid tumors such as ovarian, non-small cell lung, and colorectal cancers.1,3,4

LY4170156 was designed to target FRα across expression levels with an improved therapeutic index. LY4170156 is composed of an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker (PSARlink). PSARlink’s unique structure "masks" the cytotoxic molecules enabling them to stay in the body longer, providing the potential to broaden the therapeutic index of ADCs. LY4170156 is currently being studied in patients with ovarian cancer as well as other FRα-expressing solid tumors, NCT06400472.

On June 2, 2025 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that the results of the Phase III SERENA-6 trial – sponsored by AstraZeneca – demonstrate the clinical value of the Guardant360 CDx test in a circulating tumor DNA-guided approach to detect and treat emerging resistance in 1st-line therapy ahead of radiological disease progression in breast cancer (Press release, Guardant Health, JUN 2, 2025, View Source [SID1234653659]). Study results were presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago and were published in The New England Journal of Medicine.

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SERENA-6 is the first global, double-blind, registrational Phase III trial to use a ctDNA-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression is detected in imaging scans. The novel trial design used ctDNA monitoring with the Guardant360 liquid biopsy test at the time of routine tumor scans to identify patients for early signs of endocrine resistance and the emergence of ESR1 mutations.

"SERENA-6 is a landmark study that is creating a new paradigm using liquid biopsy to enable a switch to a new treatment as soon as you see the cancer showing signs of resistance," said Helmy Eltoukhy, Guardant Health chairman and co-CEO. "This use of the Guardant360 CDx test highlights how we are pushing the boundaries of what can be done with liquid biopsy in characterizing disease and potential drug efficacy, providing insights that could potentially change clinical practice and improve outcomes in patients with advanced breast cancer."

Following detection of an ESR1 mutation without radiological disease progression, the endocrine therapy of patients was switched to AstraZeneca’s camizestrant from ongoing treatment with an aromatase inhibitor (AI), while continuing combination with the same cyclin-dependent kinase (CDK) 4/6 inhibitor. The trial demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumors had an emergent ESR1 mutation as detected by Guardant360 CDx.

About Guardant360 CDx

The first FDA-approved blood test for complete genomic testing, Guardant360 CDx is approved as a companion diagnostic fur multiple therapies in non-small cell lung cancer. It is also the only FDA-approved companion diagnostic for targeted therapy in advanced breast cancer patients with ESR1 mutations. The test is broadly covered by Medicare and commercial insurers, representing over 300 million lives. For more information, visit the Guardant360 CDx website.

On June 1, 2025 Taiho Oncology, Inc., and Cullinan Therapeutics, Inc., reported the publication of positive results from the REZILIENT1 trial in the peer-reviewed Journal of Clinical Oncology (JCO). REZILIENT1 is a Phase 1/2, global, multicenter study of zipalertinib (development code: CLN-081/TAS6417) in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) who have received prior therapy (Press release, Taiho, JUN 1, 2025, View Source [SID1234653566]). Results from the REZILIENT1 trial will be presented in a simultaneous oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #8503).

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The full publication, titled Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab, can be found here.

Highlights of the REZILIENT1 Phase 1/2 trial in the authors’ conclusions include:

Zipalertinib demonstrated clinically meaningful efficacy in the primary efficacy population (n=176), including 51 patients who had received prior amivantamab.
The confirmed objective response rate (ORR) was 35.2% overall, and median duration of response (mDOR) and progression-free survival were 8.8 months and 9.4 months, respectively.
In patients treated after prior platinum-based chemotherapy only (n=125), ORR was 40% with mDOR of 8.8 months.
The safety profile of zipalertinib was manageable and consistent with previously reported data.¹
In exploratory subgroup analyses:
Patients who had received prior amivantamab without other ex20ins-targeted therapy showed a confirmed ORR of 30% and mDOR of 14.7 months.
Patients with brain metastases showed a confirmed ORR of 30.9% and a mDOR of 8.3 months.
"Despite recent treatment advances for patients with EGFR ex20ins-mutant NSCLC, there is a lack of oral targeted therapies for patients whose tumors harbor these mutations," said principal investigator Zofia Piotrowska, MD, Assistant Professor, Medicine, Harvard Medical School and a clinical researcher and lung cancer medical oncologist at the Massachusetts General Hospital Cancer Center. "Findings from the Phase 1/2 REZILIENT1 trial support our understanding of zipalertinib as a potential targeted therapy option for patients living with previously treated recurrent or metastatic NSCLC harboring EGFR ex20ins mutations."

Taiho Oncology is actively recruiting patients in the Phase 3 REZILIENT3 trial (NCT05973773).

About REZILIENT1
REZILIENT1 (Researching Zipalertinib In EGFR Non-Small Cell Lung Cancer Tumors) is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in adult patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who have received prior therapy. The primary endpoints were ORR and DOR as assessed by blinded independent central review (ICR) per RECIST v1.1. Adverse events were characterized and graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0).

About Zipalertinib
Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA. Zipalertinib is investigational and has not been approved by any health authority.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

About EGFR Exon 20 Insertion Mutations
NSCLC is a common form of lung cancer and up to 4% of all cases have EGFR exon 20 insertions, which makes them the third most common EGFR mutation subtype.2 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations,3 with insertions at exon 20 accounting for up to 12% of these mutations.

On June 1, 2025 Johnson & Johnson reported new data from a Phase 1 study evaluating pasritamig (JNJ-78278343), a first-in-class bispecific antibody that activates T-cells to harness the body’s immune system against prostate cancer cells, showing promise in patients with advanced disease who have progressed after multiple lines of therapy (Press release, Johnson & Johnson, JUN 1, 2025, View Source;johnson-unveils-first-in-human-results-for-pasritamig-showing-early-anti-tumor-activity-in-prostate-cancer-302470142.html [SID1234653567]). These first data on pasritamig, from the first-in-human study, demonstrate that pasritamig appears well-tolerated and exhibits a promising antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC), highlighting the potential of KLK2 as a novel target for T-cell engagement in advanced disease.1 These data were presented as an oral presentation (Abstract #5017) at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and published simultaneously in The Journal of Clinical Oncology.

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Pasritamig is a novel T-cell engager designed to bind both CD3 on T-cells and KLK2—a prostate-specific antigen with minimal expression outside of the prostate. Pasritamig activates T-cells by binding to CD3 and directing them to KLK2- expressing tumor cells, engaging the body’s immune system to specifically target these cancerous cells. This differentiated approach aims to deliver a targeted treatment for patients with advanced prostate cancer, while potentially reducing the high-grade toxicities historically associated with T-cell engagers.

"These first-in-human results for pasritamig are highly encouraging, demonstrating that KLK2 is a viable target for T-cell engagers in metastatic castration-resistant prostate cancer," said Capucine Baldini*, M.D., Ph.D., Drug Development Department (DITEP), Institut Gustave Roussy, and presenting author. "The data show a promising safety profile, with manageable adverse events and no AEs leading to treatment discontinuations or ICANS observed, with 40 percent of patients having no treatment-related AEs at all. Given the limited treatment options for mCRPC, these findings support further investigation of pasritamig and the role of KLK2-targeted T-cell therapies as a potential new approach for patients with aggressive disease."

"Metastatic castration-resistant prostate cancer remains one of the most difficult stages of prostate cancer to treat, particularly for patients who haven’t responded well to previous treatments," said Jeff Infante, M.D., Vice President of Early Clinical Development and Translational Research at Johnson & Johnson Innovative Medicine. "This investigational approach underscores our commitment to developing innovative and practice-changing medicines that are well-tolerated and can be easily administered in community practice settings."

The Phase 1 first-in-human study (NCT04898634) evaluated 174 patients with ages ranging from 36 to 89 years old and on average having received four prior therapies (range 1-13). The recommended phase 2 dose (RP2D) of pasritamig was 3.5mg on day 1, 18mg on day 8, 300mg intravenously on day 15 and then once every six weeks. The RP2D safety group also included patients treated once every three weeks as the toxicity profiles were very similar. The RP2D efficacy group only included patients treated at the RP2D once every six weeks.1

Within the RP2D safety group (n=45), treated once every three or six weeks, 100 percent had previously received androgen receptor pathway inhibitors, 75.6 percent had undergone taxane chemotherapy, and 37.8 percent had been treated with Lutetium 177 vipivotide tetraxetan prostate-specific membrane antigen radioligand therapy.1 The most common treatment- related adverse events (TRAEs) were Grade 1/2 infusion-related reactions (24.4 percent), Grade 1 cytokine release syndrome (CRS) presenting as fever only (8.9 percent, no steroid or tocilizumab was administered) and no reports of higher grade CRS. No TRAEs leading to treatment discontinuation or dose reduction were reported and no immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. Grade 3 TRAEs were infrequent with 4.4 percent of patients reporting transient AST/ALT increases and neutropenia. There were no dose-limiting toxicities reported. The favorable safety profile of the RP2D regimen enabled convenient outpatient administration on a patient-friendly, once-every-six-weeks schedule.1

Of the patients in the RP2D efficacy group (n=33), treated once every six weeks, 42.4 percent achieved a 50 percent or greater reduction in their prostate-specific antigen (PSA) levels with a median rPFS of 7.9 months (95 percent confidence interval [CI] 2.9, not estimable [NE]) and 21.2 percent of patients continuing therapy. Treatment with pasritamig showed durable disease control and rPFS that compares favorably to historical data in heavily pretreated patients with mCRPC.1

Metastatic castration-resistant prostate cancer occurs in a significant portion of prostate cancer patients, with many progressing despite initial therapies.2 Overall survival from diagnosis of mCRPC patients ranges from 13.5 to 31.6 months, and lower in patients who have progressed on therapy.3 Treatment options remain limited, underscoring the urgent need for safer and more effective therapies.4

About Pasritamig (JNJ-78278343)
Pasritamig (JNJ-78278343) is an investigational T-cell-engaging bispecific antibody (bsAb) targeting human kallikrein 2 (KLK2) on prostate cancer cells and CD3 on T-cells. This approach is being evaluated in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC), a patient population with limited treatment options.

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic castration-resistant prostate cancer (mCRPC) is a challenging and aggressive stage of prostate cancer where the disease progresses despite androgen deprivation therapy.2 Patients often experience metastasis to bones and lymph nodes, leading to poor outcomes and limited treatment options, including chemotherapy and second-line hormone therapies.5 The median overall survival ranges from 13.5 to 31.6 months depending on the site of metastasis, with a typical range of 15–36 months across the broader population.3,6 Survival rates can vary significantly depending on factors such as prior treatment history, disease burden, and response to therapy. The need for more effective treatments is critical, as the disease continues to impact a large number of men globally, with mCRPC being responsible for a substantial number of prostate cancer-related deaths.

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]).

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"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.