On October 18, 2025 Genmab A/S (Nasdaq: GMAB) reported updated data from cohort B2 of the Phase 1/2 RAINFOL-01 trial evaluating rinatabart sesutecan (Rina-S), an investigational folate receptor alpha (FRα)-targeted, TOPO1-inhibitor antibody-drug conjugate (ADC). The study showed that at a median study follow-up of one year, treatment with Rina-S 100 mg/m² every 3 weeks (Q3W) resulted in a 50.0% confirmed objective response rate (ORR), including two complete responses (CR), in heavily pretreated patients with advanced endometrial cancer (EC) who had progressed following platinum-based chemotherapy and an immune checkpoint inhibitor. Additionally, at a median study follow-up of one year, 63.6% of responders (including CRs) in the 100 mg/m² cohort maintained their responses and remain on treatment. The responses were observed regardless of FRα expression levels. The updated results were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Berlin, Germany.

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Continued evaluation of single-agent Rina-S 100 mg/m2 in patients with advanced EC is ongoing in the Phase 2 RAINFOL-01 trial (NCT05579366) and the Phase 3 RAINFOL-03 trial (NCT07166094).

"Women with advanced endometrial cancer are often facing a difficult path, while doctors are confronted with not having enough treatment options," said Noelle Cloven, M.D., Texas Oncology Fort Worth, Sarah Cannon Research Institute, and study investigator. "That’s why these data signals with Rina-S in the updated Phase 1/2 RAINFOL-01 data are encouraging – they point to the possibility of providing more choices for patients in the future."

The B2 cohort of the Phase 1/2 RAINFOL-01 study (NCT05579366) is a dose expansion cohort evaluating the efficacy and safety of Rina-S in patients with advanced or recurrent endometrial cancer. In the study, 64 patients with heavily pretreated advanced or recurrent endometrial cancer whose disease had progressed on or after an anti-PD-(L)1 and platinum-based chemotherapy were enrolled and treated with Rina-S. Patients were administered either 100 mg/m2 (n=22) (selected dose for Phase 3 clinical trial) or 120 mg/m2 (n=42) of Rina-S. In the 100 mg/m2 cohort, the confirmed ORR was 50.0%, including two CRs. Anti-tumor activity was also observed in patients treated with Rina-S 120 mg/m2 Q3W, which resulted in 44.1% confirmed ORR and one CR. Study participants were previously treated with a median of three lines of therapy (range 1-8). Earlier results from this cohort were previously presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Common treatment emergent adverse events (TEAEs; all grades) consisted primarily of cytopenias and low-grade gastrointestinal (GI) events. To date, there have been no signals of ocular toxicities, neuropathy, or interstitial lung disease (ILD) observed in Rina-S clinical trials consistent with prior reports. Serious TEAEs (Grade 3 or higher), occurred in 36.4% and 52.4% of patients treated with Rina-S 100 mg/m2 and 120 mg/m2, respectively. Hematologic adverse events did not require significant dose reduction and were associated with low rates of treatment discontinuation.

"With this updated data, we are seeing additional momentum behind the possibilities of Rina-S," said Tahi Ahmadi, M.D., Executive Vice President and Chief Medical Officer, Head of Experimental Medicines at Genmab. "As a wholly owned, novel antibody-drug conjugate, Rina-S reflects Genmab’s vision to accelerate our innovative, late-stage pipeline that has the potential to redefine possibilities for patients with certain gynecologic cancers."

Rina-S is advancing through late-stage development supported by a growing portfolio of clinical trials, including the ongoing Phase 1/2 RAINFOL-01 trial (NCT05579366), the Phase 3 RAINFOL-03 trial (NCT07166094) in patients with endometrial cancer now underway and the Phase 3 RAINFOL-02 trial (NCT06619236) in patients with platinum resistant ovarian cancer (PROC). The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation (BTD) to Rina-S for the treatment of adult patients with recurrent or progressive EC who have disease progression on or following prior treatment with a platinum-containing regimen and a PD-(L)1 therapy.

About the RAINFOLTM -01 Trial
RAINFOL-01 (NCT05579366) is an open-label, multicenter Phase 1/2 study, designed to evaluate the safety and efficacy of rinatabart sesutecan (Rina-S) Q3W at various doses in solid tumors that are known to express FRα. The study consists of multiple parts including Part A dose escalation; Part B tumor-specific monotherapy dose-expansion cohorts; Part C platinum-resistant ovarian cancer (PROC) cohort; Part D combination therapy cohorts; Part F a monotherapy endometrial cancer (EC) cohort.

About Endometrial Cancer
Endometrial cancer (EC) starts in the lining of the uterus, known as the endometriumi and ranks as the second most prevalent gynecologic cancer globally, with increasing incidence and mortality ratesii,iii. Patients with advanced or recurrent EC have a relatively poor prognosis and treatment options are limited for those patients who have progressed following treatment with chemotherapy and immune checkpoint inhibitor. FRα is overexpressed on multiple tumors, including EC, making it a promising therapeutic target. Anti-tumor activity with Rina-S was observed across a broad range of FRα expression, and there are currently no approved FRα-directed therapies approved for the treatment of endometrial cancer.

About Rinatabart Sesutecan (Rina-S; GEN1184)
Rinatabart sesutecan (Rina-S; GEN1184) is an investigational ADC. It is composed of a novel human monoclonal antibody directed at folate receptor α (FRα), a novel hydrophilic protease-cleavable linker, and exatecan, a topoisomerase I inhibitor payload. The clinical trial program for Rina-S continues to expand including ovarian, endometrial and other cancers of unmet need.

(Press release, Genmab, OCT 18, 2025, View Source [SID1234656746])

On October 18, 2025 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported new preliminary data from its farnesyl transferase inhibitor (FTI) programs – darlifarnib (KO-2806) and tipifarnib – presented at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Berlin, Germany, from October 17 – 21, 2025.

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"Kura Oncology is pioneering the use of FTIs in combination with tyrosine kinase inhibitors (TKIs), PI3Kα inhibitors and KRAS inhibitors to address mechanisms of innate and adaptive resistance, thereby enhancing and extending the clinical benefit of these single-agent targeted therapies," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "The clinical data reported here at ESMO (Free ESMO Whitepaper) 2025 build on our preclinical presentation from last month and underscore darlifarnib’s transformative potential as a versatile combination partner to major classes of precision medicines."

Darlifarnib as Monotherapy in Advanced Solid Tumors – FIT-001 Phase 1 Trial

HRAS-mutant (HRAS-m) tumors are sensitive to FTIs
Manageable safety and tolerability profile at doses from 3 to 10 mg per day
Encouraging antitumor activity in advanced HRAS-m solid tumors across multiple dose levels, demonstrating on-target activity and a broad therapeutic window
Data support further evaluation of KO-2806 in combinations across tumor types

Darlifarnib + Cabozantinib in Renal Cell Carcinoma – FIT-001 Phase 1 Trial

FTI mechanism blocks hyperactivated mTORC1 signaling in tumor endothelial cells
Manageable safety profile in RCC patients across multiple doses, including at the full label dose of cabozantinib
Antitumor activity observed across all doses in RCC, including in prior cabozantinib-exposed patients
ORR: 33%–50% in ccRCC (17-50% in patients with prior cabozantinib exposure)
DCR: 80%–100% in ccRCC
Dose-escalation study ongoing and Phase 1b dose-expansion planned to assess optimal biologically active dose for combination

Tipifarnib + Alpelisib in PIK3CA-altered Head and Neck Squamous Cell Carcinoma – KURRENT-HN Phase 1 Trial

FTI mechanism blocks hyperactivated mTORC1 signaling in squamous tumor cells
Manageable safety profile in HNSCC patients across multiple doses
Robust antitumor activity was observed in heavily pretreated patients with relapsed or metastatic HNSCC with PIK3CA alterations
ORR: 47% was observed at a daily dose of tipifarnib 1200 mg + alpelisib 250 mg
Alpelisib monotherapy provides modest clinical benefit (ORR: 0%; BOR: SD)1 and tipifarnib monotherapy not expected to provide clinical benefit in this population
Data generation options for darlifarnib + PI3Kα inhibitor combinations in solid tumors are being assessed

"These results highlight the potential of FTIs to meaningfully enhance the clinical activity of PI3Kα inhibitors in molecularly selected patients," said Glenn Hanna, M.D., Director, Center for Cancer Therapeutic Innovation, Medical Oncologist, Center for Head & Neck Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School – an investigator on both the FIT-001 and KURRENT-HN trials. "Darlifarnib demonstrates robust activity in HRAS-mutant solid tumors, which are typically very challenging to treat using existing therapies. In addition, the combination of tipifarnib and alpelisib demonstrated robust antitumor activity in heavily pretreated patients with relapsed or metastatic HNSCC with PIK3CA alterations — a population where monotherapy alpelisib provides only modest clinical benefit. These combination data are very exciting and set the stage for combining darlifarnib with PI3Kα inhibitors."

Juric et al. J Clin Oncol 2018;36(13):1291-9.

Presentations
The presentations are available on Kura’s website at www.kuraoncology.com under the Posters and Presentations tab in the Farnesyl Transferase Inhibition section, and in the ESMO (Free ESMO Whitepaper) Congress 2025 online program.

Virtual Investor Event
Kura will host a webcast and conference call today, October 18, 2025, at 10:30 a.m. PT / 1:30 p.m. ET / 7:30 p.m. CEST featuring management and Glenn A. Hanna, M.D., Director, Center for Cancer Therapeutic Innovation Medical Oncologist, Center for Head & Neck Oncology, Dana-Farber Cancer Institute and Associate Professor of Medicine, Harvard Medical School.

The live webcast and replay will be available on the Company’s website at www.kuraoncology.com under the Investors tab in the Events and Presentations section.

(Press release, Kura Oncology, OCT 18, 2025, View Source [SID1234656745])

On October 18, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported results from a subgroup analysis of the CABINET phase 3 pivotal trial evaluating CABOMETYX (cabozantinib) versus placebo in patients with previously treated advanced neuroendocrine tumors (NET) originating in the lungs or thymus. These data will be presented at the 2025 European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) during the Monday Poster Session: Neuroendocrine Tumours on October 20, 2025, from 12:00 – 12:45 p.m. CEST.

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"The regulatory approvals of cabozantinib in the United States and European Union earlier this year provide a much-needed targeted treatment option for patients with previously treated advanced NET," said Jennifer Chan, M.D., M.P.H., study chair for the CABINET trial, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. "These subgroup results showing that cabozantinib achieved a meaningful progression-free survival benefit in patients with lung or thymic NET are encouraging, as these subtypes of the disease can be particularly challenging to treat."

In the phase 3 CABINET study, patients with locally advanced or metastatic pancreatic NET (pNET) or extra-pancreatic NET (epNET) were randomized 2:1 in separate cohorts to receive CABOMETYX 60 mg daily versus placebo. Patients with epNET had tumors arising in the gastrointestinal (GI) tract, lung, rare sites including the thymus and unknown primary sites. Of the 203 patients in the epNET cohort, 49 had lung or thymic NET. With a median follow-up for progression-free survival (PFS) of 5.5 months, CABOMETYX reduced the risk of disease progression or death by 81% versus placebo (stratified hazard ratio: 0.19; 95% confidence interval: 0.06-0.54; one-sided stratified log-rank P=0.0003). Median PFS was 8.2 months with CABOMETYX compared to 2.7 months with placebo. Confirmed objective response rates were 6% versus 0%, respectively.

"These subgroup data build upon the strong overall findings from the CABINET trial and reinforce the benefits of CABOMETYX for a heterogeneous NET patient population," said Dana T. Aftab, Ph.D., Executive Vice President, Research & Development, Exelixis. "Lung and thymic NET are forms of cancer with limited treatment options, and we are pleased CABOMETYX helps address an unmet need for these patients. We are committed to continuing to serve the NET patient community with our ongoing STELLAR-311 pivotal trial examining zanzalintinib as a potential first-line oral targeted therapy versus everolimus for patients with locally advanced or metastatic NET."

The safety profile of CABOMETYX observed in patients with lung or thymic NET was consistent with its known safety profile; no new safety signals were identified. The most frequent grade 3/4 adverse events attributed to CABOMETYX included fatigue (24%), hypertension (18%), diarrhea (9%) and palmar plantar erythrodysesthesia (9%).

In March 2025, the U.S. Food and Drug Administration approved CABOMETYX for the treatment of 1) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pNET; and 2) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated epNET, based on results from the CABINET study. In July 2025, the European Commission approved CABOMETYX for the treatment of adult patients with unresectable or metastatic, well-differentiated pNET and epNET who have progressed following at least one prior systemic therapy other than somatostatin analogues.

About CABINET (Alliance A021602)

CABINET (Randomized, Double-Blinded, Phase III Study of CABozantinib versus Placebo In Patients with Advanced NEuroendocrine Tumors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network, as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program.

CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase 3 pivotal trial that enrolled a total of 298 patients in two separate cohorts (pNET and epNET) in the U.S. at the time of the final analysis. Patients were randomized 2:1 to cabozantinib (60 mg) or placebo; each cohort was randomized separately and had its own statistical analysis plan. The trial was stopped early after an interim analysis showed superior efficacy associated with cabozantinib as compared to placebo in each of the two cohorts. Patients with epNET had primary tumors arising in the GI tract, lung, unknown primary sites and other organs. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior systemic therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by blinded independent central review. Secondary endpoints included overall survival, objective response rate and safety. More information about this trial is available at ClinicalTrials.gov.

About NET

NET are cancers that begin in the specialized cells of the body’s neuroendocrine system.2 These cells have traits of both hormone-producing endocrine cells and nerve cells.2 It is estimated that 161,000 to 192,000 people in the U.S. are living with unresectable, locally advanced or metastatic NET.3 The number of people diagnosed with NET has been increasing in recent decades.4 Functional NET release peptide hormones that can cause debilitating symptoms, like diarrhea, hypertension and flushing, while symptoms of non-functional NET are related primarily to tumor growth.5, 6, 7, 8, 9 Most NET take years to develop and grow slowly, but eventually all patients with advanced or metastatic NET will develop refractory and progressing disease.10, 11

NET can start in the pancreas (pNET), where they tend to be more aggressive, with a five-year survival rate of only 19% for advanced disease.2,12 NET can also develop in any part of the body, but most commonly start in the GI tract or in the lungs, where they have historically been referred to as carcinoid tumors and are more recently called epNET.2 The five-year survival rate for advanced GI NET is 68%.13 For advanced NET patients, treatment options include somatostatin analogs, chemotherapy, molecular targeted therapy and peptide-receptor radionuclide therapy.14

Approximately 2,000-4,500 people will be newly diagnosed with lung NET in the U.S. each year.15 The five-year survival rate for advanced lung NET is 49%.16 Thymic NET are rare, typically aggressive tumors with a worse prognosis compared to that of lung NET.17

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible; for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pNET; and adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated epNET. CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the EU. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: CABOMETYX can cause severe and fatal hemorrhages. The incidence of Grade 3-5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, each occurred in 1% of CABOMETYX patients. Monitor for signs and symptoms, and discontinue CABOMETYX in patients with Grade 4 fistulas or GI perforation.

Thrombotic Events: CABOMETYX can cause arterial or venous thromboembolic event. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events have occurred. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. In CABINET (n=195), hypertension occurred in 65% (26% Grade 3) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with antihypertensive therapy or for hypertensive crisis.

Diarrhea: CABOMETYX can cause diarrhea and it occurred in 62% (10% Grade 3) of treated patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1; resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): CABOMETYX can cause PPE and it occurred in 45% of treated patients (13% Grade 3). Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab in RCC can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. Monitor liver enzymes before initiation of treatment and periodically. Consider more frequent monitoring as compared to when the drugs are administered as single agents. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): CABOMETYX can cause ONJ and it occurred in <1% of treated patients. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution; resume at a reduced dose.

Impaired Wound Healing: CABOMETYX can cause impaired wound healing. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): CABOMETYX can cause RPLS. Perform evaluation for RPLS and diagnose by characteristic finding on MRI any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: CABOMETYX can cause thyroid dysfunction, primarily hypothyroidism, and it occurred in 19% of treated patients (0.4% Grade 3). Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment.

Hypocalcemia: CABOMETYX can cause hypocalcemia, with the highest incidence in DTC patients. Based on the safety population, hypocalcemia occurred in 13% of CABOMETYX patients (2% Grade 3 and 1% Grade 4).

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume CABOMETYX at a reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong or Moderate CYP3A4 Inducers: If coadministration with strong or moderate CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Pediatric Use: Physeal widening has been observed in children with open growth plates when treated with CABOMETYX. Physeal and longitudinal growth monitoring is recommended in children (12 years and older) with open growth plates. Consider interrupting or discontinuing CABOMETYX if abnormalities occur. The safety and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established.

Please see accompanying full Prescribing Information View Source

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

(Press release, Exelixis, OCT 18, 2025, View Source [SID1234656744])

On October 17, 2025 IDEAYA Biosciences, Inc. (the "Company") reported the first median overall survival ("OS") results from its Phase 1/2 clinical trial (OptimUM-01) evaluating darovasertib, the Company’s investigational oral protein kinase C ("PKC") inhibitor, in combination with Pfizer’s crizotinib, a c-MET inhibitor, as a first-line treatment for patients with metastatic uveal melanoma ("mUM"). The data will be presented on Sunday, October 26, 2025 by Dr. Justin Moser at the 2025 Society for Melanoma Research Congress ("SMR") taking place in Amsterdam, Netherlands.

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Data reported at SMR were from 44 first-line ("1L") mUM patients, including both HLA*A2:01-negative and HLA*A2:01-positive patients, in the single-arm Phase 1/2 OptimUM-01 trial with a median follow-up time of 25 months as of the cut-off date of May 28, 2025. Across all 44 patients treated with the darovasertib and crizotinib combination, a median OS of 21.1 months and a median progression free survival ("PFS") of 7.0 months was observed. In 41 efficacy-evaluable patients, the confirmed overall response rate by RECIST 1.1 was 34% (14/41) with a 9.0 month median duration of response. A disease control rate of 90% (37/41) was also observed, with 85% (35/41) of patients achieving ‘any reduction’ in target lesions. The combination continued to have manageable tolerability with the most common treatment-related adverse events ("TRAEs") (TRAEs >30%) of diarrhea, nausea, edema, vomiting, dermatitis, hypoalbuminemia, and fatigue. Grade ≥3 TRAEs were iron-deficiency anemia and pulmonary embolism (both 5%). The proportion of patients enrolled in the OptimUM-01 study that had baseline ECOG performance status scores ("PS") of 0 and 1 was 61% (27/44) and 39% (17/44), respectively. The proportion of patients with ECOG PS 1 in the OptimUM-01 study is approximately two times higher than an earlier published registrational study in mUM.

Metastatic uveal melanoma is a rare and aggressive form of ocular cancer with poor prognosis, where historical median OS reported in published meta-analysis from patients in the treatment naïve setting is approximately 12 months. The Company is conducting a registration-enabling Phase 2/3 trial (OptimUM-02) of the darovasertib and crizotinib combination in 1L HLA*A2:01-negative mUM and is targeting to report median PFS data from this trial by year-end 2025 to Q1 2026 to support a potential U.S. accelerated approval filing.

Pursuant to the Clinical Trial Collaboration and Supply Agreement with Pfizer to evaluate darovasertib and crizotinib as a combination therapy in mUM, Pfizer provided the Company with a defined quantity of crizotinib at no cost, as well as an additional defined quantity of crizotinib at a lump-sum cost.

A presentation summary of the SMR data will be available on the Investor Relations tab of the Company’s corporate website after the presentation.

Positive Phase 2 Data for Darovasertib in the Neoadjuvant Setting of Primary Uveal Melanoma

On October 20, 2025, the Company presented positive clinical data from its ongoing Phase 2 OptimUM-09 trial of neoadjuvant darovasertib in patients with primary uveal melanoma ("UM"). The data were presented in a Proffered Paper oral presentation by Dr. Marcus Butler, M.D., Associate Professor, Princess Margaret Cancer Center at the University of Toronto, at the 2025 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) ("ESMO") in Berlin, Germany.

Data presented at ESMO (Free ESMO Whitepaper) for neoadjuvant darovasertib were from a total of 95 patients with primary UM, including 56 patients recommended for enucleation ("EN") (surgical eye removal; Cohort 1) and 39 patients eligible for plaque brachytherapy ("PB") (Cohort 2) as of a data cut-off date of June 13, 2025. Patients were enrolled into Cohort 1 or Cohort 2 based on investigator recommended primary local therapy at baseline determined by tumor size and proximity to critical eye structures. All patients received neoadjuvant darovasertib for up to 12 cycles (or maximum benefit) prior to definitive primary local therapy. As of the cut-off date, only 94 patients were evaluable for efficacy, which reflects one patient in Cohort 2 that was excluded per protocol based on not yet receiving at least one dose of study drug and at least one post-baseline tumor assessment. Patients who derived benefit from darovasertib in the neoadjuvant setting were then eligible to receive darovasertib for up to six additional cycles as adjuvant therapy and monitored for disease recurrence and changes in visual acuity.

Key Findings from OptimUM-09

•
Tumor shrinkage and eye preservation

•
83% (78/94) of patients demonstrated ocular tumor shrinkage, with 54% (51/94) achieving ≥20% tumor shrinkage.

•
Patients recommended for EN (Cohort 1) demonstrated robust ocular tumor shrinkage following treatment with darovasertib, with approximately 84% (47/56) experiencing any reduction in tumor size by product of diameters, and 50% (28/56) and 37.5% (21/56) achieving a ≥20% and ≥30% reduction, respectively.

•
Similarly, among patients eligible for PB (Cohort 2), approximately 82% (31/38) achieved any reduction in ocular tumor size by product of diameters, with 60.5% (23/38) and 44.7% (17/38) demonstrating a ≥20% and ≥30% reduction, respectively.

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Among 42 patients in Cohort 1 who had completed primary local therapy at the time of the data cut, a 57.1% (24/42) eye preservation rate was observed. Of these patients, 75% (18/24) received PB and 25% (6/24) received external beam radiation instead of the EN procedure.

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Among patients in Cohort 1 with ≥20% tumor shrinkage prior to primary local therapy, the eye preservation rate jumped to 95% (19/20). Based in part on these data, and after discussions with the FDA, the Company has proposed ≥20% tumor shrinkage as the definition of response in primary UM for their ongoing Phase 3 trial (OptimUM-10) of darovasertib in the neoadjuvant setting.

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Predicted radiation reduction and visual preservation

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Among 37 evaluable patients with paired dosimetry in Cohort 2, approximately 70% (26/37) observed any reduction in the predicted dose of radiation to critical eye structures (fovea, disc, lens) compared to baseline following treatment with darovasertib in the neoadjuvant setting, with approximately 35-40% experiencing a ≥20% reduction. This magnitude of reduction is relevant since a similar decrease in radiation to the tumor apex is associated with improved visual outcomes.

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64.9% (24/37) of the evaluable patients in Cohort 2 had a reduced predicted risk of vision loss at 3-years post-PB based on a vision prognostic tool developed at the Cleveland Clinic that is used to predict the risk of developing 20/200 vision (legal blindness) or worse following radiation administered during PB.

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Improved visual acuity during neoadjuvant treatment

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54.7% (29/53) of patients in Cohort 1 and 60.5% (23/38) of patients in Cohort 2 demonstrated an improvement in visual acuity scores ("VAS") during neoadjuvant darovasertib therapy, compared to baseline.

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Patients in Cohort 1 with improved VAS scores from baseline had a mean gain of 17 letters on treatment, with ~72% (21/29) gaining ≥5 letters at 2 consecutive visits.

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Similarly, patients in Cohort 2 with improved VAS scores from baseline had a mean gain of 10 letters while on treatment, with ~52% (12/23) gaining ≥5 letters at 2 consecutive visits.

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Safety and Tolerability:

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Darovasertib was generally well tolerated with manageable adverse events, which included low-grade diarrhea, nausea, vomiting, and fatigue.

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Grade 3 or higher TRAEs occurred in 16.8% (16/95) of patients. Rates of treatment-related serious adverse events (5.3%) and treatment discontinuation due to adverse events (6.3%) were low.

Darovasertib has received U.S. Food and Drug Administration Breakthrough Therapy Designation in the neoadjuvant setting of primary uveal melanoma for EN eligible patients. The Company is currently conducting a Phase 3 trial (OptimUM-10) of darovasertib as a single-agent in the neoadjuvant setting of primary UM. The Company is also targeting to report topline median PFS data from its registration-enabling Phase 2/3 trial (OptimUM-02) evaluating darovasertib in combination with crizotinib in first-line, HLA*A2:01-negative metastatic UM by the end of 2025 to Q1’26 to enable a potential accelerated approval filing in the United States.

(Press release, Ideaya Biosciences, OCT 17, 2025, View Source [SID1234656820])

On October 17, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Libtayo (cemiplimab) as an adjuvant treatment for adult patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence after surgery and radiation. The European Commission is expected to make a final decision on the application in the coming months. Libtayo was approved by the U.S. Food and Drug Administration (FDA) for these patients in the U.S. earlier this month.

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The positive opinion is supported by results from the global Phase 3 C-POST trial investigating adjuvant Libtayo versus placebo in patients with CSCC at high risk of recurrence following surgery and radiation. In the trial, Libtayo reduced the risk of disease recurrence or death by 68% compared to placebo (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.20-0.51; p<0.0001). Fewer patients treated with Libtayo had locoregional or distant recurrence compared with those who received placebo (4% vs. 17% and 5% vs. 13%, respectively). Detailed data were published in the New England Journal of Medicine (NEJM) in May 2025.

The safety profile of Libtayo as adjuvant treatment of patients with CSCC at high risk of recurrence after surgery and radiation is consistent with the known safety profile for Libtayo monotherapy in advanced cancers. In the trial, adverse events (AEs) occurred in 91% of patients receiving Libtayo (n=205) and 89% of patients receiving placebo (n=204). 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 who received Libtayo were fatigue, pruritus, rash, diarrhea, arthralgia, hypothyroidism and maculo-papular rash. The only grade ≥3 AE that occurred in more than 2% of patients in the Libtayo arm was hypertension. AEs led to permanent discontinuation of treatment in 10% of patients who received Libtayo and 2% of patients who received placebo. Two patients in each arm experienced an AE leading to death.

About the Phase 3 Trial
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.

About CSCC
Cutaneous squamous cell carcinoma (CSCC) is a type of non-melanoma skin cancer (NMSC), and one of the most common cancers in the world. In the EU, the incidence of NMSC overall is expected to increase by 40% by 2040. CSCC can often be treated successfully with surgery, but many patients may have a "high risk" form that is more aggressive, and they face an increased risk of recurrence and disease progression.

(Press release, Regeneron, OCT 17, 2025, View Source [SID1234656777])