On October 17, 2025 Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President and COO: Toichi Takino; "Ono"), reported the two-year efficacy and safety results from its MOTION Phase 3 study of vimseltinib in patients with TGCT in cases where surgical removal of the tumor is not an option will be presented as a poster during the 2025 European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper), taking place October 17-21 in Berlin, Germany.

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"These long-term Phase 3 MOTION results add to the established body of evidence supporting vimseltinib as a best-in-class treatment for TGCT," said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. "TGCT often causes debilitating pain, stiffness and impaired mobility and these results demonstrate the durable benefit that vimseltinib can offer patients."

Summary of Data and Findings from the 2-year results of the MOTION Phase 3 Study

Methods

The global Phase 3 MOTION study (NCT05059262) aims to evaluate the efficacy and safety of vimseltinib for the treatment of TGCT in cases where surgical removal of the tumor is not an option.

The study consists of two parts. In Part 1, eligible study participants were assigned to receive either vimseltinib or matching placebo for 24 weeks. Participants assigned to placebo in Part 1 had the option to receive vimseltinib for Part 2. Part 2 was a long-term treatment phase in which all participants received open-label vimseltinib. Patients received vimseltinib 30 mg twice weekly in all periods. Objective response rate (ORR) based on best overall response was assessed by independent radiological review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and per Tumor Volume Score (TVS). Duration of response (DOR) and safety were also evaluated.

Efficacy

In these two-year results from the MOTION Phase 3 trial, vimseltinib continued to demonstrate robust and durable antitumor efficacy with a manageable safety profile that was consistent with prior reports. These long-term results support vimseltinib as a treatment option for patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability, where it is approved. These results are reported with two years of follow-up in patients randomized to vimseltinib in Part 1 and crossed over from placebo to vimseltinib in Part 2. The data cutoff for this analysis was February 22, 2025.

In total, 118 patients received vimseltinib. At data cutoff, 51% (60/118) remained on treatment. With at least 2 years of follow-up, results demonstrate robust and durable antitumor activity with vimseltinib per RECIST v1.1 and per TVS, including in patients who crossed over to vimseltinib in Part 2.

Of 83 patients randomized to vimseltinib in Part 1, 73 continued open-label treatment in Part 2. Median (range) treatment duration was 23.6 months (2 to 36).
Of the 40 patients randomized to placebo in Part 1, 35 crossed over to vimseltinib in Part 2. Median treatment duration for this group was 19.1 months (1 to 30).
ORR on study per RECIST v1.1 was 48% (40/83) for patients randomized to vimseltinib and 54% (19/35) for those who crossed over to vimseltinib. ORR on study per TVS was 81% (67/83) for patients randomized to vimseltinib and 71% (25/35) for those who crossed over to vimseltinib.
The corresponding median DOR per RECIST v1.1 and per TVS was still not reached.
Safety

Vimseltinib continued to have a manageable safety profile that was consistent with prior reports with no new safety signals.

Most treatment-emergent adverse events (TEAEs) were grade 1/2, and grade 3/4 TEAEs were similar between randomized vimseltinib and crossover groups.
There were no new TEAEs in ≥15% of patients receiving vimseltinib and no new serious adverse events in more than one patient.
Serum enzyme elevations were consistent with the known mechanism of action of CSF1R inhibition, and there was no evidence of cholestatic hepatotoxicity or drug-induced liver injury.
About Vimseltinib

Vimseltinib is an oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. Vimseltinib has been developed using Deciphera’s proprietary switch-control kinase inhibitor platform. It has been approved in the United States for adult patients with symptomatic TGCT for which surgical resection will potentially cause worsening functional limitation or severe morbidity, and in the European Union for adult patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability.

About Tenosynovial Giant Cell Tumor (TGCT)

TGCT is caused by a dysregulation in colony-stimulating factor 1 (CSF1) gene leading to overproduction of CSF1 and recruitment of colony-stimulating factor 1 receptor (CSF1R)-positive inflammatory cells into the lesion.1 TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS). TGCT is a rare, locally aggressive neoplasm that can grow and cause damage to surrounding tissues and structures inducing pain, swelling, and limitation of movement of the joint. Surgery is the main treatment option; however, these tumors tend to recur, particularly in diffuse-type TGCT. If untreated or if the tumor continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability. For a subset of patients, surgical resection will potentially cause worsening functional limitation or severe morbidity. Systemic treatment options are limited and new therapeutic options are needed.

(Press release, Ono, OCT 17, 2025, View Source [SID1234656755])

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

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

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

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

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

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

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

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

Key Findings from OptimUM-09

•
Tumor shrinkage and eye preservation

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

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

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

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

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

•
Predicted radiation reduction and visual preservation

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

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

•
Improved visual acuity during neoadjuvant treatment

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

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

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

•
Safety and Tolerability:

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

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

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

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

On October 17, 2025 TOLREMO therapeutics AG (TOLREMO) reported encouraging clinical data from 34 patients with advanced solid tumors treated with TT125-802 in the dose escalation part of an ongoing first-in-human study (NCT06403436). The data will be presented on October 19 at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany, and highlights TT125-802’s confirmed clinical activity and favorable safety profile.

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TT125-802 is an orally available small-molecule inhibitor that selectively blocks the bromodomains of CBP/p300, transcriptional co-activators implicated in non-oncogene addiction – a key driver of cancer and drug resistance that functions in parallel to oncogenic pathways. This update expands on initial data presented at ASCO (Free ASCO Whitepaper) earlier this year, establishing TT125-802 as the first CBP/p300 bromodomain inhibitor to report clinical activity across a variety of solid tumors, including durable confirmed responses in non-small cell lung cancer (NSCLC).

In the now completed dose escalation part of the study, 34 heavily pre-treated solid tumor patients received TT125-802 across 5 dose escalation cohorts (15 mg QD – 60 mg BID) and 2 cohorts examining the role of food on exposures. No MTD was reached and TT125-802 was safe and well tolerated. The most common drug-related AEs were dysgeusia and hyperglycemia. No thrombocytopenia was observed. The recommended dose was selected at 60 mg once a day on a continuous basis, without food restriction.

Suppression of CBP/p300 target pathways was confirmed in patient hair follicles by RNA-seq.

Anti-tumor activity was observed across all dose levels in this heavily pre-treated population. 4 patients stayed on study for over one year, including 3 patients with adenoid cystic carcinoma and one patient with a bulky dedifferentiated liposarcoma. 3 patients (EGFR exon 19 delta, KRAS-G12C, squamous NSCLC) achieved a deep confirmed partial response (PR). The EGFRmut and KRAS-G12Cmut patients had progressed on an EGFR inhibitor and KRAS-G12C inhibitor, respectively, in a prior line of therapy. Both had a rapid PR after 6 weeks of TT125-802 monotherapy and remained progression-free for almost 7 months. The squamous NSCLC patient had progressed on standard-of-care therapy and had a PR after 12 weeks of TT125-802. The patient was on study for 5.5 months until progression.

Dr. Omar Saavedra Santa Gadea at NEXT Oncology Hospital Quirónsalud in Barcelona, an investigator on the study said, "It is remarkable to see such rapid, deep and durable responses in NSCLC patients who had exhausted all prior treatments. TT125-802’s mechanism targeting non-oncogene addiction offers a novel approach to improving clinical outcomes for patients in this high-need setting."

"These results validate our approach to target epigenetic mechanisms driving cancer and drug resistance and support the continued clinical development of TT125-802 in patients with solid tumors and hematological malignancies," said Florian Vogl, CMO at TOLREMO. "The absence of thrombocytopenia, a common toxicity with bromodomain inhibitors, sets TT125-802 apart. The wide therapeutic window opens up clinical opportunities for TT125-802 which have so far been unattainable for this class of drugs."

"We will now initiate a combination study investigating the efficacy of TT125-802 in combination with an EGFR inhibitor and a KRAS-G12C inhibitor in the respective oncogene-driven NSCLC populations, and with docetaxel in squamous NSCLC patients. We look forward to demonstrating the full therapeutic potential of TT125-802 for patients in need," said Stefanie Flückiger-Mangual, Ph.D., CEO and co-founder of TOLREMO.

Details of the poster presentations are:

Abstract Title: Clinical activity of TT125-802, a highly selective bromodomain inhibitor of CBP/p300, in advanced solid tumors: update on the ongoing phase I study

Authors: O. Saavedra, E. Garralda, V. Boni, J. Fuentes Antrás, I. Colombo, M. Imbimbo, G. Molina, I. Braña, K. Homicsko, F.D. Vogl, D. Gruber, S. Costanzo, A. Cesano, S. Flückiger-Mangual

Category: Developmental Therapeutics

Presentation Number: 978P

Date/Time: 19 October 2025 / 12:00 – 12:45 CEST

TOLREMO is assessing TT125-802 in a first-in-human, multicenter Phase 1 trial (NCT06403436) to evaluate the safety, tolerability, pharmacokinetics, and efficacy in patients with advanced solid tumors. The company recently received two U.S. FDA Fast Track designations for the treatment of patients with advanced or metastatic EGFR-mutant or KRAS-G12C-mutant NSCLC with disease progression on at least one prior line of therapy.

(Press release, TOLREMO, OCT 17, 2025, View Source [SID1234656739])

On October 17, 2025 Astrazeneca reported positive results from the MATTERHORN Phase III trial showed perioperative treatment with Imfinzi (durvalumab) in combination with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of overall survival (OS) versus chemotherapy alone. Patients were treated with neoadjuvant Imfinzi in combination with chemotherapy before surgery, followed by adjuvant Imfinzi in combination with chemotherapy, then Imfinzi monotherapy. The trial evaluated this regimen versus perioperative chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers.

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These results will be presented today in a Proffered Paper session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany (abstract #LBA81).

In the final OS analysis, results showed the Imfinzi and FLOT perioperative regimen reduced the risk of death by 22% compared with chemotherapy alone (based on a hazard ratio [HR] of 0.78; 95% confidence interval [CI] 0.63-0.96; p=0.021). Median OS was not yet reached for either arm. An estimated 69% of patients treated with the Imfinzi-based regimen were alive at three years compared with 62% in the FLOT-only arm.

Josep Tabernero, MD, PhD, head of the Medical Oncology Department at the Vall d’Hebron University Hospital and director of the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain, and principal investigator in the trial, said: "The MATTERHORN data are transformative for patients with early gastric and gastroesophageal cancers, where recurrence is common and long-term prognosis remains poor despite curative-intent surgery and chemotherapy. Nearly seven in 10 patients treated with the durvalumab-based perioperative regimen were alive at three years, and the survival benefit was observed regardless of PD-L1 status. With results like these, this novel treatment should become the new standard of care in this curative-intent setting."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "Imfinzi’s overall survival results, which demonstrate a 22 per cent reduction in the risk of death, could change the treatment paradigm for patients with early gastric and gastroesophageal cancers. This is the first immunotherapy-based perioperative regimen to significantly extend survival in this setting, and these results illustrate our strategy to move novel treatments into early-stage cancers where cure is possible."

Summary of OS results: MATTERHORN

Imfinzi-based regimen

(n=474)

Chemotherapy regimen

(n=474)

OS i,ii

mOS (in months)iii

NR (NR-NR)

NR (NR-NR)

HR (95% CI) iv

0.78 (0.63-0.96)

Stratified log-rank p-value

0.021

Number of deaths, n (%)

160 (33.8)

192 (40.5)

Data maturity

37.1%

OS rate at 18 months, %iii

81.1

77.1

OS rate at 24 months, %iii

75.5

70.4

OS rate at 36 months, %iii

68.6

61.9

OS, PD-L1 TAP ≥1% (n)v

426

427

Number of deaths, n (%)

143 (33.6%)

172 (40.3%)

mOS (in months)

NR (NR-NR)

NR (NR-NR)

HR (95% CI)

0.79 (0.63-0.99)

OS, PD-L1 TAP <1% (n)v

48

47

Number of deaths, n (%)

17 (35.4%)

20 (42.6%)

mOS (in months)

NR (43.66-NR)

NR (21.72-NR)

HR (95% CI)

0.79 (0.41-1.50)

i. OS data cut-off date was 1 September 2025
ii. Median follow-up duration for OS in all subjects at data cut-off: 39.6 months for Imfinzi plus FLOT and 38.6 months for placebo plus FLOT
iii. Calculated by Kaplan–Meier method
iv. The analysis was performed using a stratified Cox proportional hazards model, adjusting for geographic region, clinical lymph node status and PD-L1 expression status
v. TAP, Tumour area positivity

Significance threshold p <0.0499
NR, not yet reached

Results from an additional analysis of the association between pathologic outcomes and event-free survival (EFS) in MATTERHORN demonstrated that any degree of pathologic response was associated with improved EFS in the Imfinzi arm versus the comparator arm (pathologic complete response [pCR] HR 0.29; 95% CI, 0.08-0.96; major pathologic response [MPR] HR 0.32; 95% CI, 0.15-0.68); any pathologic response: HR 0.60; 95% CI, 0.46-0.79). Additionally, EFS was improved regardless of pathologic lymph node status at the time of surgery (no nodal involvement: HR 0.74; 95% CI, 0.46-1.18; nodal involvement: HR 0.77; 95% CI, 0.58-1.02).

In a previously reported interim analysis for the key primary endpoint of EFS, patients treated with the Imfinzi-based perioperative regimen showed a 29% reduction in the risk of disease progression, recurrence or death versus chemotherapy alone (based on an EFS hazard ratio [HR] of 0.71; 95% confidence interval [CI] 0.58-0.86; p<0.001). The safety profile for Imfinzi and FLOT chemotherapy was consistent with the known profiles of each medicine, and the percentage of patients that completed surgery was similar compared to chemotherapy alone. Grade 3 or higher adverse events due to any cause were similar between the two arms.

Notes
Gastric and gastroesophageal junction cancers

Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-highest leading cause of cancer mortality.1 Nearly one million new patients were diagnosed with gastric cancer in 2022, with approximately 660,000 deaths reported globally.1 In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies.2 In 2024, there were approximately 43,000 drug-treated patients in the US, European Union (EU), and Japan with early-stage and locally advanced gastric or GEJ cancer.3 Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030.4

GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach.5

Disease recurrence is common in patients with resectable gastric cancer despite undergoing surgery with curative intent and treatment with neoadjuvant/adjuvant chemotherapy.6 Approximately one in four patients with gastric cancer who undergo surgery develop recurrent disease within one year, and the five-year survival rate remains poor, with less than half of patients alive at five years.6-7

MATTERHORN
MATTERHORN is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 948 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery. This was followed by Imfinzi or placebo every four weeks for up to 12 cycles after surgery (including two cycles of Imfinzi or placebo plus FLOT chemotherapy and 10 additional cycles of Imfinzi or placebo monotherapy).

In the MATTERHORN trial, the primary endpoint is EFS, defined as time from randomisation until the date of one of the following events (whichever occurred first): RECIST (version 1.1, per blinded independent central review assessment) progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period; RECIST progression/recurrence during the adjuvant period; non-RECIST progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period or discovered during surgery; progression/recurrence confirmed by biopsy post-surgery; or death due to any cause. Key secondary endpoints include pathologic complete response rate, defined as the proportion of patients who have no detectable cancer cells in resected tumour tissue following neoadjuvant therapy, and OS. The trial enrolled participants in 176 centres in 20 countries, including in the US, Canada, Europe, South America and Asia.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In GI cancer, Imfinzi is approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer (BTC) and in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

In addition to its indications in GI cancers, Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC.

Perioperative Imfinzi in combination with neoadjuvant chemotherapy is approved in the US, EU, Japan and other countries for patients with muscle-invasive bladder cancer based on results from the NIAGARA Phase III trial. Additionally, in May 2025, Imfinzi added to Bacillus Calmette-Guérin induction and maintenance therapy met the primary endpoint of disease-free survival for patients with high-risk non-muscle-invasive bladder cancer in the POTOMAC Phase III trial.

Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in the US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in the EU and Japan.

Since the first approval in May 2017, more than 414,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several GI cancers.

(Press release, AstraZeneca, OCT 17, 2025, View Source [SID1234656741])

On October 17, 2025 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, reported new data from its botensilimab (BOT), a multifunctional, Fc-enhanced CTLA-4 antibody and balstilimab (BAL), a PD-1 inhibitor, combination demonstrating durable survival across multiple cancer types in late-stage patients who have limited treatment options. The results, featured in an oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany presented by Dr. Michael Gordon of HonorHealth Research Institute, include emerging two-year survival plateaus indicating a strong clinical signal that BOT/BAL’s benefit may be agnostic to tumor type.

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"With longer follow up, we’re finding that approximately 40% of patients with very limited survival expectation are alive at two years," said Michael S. Gordon, MD, HonorHealth Research Institute. "These results are in patients with cancers that historically have been resistant to earlier immunotherapy approaches or have progressed following prior immunotherapy treatment, and they support advancing randomized trials like the phase 3 BATTMAN trial to create an immunotherapy option for patients who have historically had none."

Highlights from the Oral Presentation (Abstract #1517MO):

New data from expansion cohorts of 411 patients (339 evaluable for efficacy) enrolled in the Phase 1b C-800-01 study evaluating BOT/BAL in patients with advanced, refractory disease across more than 5 cancer types.

61% of patients enrolled received three or more prior lines of therapy
Objective response rates (ORR): 17% across both BOT 1 mg/kg and 2 mg/kg doses
Signals of benefit across tumor types, including those historically unresponsive to immunotherapy, had prior treatment with checkpoint inhibitors, and/or with active liver metastases.
2-year median overall survival (OS): 39%
Median OS (mOS): 17.2 months
Combination was well tolerated with most immune‑related side effects were reversible and gastrointestinal in nature; no treatment‑related deaths occurred
Immune activation correlated with improved survival
These findings build on previously reported 2-year overall survival of 42% and median OS of 20.9 months with BOT/BAL in refractory MSS mCRC with non-liver metastasesi and complement emerging data in the neoadjuvant setting, where BOT/BAL has also shown activity across multiple tumor typesii, further underscoring the platform potential of Agenus’ next-generation Fc-enhanced CTLA-4.

In a further validation of its clinical impact, the French National Authority for Health (HAS) recently authorized BOT in combination with BAL under France’s Compassionate Access (AAC) early access program. This marks the first government-funded access pathway in France, for patients with refractory microsatellite‑stable (MSS) metastatic colorectal cancer (mCRC) who have exhausted all available treatment options.

"BOT/BAL’s immune activation profile is truly differentiated," said Steven J. O’Day, MD, Chief Medical Officer, Agenus. "We are seeing consistent signals that this combination can convert ‘cold,’ IO‑resistant tumors into responsive ones, not only in late-line settings but potentially in earlier lines where immunotherapy may deliver even greater benefit."

Broader Presence at ESMO (Free ESMO Whitepaper) 2025

In addition to the pan-tumor dataset, three additional posters will be presented highlighting clinical activity across hard-to-treat cancers:

Cervical cancer: Results from the global Phase 2 RaPiDs trial (Abstract #2952)
MSS mCRC: A Phase 1 trial of BOT/BAL + regorafenib (Abstract #6197)
Non-melanoma skin cancer: Data from the AGENONMELA study (Abstract #7273)
These presentations further support the breadth and versatility of Agenus’ immunotherapy pipeline across diverse cancer types and clinical settings.

(Press release, Agenus, OCT 17, 2025, View Source [SID1234656742])