On October 18, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive results from the Phase III evERA Breast Cancer study. Data showed giredestrant in combination with everolimus significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 44% and 62% in the intention-to-treat (ITT) and ESR1-mutated populations, respectively, compared with standard-of-care endocrine therapy plus everolimus. The evERA study is evaluating the investigational giredestrant combination in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy. This is the first positive head-to-head Phase III trial investigating a selective estrogen receptor degrader-containing regimen versus a standard-of-care combination. The results are being presented in an oral session at the European Society for Medical Oncology Congress 2025. Data will be shared with health authorities, with the aim of bringing this potential treatment option to people as soon as possible.

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"A particularly high unmet need remains for people who become resistant to endocrine therapies and CDK inhibitors. These study results support the potential for the giredestrant combination to become a new standard-of-care for all patients in this setting," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development.

"Resistance to standard-of-care therapies is common in the post-CDK inhibitor setting, and the results from evERA validate using a combination to address this challenge," said Erica L. Mayer, M.D., Medical Oncologist at Dana-Farber Cancer Institute. "The clinically meaningful benefit observed with the giredestrant and everolimus all-oral combination is impressive and speaks to its potential to improve outcomes for patients in need of new treatment options."

The giredestrant combination demonstrated a statistically significant and clinically meaningful improvement in PFS compared with standard-of-care endocrine therapy plus everolimus. In the ITT population, the median PFS was 8.77 months compared with 5.49 months in the giredestrant and comparator arm, respectively (stratified hazard ratio [HR]=0.56; 95% CI: 0.44-0.71, p-value= <0.0001). In the ESR1-mutated population, the median PFS was 9.99 months compared with 5.45 months in the giredestrant and comparator arm, respectively (HR=0.38; 95% CI: 0.27-0.54, p-value= <0.0001). The PFS benefit was consistent across pre-specified subgroups in both populations. Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed in the ITT (HR=0.69, 95% CI: 0.47-1.00, p-value=0.0473) and ESR1-mutated populations (HR=0.62, 95% CI: 0.38-1.02, p-value=0.0566). Follow-up for OS will continue to next analysis. Giredestrant in combination with everolimus also demonstrated improvements in key secondary endpoints (objective response rate and duration of response) compared with the comparator arm across both patient populations.

Adverse events for the giredestrant-based combination were manageable and consistent with the known safety profiles of the individual medicines. No new safety signals were observed, including no photopsia.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. Resistance to endocrine therapies, particularly in the post-CDK inhibitor setting, increases the risk of disease progression and is associated with poor outcomes. All-oral combination therapies, such as giredestrant plus everolimus, could address this by targeting two different signaling pathways while helping to minimize the impact of treatment on people’s lives without the need for injections.

Our extensive giredestrant clinical development program spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.

About the evERA Breast Cancer study

evERA Breast Cancer [NCT05306340] is a Phase III, randomized, open-label, multicenter study evaluating the efficacy and safety of giredestrant in combination with everolimus versus standard-of-care endocrine therapy in combination with everolimus in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have had previous treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.

The co-primary endpoints are investigator-assessed progression-free survival in the intention-to-treat and ESR1-mutated populations, defined as the time from randomization to the time when the disease progresses or a patient dies from any cause. The trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to 40% of people with ER-positive disease have ESR1 mutations. Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and safety.

About estrogen receptor (ER)-positive breast cancer

Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year. Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. A defining feature of ER-positive breast cancer is that its tumor cells have receptors that attach to estrogen, which can contribute to tumor growth.

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity. Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy. There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

About giredestrant

Giredestrant is an investigational oral, next-generation selective estrogen receptor degrader (SERD) and full antagonist.

Giredestrant is designed to block estrogen from binding to the estrogen receptor (ER), triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.

Giredestrant has an extensive clinical development program and is being investigated in five company-sponsored Phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)
Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)
Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)
Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)
Giredestrant plus dual HER2 blockade versus dual HER2 blockade in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)

(Press release, Genentech, OCT 18, 2025, View Source [SID1234656757])

On October 18, 2025 Alphamab Oncology (Stock Code: 9966.HK) reported that the first interim analysis results of a phase III clinical trial of anbenitamab injection (KN026), independently developed by the Company and co-developed with JMT-Bio Technology Co., Ltd., a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. (stock code: 1093.HK), in combination with chemotherapy as second-line or above treatment of HER2-positive gastric cancer (GC) (including gastroesophageal junction cancer (GEJ)) (Study ID: KN026-001, also known as KC-WISE), have been presented at the 2025 European Society for Medical Oncology Congress (ESMO Congress 2025) Late-Breaking Abstract (LBA) Oral Presentation Session.

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LBA Oral Presentation Session is a highly anticipated global highlight of the ESMO (Free ESMO Whitepaper) Congress. The research presented in this category is both highly topical and of significant clinical value. Their findings often herald potential impacts on current clinical practice and can even guide the future direction of entire therapeutic fields.

Title：KN026 in combination with chemotherapy for previously treated HER2-positive gastric or gastroesophageal carcinomas (GC/GEJC): Interim analysis of KC-WISE

Number: LBA 78

Speaker: Jianming Xu, Chinese PLA General Hospital

Date：Friday, 17 October 2025

METHODS

Enrolled patients in study KN026-001 (KC-WISE) with HER2-positive GC/GEJ who had disease progression after trastuzumab-based therapy were randomized to receive either anbenitamab (KN026) in combination with chemotherapy (the "Anbenitamab Group") or chemotherapy with placebo (the "Control Group"). The patients were stratified based on (i) type of chemotherapy, (ii) HER2 expression level, and (iii) number of prior lines of treatments.

RESULTS

At baseline, patient characteristics were generally well balanced between the two groups. The median age was approximately 64 in the Anbenitamab Group and 61 in the Control Group. In both groups, over 80% of patients had an ECOG PS of 1, and nearly all patients were diagnosed with stage IVB disease at enrollment. All patients had previously received chemotherapy, most commonly taxanes (over 70%), with the remainder receiving irinotecan-based regimens.

As of April 3, 2025, the median follow-up duration was 9.7 months (95% CI, 7.2 to 11.9 months) in the Anbenitamab Group and 9.8 months (95% CI, 7.4 to 12.9 months) in the Control Group.

Efficacy as assessed by the Independent Review Committee (IRC):

● The median treatment-related adverse event (PFS) for the Anbenitamab Group was 7.1 months, compared with 2.7 months in the Control Group. The hazard ratio (HR) is 0.25 (P value is 5.44 × 10⁻¹²), corresponding to a 75% reduction in the risk of disease progression or death.

● The median overall survival (OS) for the Anbenitamab Group was 19.6 months (not mature), compared with 11.5 months in the Control Group. The HR is 0.29, representing a 71% reduction in the risk of death, and P value is 1.56 × 10⁻6, which is well below the prespecified extremely stringent alpha threshold of 0.00001.

● The objective response rate (ORR) was 55.8% in the Anbenitamab Group versus 10.8% in the Control Group, while the disease control rate (DCR) was 80.0% and 41.9%, respectively. The median duration of response (DoR) was 8.2 months and 2.9 months, respectively.

Safety:

● The median treatment duration was 6.5 cycles in the Anbenitamab Group and 3.0 cycles in the Control Group.

● The incidence of Grade 3 treatment-emergent adverse events (TEAEs) or above was 60.6% in the Anbenitamab Group and 51.6% in the Control Group, while the incidence of serious adverse events (SAEs) was 31.9% and 33.3%, respectively.

● The most frequently observed Grade 3 treatment-related adverse events (TRAEs) or above in the Anbenitamab Group included neutropenia (29.8%), leukopenia (21.3%), anemia (18.1%), diarrhea (8.5%) and asthenia (8.5%), while the most frequently observed Grade 3 TRAEs or above in the Control Group included leukopenia (24.7%), neutropenia (21.5%), anemia (10.8%), diarrhea (7.5%) and thrombocytopenia (5.4%). The incidence of cardiotoxicity in both groups were both 3.2%, indicating fewer cardiac concerns.

CONCLUSIONS

The interim analysis demonstrated that anbenitamab achieved superior efficacy in second-line or third-line HER2-positive gastric cancer patients who had been previously treated with trastuzumab. The study met both its primary endpoints of PFS and OS with statistically significant and clinically meaningful improvements, indicating its potential to change clinical practice guidelines for the treatment of second-line or above gastric cancer. Compared with the recently published DESTINY-Gastric04 results of DS-8201 in second-line gastric cancer, anbenitamab demonstrates potential advantages in both efficacy and safety.

Prompted by these encouraging results of anbenitamab, we are preparing to expand clinical development into first-line and perioperative gastric cancer through new registrational trials, aiming to extend benefits to more patients. Meanwhile, JSKN003, an ADC built upon KN026, has demonstrated high-security profile and distinctive advantages. With multiple registrational studies currently advancing as planned, we anticipate even more outstanding performance from JSKN003 in the future.

About Anbenitamab (KN026)

Anbenitamab (KN026) is an anti-HER2 bispecific antibody independently developed by Alphamab Oncology using the proprietary Fc-based heterodimer bispecific platform technology called CRIB (Charge Repulsion Induced Bispecific). KN026 can simultaneously bind two non-overlapping epitopes of HER2, resulting in HER2 signal blockade.

Results from multiple clinical studies showed that KN026 has promising efficacy for the treatment of HER2-positive solid tumors, both in the first-line and in patients previously treated with trastuzumab. Currently, several pivotal trials of KN026 for second-line or above HER2-positive GC/gastroesophageal junction cancer (GEJ), first-line HER2-positive BC, neoadjuvant treatment of HER2-positive BC are being conducted. KN026 for the treatment of patients with HER2-positive GC who have failed first-line standard treatment was granted breakthrough therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA). KN026 for the treatment of HER2-positive or low expressing GC was granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA). In September 2025, the first New Drug Application (NDA) for anbenitamab injection has been accepted by the NMPA for use in combination with chemotherapy in patients with HER2-positive locally advanced, recurrent, or metastatic GC/GEJ who have failed at least one prior systemic therapy (which must include trastuzumab in combination with chemotherapy).

In August 2021, the Company entered an agreement with JMT-Bio Technology Co., Ltd. ("JMT-Bio"), a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (stock code: 1093.HK), for the development and commercialization of KN026 in Mainland China. JMT-Bio was granted exclusive license rights of KN026 for the development and commercialization in the indications of BC an GC/GEJ in Mainland China (excluding Hong Kong, Macau and Taiwan).

(Press release, Alphamab, OCT 18, 2025, View Source [SID1234656997])

On October 18, 2025 NuCana plc (NASDAQ: NCNA) ("NuCana" or the "Company") reported data at the European Society for Medical Oncology Congress 2025 ("ESMO") on a new model system investigating the synergistic effects of NUC-7738 and PD-1 inhibition in primary organoids derived from patients with renal cell carcinoma ("RCC").

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Using patient-derived organoids ("PDOs") from ten patients with RCC and autologous tumor-infiltrating lymphocytes ("TILs"), co-culture experiments reveal that NUC-7738 enhances the effectiveness of PD-1 inhibitors, resulting in increased tumor cell killing. This combinatorial approach may offer a new option for cancers that no longer respond to anti-PD-1 therapy by targeting multiple aspects of the tumor microenvironment through the disruption of RNA polyadenylation and subsequent changes in cancer cell gene expression.

The data presented at ESMO (Free ESMO Whitepaper) reinforces the mechanism of action for NUC-7738 as observed in the ongoing Phase 1/2 NuTide:701 clinical study. Data to date from NuTide:701 have demonstrated a favorable safety profile, meaningful tumor volume reduction, and prolonged progression-free survival in patients with PD-1 inhibitor refractory and resistant metastatic melanoma.

Andrew Kay, NuCana’s Executive Chairman said: "We are excited to share these new data on NUC-7738 in combination with PD-1 inhibitors in a real-time organoid model system. In addition to demonstrating clear benefits of combining PD-1 inhibitors with NUC-7738, similar to those seen in patients on the ongoing NuTide:701 study, this may lead to robust, patient-specific testing for a selection of immune checkpoint therapies."

Mr. Kay continued: "The translational data that has been generated in this study increases our confidence that the effects we are seeing are a result of NUC-7738 targeting multiple aspects of the tumor microenvironment and increasing PD-1 inhibition. Our data on mechanism of action of NUC-7738 indicate that the phenomena are not restricted to a single tumor type, and that NUC-7738 may have the ability to sensitize many cancers to PD-1 inhibitor therapy."

Based on the exciting initial data from the Phase 1/2 NuTide:701 clinical study, regulators have approved the expansion of the study to recruit an additional 28 patients with PD-1 inhibitor-resistant melanoma. NuCana is currently recruiting patients to this expansion study and plans to meet with the U.S. Food and Drug Administration to discuss the data from this study to determine the optimal registration strategy to support marketing approval.

The details of NuCana’s presentation at ESMO (Free ESMO Whitepaper) are as follows:

Abstract Title: Patient Derived Organoids Reveal Synergy Between NUC-7738 and PD-1 Inhibition in Renal Cell Cancer
Poster Number: 1530P
Session: Investigational Immunotherapy
Date: Sunday, October 19, 2025
Presenting Author: H. Abdullah

(Press release, Nucana, OCT 18, 2025, View Source [SID1234656774])

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 18, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, reported the presentation of new clinical data from its first-in-human Phase 1a study of NX-1607, a first-in-class oral inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) in patients with relapsed/refractory solid tumors. The data are being presented at the European Society for Medical Oncology Congress (ESMO 2025), taking place October 17–21, 2025, in Berlin, Germany.

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"As a first-in-class oral inhibitor of CBL-B, NX-1607 may offer a novel therapeutic approach to treat solid tumors by targeting a previously unaddressed pathway in immune regulation affecting not only T cells, but also multiple immune cell types, including dendritic cells and natural killer cells, which all play critical roles in the tumor microenvironment," said Paula O’Connor, M.D., chief medical officer of Nurix. "These data highlight NX-1607’s activity as an immuno-oncology agent, showing promising signs of biologic activity and clinical benefit, and supporting its continued development as an innovative next generation checkpoint inhibitor therapy designed to improve outcomes for cancer patients."

In a poster titled: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, data were presented from a total of 82 patients with eleven different tumor types treated across six once-daily (QD) and five twice-daily (BID) dosing regimens ranging from 5 mg to 80 mg total daily dose. Patients were heavily pre-treated with a median of 3 prior regimens including a median of 1 prior chemo/immunotherapy regimen. NX-1607 demonstrated dose-dependent exposure, increases in proximal and distal biomarkers, evidence of peripheral immune activation, and reductions in tumor volume and cancer biomarkers. Despite the advanced stages of disease and the broad range of tumor types included in the trial, NX-1607 demonstrated evidence of clinical activity including reductions in tumor-specific biomarkers (prostate-specific antigen (PSA) in prostate cancer and carcinoembryonic antigen (CEA) in colorectal cancer), long-term stable disease, and a confirmed partial response in a patient with micro-satellite stable colorectal cancer (MSS CRC), a tumor type typically unresponsive to immune checkpoint therapy. As of the 26 July 2025 data cut, 71 patients were evaluable for response, with a disease control rate (DCR) of 49.3%. With respect to duration of response, 7 patients achieved either stable disease (SD) or partial response (PR) for ≥5 months on treatment and 1 patient with MSS CRC achieved a PR and was treated for 27 months. Further supporting the dose-dependent activity of NX-1607, the greatest reductions in PSA among the prostate cancer patients were achieved in the BID dosing groups with 6/13 patients having PSA reductions of ≥50%.

NX-1607 was shown to be tolerable at pharmacologically active doses and has a safety profile comparable to approved immuno-oncology agents, with most adverse events Grade 2 or less in severity. Immune-related adverse events were observed in 6 patients, indicating on-target immune activation, similar to what is observed with PD-1/PD-L1 therapies. The most common treatment emergent adverse events included nausea and vomiting, which were mitigated by both BID dosing and the introduction of a step-up dosing regimen where patients were initially treated at lower doses and increased to the target dose during the first cycle of treatment.

"NX-1607 has demonstrated potent single agent activity preclinically and now most importantly, we see clear signals of anti-tumor activity in patients with advanced disease. The results are particularly intriguing in MSS colorectal cancer and metastatic prostate cancer, two important indications where current immunotherapies have failed to demonstrate efficacy," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "We look forward to further exploring the broad therapeutic potential of NX-1607 while we advance our lead asset bexobrutideg, an oral BTK degrader, into pivotal trials in patients with relapsed or refractory chronic lymphocytic leukemia."

About NX-1607
NX-1607 is an investigational first-in-class oral inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) being developed for immuno-oncology indications, including a range of solid tumor types. CBL-B is a cytoplasmic E3 ubiquitin ligase that negatively regulates T cell activation, making it an attractive target for immuno-oncology and offering a novel therapeutic approach to treat solid tumors. Inhibition of CBL-B in preclinical studies reverses T cell exhaustion, alleviates tumor-induced immunosuppression, and may also exert direct antitumor effects. Nurix is evaluating NX-1607 in an ongoing Phase 1 trial in adults in a range of oncology indications. This study includes a thorough investigation of both dose and schedule in the Phase 1a portion. Additional information on the NX-1607 clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).

(Press release, Nurix Therapeutics, OCT 18, 2025, View Source [SID1234656775])