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])

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 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported updated data from the Phase 1b/2 study of palazestrant in combination with ribociclib in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. These findings will be presented in a poster session on October 20 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany.

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"We are very pleased with these latest data showing compelling progression-free survival and favorable tolerability of palazestrant plus ribociclib, further reinforcing this regimen’s potential as a new standard of care in metastatic breast cancer," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "These data showcase the activity of the combination in both ESR1 mutant and wild-type tumors, an important component for effective frontline treatment, and underscore the importance of complete ER antagonism in the treatment of ER-positive breast cancer. As we work to transform the breast cancer treatment paradigm, we are increasingly confident in palazestrant’s potential to become a best-in-class, backbone endocrine therapy and are excited to now have our second Phase 3 trial, OPERA-02, underway evaluating palazestrant with ribociclib in the frontline setting."

Key Findings from the Phase 1b/2 Study of Palazestrant in Combination with Ribociclib
As of July 8, 2025, 72 patients were enrolled across the 90 mg and 120 mg palazestrant dose cohorts. 56 patients received 120 mg once-daily palazestrant and 16 patients received 90 mg once-daily palazestrant, all with the approved dose of ribociclib for metastatic breast cancer of 600 mg daily. 45 (63%) patients had prior treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy for advanced disease. 33% (15/45) of patients who had prior treatment with CDK4/6i in the advanced setting (2/3L) had an ESR1 mutation at baseline.

Efficacy

In the 90 mg palazestrant dose cohort, with a median follow-up of 10.8 months, median progression-free survival (PFS) was not reached.
In the 120 mg palazestrant dose cohort, with a median follow-up of more than 19 months, median PFS are mature. Median PFS was 15.5 months for all patients. Median PFS was 12.2 months for those who received prior treatment with CDK4/6i, including 9.2 months for patients with ESR1 wild-type tumors and 13.8 months for patients with tumors with ESR1 mutations.

Safety and Pharmacokinetics

Across 72 patients treated, 90 mg or 120 mg of palazestrant combined with 600 mg of ribociclib daily was well tolerated with no new safety signals or increase in toxicity.
Palazestrant and ribociclib did not demonstrate any drug-drug interactions and the overall safety profile was consistent with the established safety profile of ribociclib plus an endocrine therapy.
The majority of treatment-emergent adverse events were grade 1 or 2, and the severity and incidence of adverse events were consistent with the expected safety profile of each drug.

"Despite recent advances in the treatment of ER+/HER2- metastatic breast cancer, there remains a significant need for therapies that can overcome endocrine resistance, particularly following treatment with a CDK4/6 inhibitor," said Dr. Nancy Lin, Associate Chief of the Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, at the Dana-Farber Cancer Institute. "I am very encouraged by these new data showing the novel palazestrant-ribociclib combination compares favorably to other endocrine therapy-CDK4/6 inhibitor combinations. With a compelling median PFS in the challenging post-CDK4/6 inhibitor setting, I believe palazestrant has the potential to serve as an important combination agent in the metastatic setting."

Poster Presentation Details
Title: Palazestrant (OP-1250) plus ribociclib in patients with estrogen receptor-positive,
human epidermal growth factor receptor 2-negative (ER+, HER2-) advanced breast cancer (ABC)
Poster Number: 502P
Session: Breast Cancer, Metastatic Session
Date/Time: Monday, October 20, 2025, from 12:00-12:45pm CEST / 6:00-6:45am ET

Additional information can be found on the ESMO (Free ESMO Whitepaper) 2025 website, including abstracts. A copy of the poster will be made available on the Publications page of Olema’s website in alignment with the ESMO (Free ESMO Whitepaper) 2025 embargo policy.

(Press release, Olema Oncology, OCT 18, 2025, View Source [SID1234656776])