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.

•
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.

•
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.

•
Predicted radiation reduction and visual preservation

•
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.

•
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.

•
Improved visual acuity during neoadjuvant treatment

•
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.

•
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.

•
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.

•
Safety and Tolerability:

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

•
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])

On October 17, 2025 Merck, a leading science and technology company, reported the presentation of longer-term results from the global Phase 3 MANEUVER trial evaluating pimicotinib, an investigational colony stimulating factor-1 receptor (CSF-1R) inhibitor in development by Abbisko Therapeutics Co., Ltd., for the treatment of patients with tenosynovial giant cell tumor (TGCT). This latest analysis showed that, with a median follow-up of 14.3 months, the objective response rate (ORR) for people treated with pimicotinib from the beginning of the study increased considerably to 76.2% (95% CI: 63.8, 86.0) by blinded independent review committee (BICR) per RECIST v1.1, from 54% at Week 25. The study also showed continued clinically meaningful improvements in key secondary endpoints related to patient outcomes such as pain and function. The safety profile was consistent with previously reported data. The results are being presented today in the Sarcoma mini-oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 (Presentation # 2690MO).

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"With the initial results of the global MANEUVER study presented earlier this year at ASCO (Free ASCO Whitepaper), pimicotinib demonstrated the highest objective response rate seen in a Phase 3 clinical trial of a systemic therapy in TGCT," said Prof. Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. "These latest findings build on those impressive results, showing that these tumor responses not only persist but deepen over time. Importantly, we also see continued improvements beyond one year in the patient-reported symptoms and functional outcomes that truly make a difference in patients’ abilities to go about their daily lives. Together, these findings indicate the potential for pimicotinib to be a best-in-class systemic treatment for patients with TGCT."

"TGCT causes pain, stiffness, and loss of range of motion, affecting patients’ ability to participate in activities of daily living and with their families or communities. Ultimately, this affects everyone and takes a mental and physical toll," said Sydney Stern, PhD, MS, TGCT Support, a Program of the Life Raft Group. "Patients benefit from more options that address their symptoms and shrink the disease. Importantly, addressing their symptoms enables patients to be the parents, partners, carers, and people they want to be without wondering when their TGCT will take over their life again."

The latest analysis of the global Phase 3 MANEUVER trial includes results from 63 patients who received pimicotinib for 24 weeks in Part 1 and then continued on pimicotinib in the open-label phase of the trial. With a median follow-up of 14.3 months, tumor responses continued to improve:

ORR per BIRC based on RECIST v1.1 increased to 76.2% (95% CI: 63.8, 86.0), from 54% at Week 25.
ORR per BIRC based on tumor volume score (TVS), an endpoint designed specifically for TGCT, increased to 74.6% (95% CI: 62.1, 84.7), from 61.9% at Week 25.
At the time of the data cutoff, the median duration of response was not reached (range: 0.03-19.81 months), with 93.7% of pimicotinib-treated patients experiencing a reduction in tumor size by BIRC per RECIST v1.1 at longer-term follow up.
Pimicotinib also demonstrated clinically meaningful improvements with longer-term follow-up up to week 73 in key patient-reported measures including range of motion, pain, stiffness and physical function that significantly impact people living with TGCT:

For relative range of motion, pimicotinib showed a mean change from baseline of 23.9% (increased from 15.6% at week 25).
Mean change from baseline continued to show improvements in physical function as measured by the patient-reported PROMIS-PF scale, and reductions in stiffness and pain as measured by the Worst Stiffness Numeric Scale Rating and Brief Pain Inventory worst pain rating, respectively.
The analysis also includes results for patients who were initially randomized to receive placebo in Part 1, then switched to pimicotinib in the open label part of the study (n=31). These patients experienced a clear benefit from pimicotinib treatment, with an ORR of 64.5% both by BICR per RECIST v1.1 and by TVS with a median follow-up of 8.5 months after switching to pimicotinib.

At longer-term follow-up, in patients who had received pimicotinib throughout the study, there were no new safety signals, and no evidence of cholestatic hepatotoxicity, drug-induced liver injury or hair/skin hypopigmentation. Most treatment-emergent adverse events remained mild in severity and were manageable.

"These longer-term results highlight the potential of pimicotinib to transform care by providing a systemic therapy that delivers meaningful, lasting benefit not only in terms of reducing tumor burden but in helping patients regain function and live with reduced pain," said Victoria Zazulina, M.D., Head of Development Unit, Oncology, Healthcare business of Merck. "Guided by this robust global study—conducted across North America, Europe and China—we are working with regulatory authorities as we seek to make this treatment available to patients as quickly as possible."

An application for marketing authorization of pimicotinib as a Class 1 innovative drug for adult patients with TGCT has been accepted for review by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA). Additional applications are planned in the U.S. and other markets around the world.

About MANEUVER

The pivotal global Phase 3 MANEUVER study is a three-part, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pimicotinib in patients with TGCT who require systemic therapy and have not received prior anti-CSF-1/CSF-1R therapy. The study is being conducted by Abbisko Therapeutics in China (n=45), Europe (n=28), and the U.S. and Canada (n=21).

In the double-blind Part 1, 94 patients were randomized 2:1 to receive either 50 mg QD of pimicotinib (n=63) or placebo (n=31) for 24 weeks. The primary endpoint was objective response rate (ORR) at week 25, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR) in the intent-to-treat (ITT) population. Secondary endpoints include tumor volume score (TVS), relative range of motion, stiffness by Numeric Rating Scale (NRS), pain by Brief Pain Inventory (BPI), and physical function measured by Patient-Reported Outcomes Measurement Information System (PROMIS-PF).

After the double-blind Part 1, eligible patients could continue to the open-label Part 2 for up to 24 weeks of further treatment. Patients who completed Part 2 could then enter the open-label extension phase (Part 3) for extended treatment and safety follow-up.

About Pimicotinib (ABSK021)

Pimicotinib (ABSK021), which is being developed by Abbisko Therapeutics, is a novel, orally administered, highly selective and potent small-molecule inhibitor of CSF-1R. Pimicotinib has been granted breakthrough therapy designation (BTD) for the treatment of inoperable TGCT by China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA), and priority medicine (PRIME) designation from the European Medicines Agency (EMA). Merck holds worldwide commercialization rights for pimicotinib.

Advancing the Future of Cancer Care

At Merck, we strive every day to improve the futures of people living with cancer. Building on our 350-year global heritage as pharma pioneers, we are focusing our most promising science to target cancer’s deepest vulnerabilities, pursuing differentiated molecules to strike cancer at its core. By developing new therapies that can help advance cancer care, we are determined to create a world where more cancer patients will become cancer survivors. Learn more at www.merckgroup.com.

(Press release, Merck & Co, OCT 17, 2025, View Source [SID1234656763])

On October 17, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported the expansion of its Phase III clinical development program of the novel, potential first-in-class investigational bispecific antibody, ivonescimab, into colorectal cancer (CRC) with the initiation of the global Phase III HARMONi-GI3 trial.

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Summit is starting a Phase III clinical study, HARMONi-GI3, to evaluate ivonescimab plus chemotherapy compared to bevacizumab plus chemotherapy as first line therapy in patients with unresectable metastatic colorectal cancer (CRC).

Clinical trial sites for HARMONi-GI3 are planned to begin activating in the United States prior to the end of the year. The multiregional study intends to enroll approximately 600 patients. The primary endpoint for this study is progression-free survival.

Each year, approximately 48,000 patients are estimated to be diagnosed with or have unresectable recurrent metastatic MSS CRC (also known as mismatch repair-proficient colorectal cancer, or pMMR CRC).1 There have been limited options approved in the United States in the last 20 years for those first-line patients whose tumors are not positive for certain biomarkers or other activating mutations.

MSS CRC is a setting where monoclonal PD-1 inhibitors such as pembrolizumab and nivolumab have failed to show a clinically meaningful benefit. Anti-VEGF therapy (e.g., bevacizumab) plus chemotherapy is the standard of care for many patients with 1L metastatic MSS CRC.

At the 2024 Annual Congress of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) (ESMO 2024), Akeso Inc. (Akeso) presented encouraging Phase II data of ivonescimab in combination with FOLFOXIRI chemotherapy demonstrating an objective response rate (ORR) of 81.8% (95% CI: 59.7% – 94.8%) and a disease control rate (DCR) of 100% (95% CI: 84.6% – 100.0%) in 22 patients. This Phase II study, AK112-206, was conducted in China and sponsored by Akeso with all relevant data exclusively generated, managed, and analyzed by Akeso. In the ivonescimab plus FOLFOXIRI chemotherapy arm, there were no treatment emergent adverse events that led to permanent discontinuation of ivonescimab as of the data cutoff from the ESMO (Free ESMO Whitepaper) 2024 presentation.

Subsequently, AK112-206 was expanded to include additional patients from the United States and China to study ivonescimab in combination with FOLFOX chemotherapy. FOLFOX in combination with a monoclonal antibody such as bevacizumab represents a preferred treatment regimen for physicians treating patients in the United States and other western territories. The data from the initial patient cohort presented at ESMO (Free ESMO Whitepaper) 2024 have continued to mature, in addition to the global Phase II data generated in combination with FOLFOX in the United States and China, which support the Phase III HARMONi-GI3 study design using FOLFOX.

"As promised earlier in the year, we sought to expand the ivonescimab clinical development program beyond non-small cell lung cancer in order to continue to explore the potential benefits of its specifically-engineered, novel design and mechanism of action, including its cooperative binding attributes," stated Robert W. Duggan and Dr. Maky Zanganeh, Co-Chief Executive Officers of Summit. "Microsatellite stable colorectal cancer represents a global unmet need whereby ivonescimab has the potential to bring the benefits of immunotherapy to solid tumors where PD-1 monoclonal antibodies have not been able to successfully improve upon existing standards of care. We are thrilled by the potential of ivonescimab to make a significant difference to these patients with few front-line options available today."

Conference Call

Summit Therapeutics Inc. will host a conference call and live webcast to discuss recent updates related to ivonescimab, including data released at ESMO (Free ESMO Whitepaper), on Monday, October 20, 2025, at 8:00am ET. Conference call and webcast information will be accessible through our website www.smmttx.com.

An archived edition of the webcast will be available on our website later in the day on Monday.

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multi-fold higher affinity to PD-1 when in the presence of VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al., SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al., SITC (Free SITC Whitepaper), 2023) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 3,000 patients have been treated with ivonescimab in clinical studies globally.

Summit began its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In early 2025, the Company began enrolling patients in the United States for HARMONi-7. Summit intends to open clinical trial sites in the United States for the Phase III study in colorectal cancer (CRC) by the end of 2025.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a 3rd generation EGFR TKI (e.g., osimertinib). Enrollment in HARMONi was completed in the second half of 2024, top-line results were announced in May of 2025, with detailed results provided in September 2025.

HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression.

HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

HARMONi-GI3 is a planned Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC.

In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

Akeso is actively conducting multiple Phase III clinical studies in settings outside of NSCLC, including biliary tract cancer, colorectal cancer, breast cancer, pancreatic cancer, small cell lung cancer, and head and neck cancer.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (FDA) for the HARMONi clinical trial setting.

(Press release, Summit Therapeutics, OCT 17, 2025, View Source [SID1234656762])