On October 19, 2025 Taiho Pharmaceutical Co., Ltd. ("Taiho") and Arcus Biosciences, Inc. (NYSE:RCUS, "Arcus") reported that Taiho exercised its option to develop and, if approved, commercialize casdatifan (International Nonproprietary Name; development code: AB521), an investigational small molecule HIF (Hypoxia Inducible Factor)-2α inhibitor, in Japan and certain other territories in Asia (excluding mainland China). This option exercise is based on a 2017 option and license agreement between Taiho and Arcus. This is the fifth option exercise by Taiho to an Arcus program.

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In exchange for the exclusive license to casdatifan, Taiho will make an option exercise payment, as well as additional payments upon achievement of clinical, regulatory and commercialization milestones, and, if any products from the program are approved, will pay royalties on net sales of such products.

Casdatifan is an investigational small molecule compound developed by Arcus. Arcus is currently conducting an ongoing global, registrational Phase 3 study, PEAK-1,* comparing the combination therapy of casdatifan and a VEGFR-targeted tyrosine kinase inhibitor (TKI) to monotherapy using a VEGFR-targeted TKI alone in patients with clear cell renal cell carcinoma (ccRCC). Japan is also expected to participate in the study starting in the first half of 2026.

*PEAK-1: A Randomized, Placebo-Controlled, Double-Blind, Multicenter Phase 3 Trial of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients with Advanced Clear Cell Renal Cell Carcinoma

Through this collaboration, Taiho and Arcus are committed to delivering casdatifan as a potentially innovative new medicine to patients and healthcare professionals as swiftly as possible.

About Casdatifan (AB521)

Casdatifan is a small-molecule inhibitor of HIF-2α, a master switch that turns on hundreds of genes in response to low oxygen levels; when oxygen levels return to normal, HIF-2α is turned off. In a majority of people with the most common form of kidney cancer (clear cell renal cell carcinoma), this shut-off mechanism is deficient and HIF-2α remains activated even in the presence of oxygen, causing normal kidney cells to become cancerous. Casdatifan is designed to provide deeper and more durable inhibition of the HIF-2α pathway.

About clear cell renal cell carcinoma (ccRCC)

Kidney cancer is a disease with a rising worldwide incidence estimated at 400,000 new cases annually, and a worldwide mortality rate approaching 175,000 deaths per year. Current projections suggest incidence continuing to increase over the next decade, emphasizing the urgency of addressing this significant global health trend. ccRCC is the most common type of kidney cancer in adults, making up 75-80% of all cases.

(Press release, Taiho, OCT 19, 2025, View Source [SID1234656800])

On October 19, 2025 Astrazeneca and Daiichi Sankyo reported positive results from the TROPION-Breast02 Phase III trial showed Datroway (datopotamab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement for the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to investigator’s choice of chemotherapy as 1st-line treatment for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option.

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These late-breaking results will be presented today during a Proffered Paper session at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Berlin, Germany (abstract #LBA21).

Datroway demonstrated a 5.0-month improvement in median OS compared to chemotherapy (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.64-0.98; p=0.0291). Median OS was 23.7 months for patients treated with Datroway versus 18.7 months for those treated with chemotherapy.

Datroway reduced the risk of disease progression or death by 43% compared to chemotherapy (HR 0.57; 95% CI 0.47-0.69; p<0.0001) as assessed by blinded independent central review (BICR). Median PFS was 10.8 months for patients treated with Datroway versus 5.6 months for those treated with chemotherapy.

In addition to patients whose tumours did not express PD-L1, TROPION-Breast02 enrolled patients with PD-L1 expressing tumours for whom immunotherapy was not an option due to other factors.

Rebecca Dent, MD, FRCP, Professor and Deputy Chief Executive Officer, National Cancer Centre Singapore, and principal investigator for the trial, said: "In TROPION-Breast02, datopotamab deruxtecan meaningfully extended patients’ lives and nearly doubled their time without disease progression. These are significant outcomes for patients with metastatic triple-negative breast cancer who are not suitable candidates for immunotherapy, and remarkable results considering the trial included a subset of patients with highly aggressive disease who are often excluded from research in this setting."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "The TROPION-Breast02 results show for the first time that these triple-negative breast cancer patients may have an alternative to chemotherapy in the 1st-line setting that can both delay the progression of their disease and prolong their lives. For Datroway to have so significantly improved patient outcomes in the 1st-line metastatic setting as monotherapy also gives us great confidence in its potential in combination with Imfinzi, and in the early-stage, potentially curative setting where our next studies are ongoing."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "Patients with metastatic triple-negative breast cancer have one of the worst prognoses of any breast cancer subtype, and for those who are not candidates for immunotherapy, chemotherapy has long been the 1st-line standard of care. The TROPION-Breast02 results show Datroway has the potential to replace traditional chemotherapy in this setting and to meaningfully improve survival of patients."

Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Summary of efficacy results

Datroway (n=323)

ICC (n=321)

Median OS, months (95% CI)

23.7 (19.8-25.6)

18.7 (16.0-21.8)

HR (95% CI)

0.79 (0.64-0.98)

p-value

0.0291

Median PFS by BICR, months (95% CI)

10.8 (8.6-13.0)

5.6 (5.0-7.0)

HR (95% CI)

0.57 (0.47-0.69)

p-value

<0.0001

Median PFS by investigator, months (95% CI)

9.6 (7.4-11.2)

5.2 (4.2-5.6)

HR (95% CI)

0.56 (0.47-0.67)

Confirmed ORR, %

62.5

29.3

CR, % (n)

9.0 (29)

2.5 (8)

PR, % (n)

53.6 (173)

26.8 (86)

Median DoR, months (95% CI)

12.3 (9.1-15.9)

7.1 (5.6-8.9)

As of 25 August 2025, data cut-off, 45 patients (14%) remained on Datroway and 8 patients (3%) on chemotherapy.
BICR, blinded independent central review; CI, confidence interval; CR, complete response; DoR, duration of response; HR, hazard ratio; ICC, investigator’s choice of chemotherapy; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response

Patients receiving Datroway were on treatment more than twice as long as those receiving chemotherapy (median duration of treatment of 8.5 versus 4.1 months) and experienced a lower rate of treatment-related adverse events (TRAEs) associated with discontinuation (4% versus 7%). Grade 3 or higher TRAEs occurred in 33% and 29% of patients in the Datroway and chemotherapy arms, respectively. The most common Grade 3 or higher TRAEs were neutropenia (3%, 13%), stomatitis (8%, 0%), leukopenia (<1%, 4%), fatigue (3%, 3%), vomiting (1%, <1%), anaemia (2%, 3%), alopecia (0%, <1%), peripheral neuropathy (0%, 2%), dry eye (1%, 0%), nausea (<1%, <1%), decreased appetite (<1%, <1%) and constipation (<1%, 0%). There was one Grade 5 interstitial lung disease (ILD) event in the Datroway arm adjudicated as drug-related by an independent committee. This event was characterised as Grade 3 pneumonitis and cause of death was attributed to disease progression by the treating investigator.

AstraZeneca and Daiichi Sankyo will also present updated results from the BEGONIA Phase Ib/II trial at ESMO (Free ESMO Whitepaper) showing Datroway in combination with Imfinzi (durvalumab) continued to demonstrate robust anti-tumour activity as 1st-line treatment for patients with metastatic TNBC across PD-L1 expression levels and specifically in those with high PD-L1-expressing tumours. These results will be presented on Monday, 20 October (abstract #555MO).

AstraZeneca and Daiichi Sankyo are evaluating Datroway across stages and treatment settings of TNBC in three additional Phase III trials. TROPION-Breast03 is evaluating Datroway with or without Imfinzi in patients with Stage I-III TNBC with residual invasive disease after neoadjuvant systemic therapy. TROPION-Breast04 is evaluating neoadjuvant Datroway plus Imfinzi in patients with Stage II-III triple-negative or hormone receptor (HR)-low, HER2-low or -negative breast cancer. TROPION-Breast05 is evaluating 1st-line Datroway with or without Imfinzi in patients with metastatic TNBC whose tumours express PD-L1.

Notes

Triple-negative breast cancer
TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.1,2 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.3-5 Metastatic TNBC is the most aggressive type of breast cancer and has one of the worst prognoses, with median OS of just 12 to 18 months and only about 14% of patients living five years following diagnosis.3,6,7

While some breast cancers may test positive for oestrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.3 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.3 For patients with metastatic disease with PD-L1 expressing tumours, the addition of immunotherapy to chemotherapy has improved outcomes in the 1st-line setting.8,9 However, for the approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy remains the 1st-line standard of care.10,11

TROP2 is a protein broadly expressed in several solid tumours including TNBC.12 TROP2 is associated with increased tumour progression and poor survival in patients with breast cancer.13,14

TROPION-Breast02
TROPION-Breast02 is a global, multicentre, randomised, open-label Phase III trial evaluating the efficacy and safety of Datroway versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumours did not express PD-L1 as well as patients with PD-L1 expressing tumours who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrolment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as stable brain metastases.

The dual primary endpoints of TROPION-Breast02 are PFS as assessed by BICR and OS. Key secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response, disease control rate, pharmacokinetics and safety.

TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For more information, visit ClinicalTrials.gov.

Datroway
Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the US only) is a TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Datroway is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datroway is approved in more than 35 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on results from the TROPION-Breast01 trial.

Datroway is available in the US under accelerated approval for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy based on results from the TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. Datroway is approved in Russia for the same population.

(Press release, AstraZeneca, OCT 19, 2025, View Source [SID1234656785])

On October 19, 2025 Incyte (Nasdaq:INCY) reported the first clinical data evaluating its TGFβR2×PD-1 bispecific antibody (INCA33890) for patients with microsatellite stable (MSS) colorectal cancer; and its potent, selective and orally bioavailable KRAS G12D inhibitor (INCB161734) for patients with KRAS G12D mutations, specifically pancreatic ductal adenocarcinoma (PDAC). The data were featured in two oral sessions (Investigational immunotherapy; Abstract #1522MO and Developmental therapeutics; Abstract #916O, respectively) at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025.

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"The proof-of-concept data highlight the potential of INCA33890 and INCB161734 to address significant medical needs in patients with advanced solid tumors, including MSS colorectal cancer and PDAC," said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. "These results, including the favorable safety profiles as monotherapies, support continued clinical development. We look forward to exploring the development of these two novel targeted therapies in combination with current standard of care as frontline treatments."

INCA33890 (TGFβR2×PD-1)​

In an October 17, 2025, mini oral session at ESMO (Free ESMO Whitepaper), data were presented from the monotherapy arm (Part 1) of the INCA33890 Phase 1 trial, which included patients with advanced or metastatic solid tumors – including MSS colorectal cancer, ovarian cancer (OC), squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), gastric/gastroesophageal junction cancer (GC/GEJ) and PDAC – who experienced disease progression after receiving available therapies or were intolerant to, ineligible for or declined standard treatments, including immune checkpoint inhibitors. These patients received doses of INCA33890 ranging from 100 mg to 1,500 mg every two weeks (Q2W) to 900 mg intravenously (IV) every four weeks (Q4W) in continuous 28-day cycles. INCA33890 300 mg, 600 mg and 900 mg Q2W were selected as the recommended doses for expansion (RDE).

Initial data (cut-off July 25, 2025) showed promising clinical efficacy with INCA33890 treatment. This trial is ongoing, and the data will continue to mature. Of note:

INCA33890 demonstrated a manageable safety profile across all enrolled patients (n=260) – the occurrence and severity of immune related adverse reactions was similar to approved immune checkpoint inhibitors. The most common treatment-related adverse events (TRAEs) among individuals treated with INCA33890 across RDE (n=239) were fatigue (13.8%), pruritus (8.8%) and infusion-related reactions (8.4%).
Among patients with metastatic MSS colorectal cancer treated with INCA33890 at RDE (n=105), the vast majority (93.3%) had received more than two prior treatment regimens and 71.4% had active liver metastases at the time of treatment.
Within this cohort, 16 patients treated with INCA33890 responded (14 confirmed), with 15.2% achieving an objective response rate (ORR) and a median duration of therapy of 7.3 months.
The ORR among metastatic MSS colorectal cancer patients treated with INCA33890 was similar across RDE. Deep tumor responses were observed among patients with liver metastasis (n=9) – 12.0% achieved an ORR with a disease control rate (DCR) of 20.0%. Additionally, seven patients with no liver metastases treated with INCA33890 responded, achieving an ORR of 23.3% and DCR of 50.0%.
"Increased TGFβR2 expression is associated with poor prognosis in multiple solid tumor types, including colorectal cancer, which is third most common cancer and the second leading cause of cancer-related mortality worldwide," said Elena Garralda, M.D., Ph. D., Trial Investigator and Director of Early Drug Development at the Vall d’Hebron Institute of Oncology. "The efficacy data presented at ESMO (Free ESMO Whitepaper) in MSS colorectal cancer, coupled with tolerable safety profile, provide proof of concept for this differentiated approach of on-target inhibition of the TGF-β pathway. I look forward to seeing further development of this promising drug."

Evaluation of INCA33890 900 mg Q2W in combination with standard of care (SoC) treatments in patients with MSS colorectal cancer is ongoing. Dose escalation has been completed across combination therapy cohorts and no DLTs were identified. Incyte plans to initiate a registrational program for INCA33890 in MSS colorectal cancer in 2026.

INCB161734 (KRAS G12D)​

In an October 19, 2025, proffered paper session, data were presented from the monotherapy arm (Part 1) of the INCB161734 Phase 1 trial in patients with select advanced or metastatic solid tumors and documented KRAS G12D mutation – including PDAC, colorectal cancer, NSCLC, OC and other solid tumors – who received varying doses of INCB161734 ranging from 200 mg to 1,600 mg daily. The dose escalation portion of the study is complete – two doses, 600 mg daily and 1,200 mg daily, were selected for expansion.

Preliminary data (cut-off August 1, 2025) demonstrated evidence of clinical benefit in advanced or metastatic PDAC patients treated with INCB161734 (n=83). This trial is ongoing, and the data will continue to mature. Specifically:

INCB161734 demonstrated a manageable safety profile across all treated patients (n=136). No DLTs were reported in dose escalation, and the maximum tolerated dose (MTD) was not reached. No fatal adverse events (AEs) were considered related to treatment. The most common TRAEs across tumor types, nausea (58.1%), diarrhea (50.7%), vomiting (45.6%) and fatigue (17.4%), were mostly Grade 1.
PDAC patients receiving 600 mg (n=25) and 1,200 mg (n=29) INCB161734 daily demonstrated objective response rates (ORR; 20% and 34%) and high DCRs (64% and 86%). The study is ongoing for the majority of patients; data on durability of response is expected in the first half of 2026.
"PDAC is a highly aggressive cancer, and patients with G12D-mutated PDAC currently have an average five-year survival rate of less than ten percent," said Dr. Jayesh Desai, Tiral Investigator, Medical Oncologist and Associate Director of Clinical Research at the Peter MacCallum Cancer Centre. "It is encouraging to see promising antitumor activity and strong molecular response with INCB161734 monotherapy in this heavily pretreated patient population, and I believe these data speak to the potential of INCB161734 to be an impactful, selective targeted therapy for PDAC."

Evaluation of the data for INCB161734 in patients with PDAC is ongoing with results expected in 2026. Based on the findings, the company will conduct a comprehensive review of the data to inform next steps for the program, including discussions with regulatory authorities.

More information regarding the 2025 ESMO (Free ESMO Whitepaper) Congress and the data from Incyte’s oncology portfolio being featured at the meeting can be found on the ESMO (Free ESMO Whitepaper) website: View Source

Analyst Event and Webcast
The data from the ESMO (Free ESMO Whitepaper) oral presentations and additional results from INCA33890 in patients with MSS colorectal cancer and INCB161734 in patients with PDAC will also be discussed at an in-person analyst and investor event on Sunday, October 19, 2025, from 1:30 – 3:00 p.m. ET (7:30 – 9:00 p.m. CEST) at ESMO (Free ESMO Whitepaper).

The event will be webcasted and can be accessed via the Events and Presentations tab of the Investor section of Incyte.com and it will be available for replay for 30 days.

More information regarding the 2025 ESMO (Free ESMO Whitepaper) Congress can be found at: View Source

About INCA33890
INCA33890 is an investigational, TGFβR2×PD-1 bispecific antibody, developed in collaboration with Merus using their Biclonics antibody platform, engineered to block TGF-β–mediated signaling in T cells co-expressing TGF-β and PD-1. TGFβ is known to promote cancer immune evasion and predicts poor response to PD-(L)1 targeted therapies. INCA33890 aims to spare tissues where TGF-β signaling is important for normal function, avoiding the known toxicity of a broad blocking of the TGF-β pathway. INCA33890 offers a promising targeted treatment strategy for patients with advanced or metastatic solid tumors, including microsatellite stable colorectal cancer.1,2,3,4

The open-label, multicenter Phase 1 study (NCT05836324) is evaluating the safety, tolerability, dose-limiting toxicities (DLTs), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of INCA33890 when administered as a monotherapy and in combination with other standard-of-care treatments (i.e., bevacizumab, bevacizumab and FOLFIRI, bevacizumab and FOLFOX, and cetuximab) in adults (≥18 years old) with advanced or metastatic solid tumors.

The study includes Part 1 evaluating INCA33890 as a monotherapy with Part 1A (dose escalation) and Part 1B (dose expansion). Inclusion criteria for Part 1 requires patients to have experienced disease progression after receiving available therapies or that they were intolerant to, ineligible for or declined standard treatment. Part 2 will evaluate INCA33890 administered in combination with other protocol-defined treatment(s) based on cohort assignment and also includes dose escalation (Part 2A) and dose expansion (Part 2B).

Primary endpoints include evaluating DLTs up to 28 days and safety/tolerability. Key secondary endpoints focus on preliminary efficacy (i.e., objective response rate [ORR], disease control rate [DCR], duration of response [DOR]) up to two years and PK parameters.

For more information about the study, please visit: View Source

About INCB161734
INCB161734 is an investigational novel, selective and orally bioavailable small molecule inhibitor targeting G12D-mutated KRAS. KRAS is one of the most frequently altered driver oncogenes in solid tumors. The G12D mutation, which represents approximately 40% of oncogenic KRAS mutations in patients with PDAC, is associated with aggressive tumor phenotypes and poor clinical outcomes.

The open-label, dose-escalation and dose-expansion Phase 1 study (NCT06179160) is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of INCB161734 when administered as monotherapy and in combination with other anticancer therapies in patients with advanced or metastatic solid tumors harboring the KRAS G12D mutation. The study includes Part 1 evaluating INCB161734 as a monotherapy, with Part 1A (dose escalation), Part 1B (cohort dose expansion), Part 1C (pharmacodynamics) and Part 1D (food-effect). Part 2 will evaluate INCA161734 administered in combination with other protocol-defined treatment(s) based on cohort assignment and also includes dose escalation (Part 2A) and dose expansion (Part 2B).

Primary endpoints include DLTs and TEAEs. Key secondary endpoints include objective ORR, DCR, DOR and PK parameters.

For more information about the study, please visit: View Source

(Press release, Incyte, OCT 19, 2025, View Source [SID1234656801])

On October 19, 2025 The European Organisation for Research and Treatment of Cancer (EORTC) reported that the EORTC 1333/PEACE-3 trial has reached its final overall survival (OS) endpoint at the time of the final database lock on September 19, 2025.

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The EORTC 1333/PEACE-3 study is a randomized, open-label, multicentre phase III trial conducted in collaboration with Clinical Trial Ireland (CTI), the Canadian Urological Oncology Group (CUOG), the Latin American Cooperative Oncology Group (LACOG), and the French group GETUG/UNICANCER. A total of 446 asymptomatic or mildly symptomatic patients (Brief Pain Inventory score < 4) with metastatic castration-resistant prostate cancer (mCRPC) and ≥2 bone metastases were randomized 1:1 to receive either enzalutamide (160 mg daily) alone or enzalutamide plus six intravenous injections of radium-223 (55 kBq/kg every four weeks).

In the primary analysis, published in Annals of Oncology, the addition of six cycles of radium-223 to enzalutamide significantly improved the primary endpoint radiological progression-free survival (rPFS) from 16.4 months (95% CI 13.8–19.2) to 19.4 months (95% CI 17.1–25.3) (hazard ratio [HR] 0.69; 95% CI 0.54–0.87; p = 0.0009)¹, and an interim analysis at 80% of events that suggested an OS advantage for combining enzalutamide and Ra223.

The final overall survival analysis now confirms that the addition of six cycles of radium-223 to enzalutamide significantly prolongs overall survival, thereby reinforcing the findings of the interim analysis reported at the time of the primary publication.

Comprehensive results will be presented soon.

This trial is supported by an investigator driven clinical trial agreement from Bayer HealthCare Pharmaceuticals Inc. and Astellas Pharma Europe.

(Press release, EORTC, OCT 19, 2025, View Source [SID1234656768])

On October 19, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK-pathway-driven cancers, reported positive, updated efficacy and safety data from partner GenFleet Therapeutics’ Phase 1/2 monotherapy study in China of GFH375, an oral KRAS G12D (ON/OFF) inhibitor (VS-7375 outside of China) for patients with KRAS G12D mutant advanced pancreatic ductal adenocarcinoma (PDAC). Among 59 heavily pre-treated patients with advanced disease, who received two or more prior lines of therapy, an overall response rate (ORR) of 41% was achieved at the monotherapy recommended Phase 2 dose (RP2D) of 600 mg daily (QD). The updated data were featured in a late-breaking abstract for oral presentation by GenFleet Therapeutics at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 on October 19, 2025, in Berlin, Germany.

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"Patients with advanced pancreatic cancer and a KRAS G12D mutation tend to have a worse prognosis compared to other KRAS mutations. We are pleased to see that the updated data presented by our partner, GenFleet Therapeutics, continues to demonstrate encouraging clinical responses at the recommended Phase 2 dose, in a heavily pre-treated, often difficult to treat, patient population," said Dan Paterson, president and chief executive officer of Verastem Oncology. "These data add to the growing body of evidence supporting the therapeutic potential of KRAS G12D inhibition and importantly provide valuable insights as we continue to advance through our Phase 1/2a trial with VS-7375."

ESMO 2025 Presentation Highlights

GenFleet reported that 66 patients with advanced KRAS G12D mutant PDAC were treated with 600 mg QD of GFH375 monotherapy. In the study, 95.5% of patients were diagnosed with stage IV disease at study entry, and 68.2% of patients had received at least two prior lines of anticancer therapies, with 92.4% of patients receiving gemcitabine-based regimens and more than 50% receiving fluorouracil or irinotecan-containing regimens. As of the data cutoff of September 27, 2025, 59 efficacy-evaluable patients had at least one post-treatment tumor assessment and achieved an ORR of 40.7% (24/59) (confirmed and unconfirmed) and a disease control rate (DCR) of 96.7% (57/59) with the majority of patients (91.5%) experiencing a reduction in target lesions. Overall survival (OS) observed at month four was 92.2%. The median OS was not reached as of the data cutoff, with a median follow-up time of 5.65 months. The median progression-free survival (PFS) was 5.52 months with a median follow-up time of 5.65 months and a 4-month PFS rate of 78.2%. At evaluation, 31 (47%) of patients were still on treatment with the longest duration of treatment eclipsing one year (367 days).

The safety profile in PDAC patients was consistent with the previously reported data at recent medical congresses. As of the data cutoff date of August 27, 2025, the most frequent treatment-related adverse events (TRAEs) occurring in ≥20% of patients included diarrhea, neutrophil count decreased, vomiting, nausea, anemia, white blood cell count decreased, decreased appetite, hypoalbuminemia, platelet count decreased, asthenia, aspartate aminotransferase increased, and alanine transferase increased. Grade 3 TRAEs occurred in 20 patients (30.3%) and a Grade 4 TRAE (neutropenia) occurred in one patient (1.5%). Of the 66 patients in the safety population, four patients (6.1%) had a dose reduction and two patients (3%) discontinued due to TRAEs. No TRAE-related deaths were reported. The mean relative dose intensity was 93%.

About KRAS G12D

KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%), and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) specifically targeting KRAS G12D mutations in cancer.

About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor

VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared and initiated a Phase 1/2a clinical trial in June 2025. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024.

About the Phase 1/2a Study of VS-7375

The Phase 1/2a study will be conducted in the U.S., with the potential to expand globally, and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The starting dose for the Phase 1 study of 400 mg is based on the dose identified in the initial data from the GenFleet study to accelerate the trial’s progress. Verastem plans to dose escalate across levels where responses were observed in GenFleet’s study and will assess in the Phase 2a portion the efficacy and safety of VS-7375, both as monotherapy and in combination, in patients with advanced solid tumors, such as pancreatic, colorectal, and non-small cell lung cancers.

(Press release, Verastem, OCT 19, 2025, View Source [SID1234656786])