On October 19, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported results from the Phase III HARMONi-6 trial, conducted in China and sponsored by our partner, Akeso, Inc. (HKEX Code: 9926.HK), featuring the novel, potential first-in-class investigational bispecific antibody, ivonescimab. The data was presented today as part of the Presidential Symposium at the European Society for Medical Oncology 2025 Congress (ESMO 2025) in Berlin, Germany.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The HARMONi-6 presentation, Phase III Study of Ivonescimab plus chemotherapy versus Tislelizumab plus chemotherapy as First-line Treatment for advanced squamous non-small cell lung cancer (HARMONi-6), evaluated ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, a PD-1 inhibitor, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) irrespective of PD-L1 expression. HARMONi-6 is a single region, multi-center, Phase III study conducted in China sponsored by Akeso with all relevant data exclusively generated, managed, and analyzed by Akeso.

The trial results were presented by Dr. Shun Lu, MD, PhD, Chief of Shanghai Lung Cancer Center at Shanghai Chest Hospital, Professor of Medicine at Shanghai Jiaotong University, and associate editor for the Journal of Thoracic Oncology.

In major markets globally, first-line therapy for patients with advanced non-small cell lung cancer without driver mutations is most commonly a PD-1 inhibitor plus platinum-based chemotherapy. Prior to HARMONi-6, there were no known Phase III clinical trials in advanced NSCLC which have shown a statistically significant and clinically meaningful improvement compared to PD-(L)1 inhibitor therapy in combination with chemotherapy in a head-to-head setting.

Clinically Meaningful Efficacy

In the HARMONi-6 planned interim analysis of progression-free survival (PFS), ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint, PFS, by Independent Radiologic Review Committee (IRRC), when compared to tislelizumab in combination with chemotherapy, achieving a hazard ratio (HR) of 0.60 (95% CI: 0.46, 0.78; p<0.0001). A clinically meaningful benefit was demonstrated across clinical subgroups, including those with either PD-L1 negative or positive expression. Both the overall response rate (ORR) measured according to RECIST v1.1 criteria, as well as the duration of response (DoR) were higher in patients treated with ivonescimab plus chemotherapy compared to those treated with tislelizumab plus chemotherapy.

HARMONi-6 ITT (n=532):

Ivonescimab + Chemo

Tislelizumab + Chemo

Median Follow-up: 10.28 mos

(n=266)

(n=266)

Median PFS

11.14 mos

(95% CI: 9.86, NE)

6.90 mos

(95% CI: 5.82, 8.57)

PFS Stratified HR

0.60

(95% CI: 0.46, 0.78; p<0.0001)

ORR

75.9%

66.5%

DoR

11.20 mos

(95% CI: 8.54, NE)

8.38 mos

(95% CI: 5.72, NE)

ITT: Intention-to-Treat population; mos.: months; NE: not established

HARMONi-6 PD-L1 Subgroup Analyses

Ivonescimab + Chemo vs.

Tislelizumab + Chemo

PD-L1 Negative (PD-L1 TPS <1%) PFS stratified HR

0.55

Ivonescimab + Chemo n=105; Tislelizumab + Chemo n=105

(95% CI: 0.37, 0.82)

PD-L1 Positive (PD-L1 TPS >1%) PFS stratified HR

0.66

Ivonescimab + Chemo n=161; Tislelizumab + Chemo n=161

(95% CI: 0.46, 0.95)

Overall survival (OS) data was not yet mature at the time of the data cutoff and will be evaluated in the future.

Manageable Safety Profile

Ivonescimab demonstrated an acceptable and manageable safety profile in the HARMONi-6 study, which was consistent with previous Phase III studies conducted studying ivonescimab.

In squamous NSCLC, VEGF-A monoclonal antibodies have not been approved by health authorities including the FDA and have had limited clinical development based on historical early phase clinical trials, primarily due to significant risks of toxicity, including hemorrhage and other life-threatening, bleeding-related complications. The results of this study further validate the unique mechanism of action of ivonescimab, including key differences as compared to separately administering an anti-PD-1 monoclonal antibody and an anti-VEGF monoclonal antibody.

In this Phase III study, there were nine patients (3.4%) who discontinued ivonescimab plus chemotherapy due to treatment-related adverse events (TRAEs) compared to 11 patients (4.2%) who discontinued tislelizumab plus chemotherapy due to TRAEs. There were eight patients (3.0%) in the ivonescimab plus chemotherapy arm and 10 patients (3.8%) in the tislelizumab plus chemotherapy arm who died as a result of TRAEs in this Phase III study. The most frequent TRAEs for ivonescimab treatment in combination with chemotherapy were common chemotherapy-related AEs, including alopecia, anemia, and various laboratory abnormalities, including neutrophil, white blood cell, and platelet count decreases. Grade 3 or higher immune-related adverse events occurred in 9.0% of patients receiving ivonescimab in combination with chemotherapy and 10.2% of patients receiving tislelizumab in combination with chemotherapy. Grade 3 or higher adverse events that were possibly VEGF-related in the ivonescimab plus chemotherapy arm were 7.5% vs. 2.3% for tislelizumab plus chemotherapy. Most of the possibly VEGF-related adverse events occurring in the ivonescimab plus chemotherapy arm were classified as Grade 1 or 2. Of note, Grade 3 or higher hemorrhage events were observed in five patients in the ivonescimab plus chemotherapy arm compared to two patients in the tislelizumab plus chemotherapy arm in this study.

HARMONi-6

Ivonescimab + Chemo

(n=266)

Tislelizumab + Chemo

(n=265)

Serious TRAEs (TRSAEs)

32.3%

30.2%

TRAEs Leading to Drug Discontinuation

3.4%

4.2%

TRAEs Leading to Death

3.0%

3.8%

Grade 3+ Immune-related

9.0%

10.2%

Grade 3+ Possibly VEGF-related*

7.5%

2.3%

*In the ivonescimab plus chemotherapy arm, possibly VEGF-related Grade 3+ events were largely driven by conditions such as hypertension (3.0%) and proteinuria (2.3%) and largely did not lead to the discontinuation of ivonescimab. TRAE: treatment-related adverse event

"The novel mechanism of action of ivonescimab may allow for an improved clinical profile and longer duration of therapy, which help improve outcomes – this distinguishes ivonescimab from other PD-1 monoclonal antibodies and PD-(L)1 plus VEGF treatments administered separately," added Dr. Maky Zanganeh, Co-Chief Executive Officer and President of Summit. "No more striking is this result than in squamous NSCLC where the benefit of anti-VEGF therapy has been largely unrealized. Combined with the improved benefit in patients across all levels of PD-L1 expression, implying a true improvement in the immunotherapy activity, this study of ivonescimab in combination with chemotherapy provides rich context as to the potential benefit of ivonescimab across solid tumors, reaffirming its incredible potential to help a wide variety of patients suffering from cancer."

HARMONi-6 Clinical Trial Results Published in The Lancet

Today The Lancet published a manuscript titled, "Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial." The publication is based on the results of HARMONi-6, a single region, multi-center, Phase III study conducted in China sponsored by Akeso, with data generated and analyzed by Akeso.

"HARMONi-6 is yet another meaningful milestone for ivonescimab, Team Summit, and our partners at Akeso, and most importantly, continues to advance a potential treatment option for patients living with difficult-to-treat cancers," said Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit. "We remain extraordinarily proud of our partnership with Akeso and their ongoing clinical accomplishments and advancement of ivonescimab in solid tumors. We also would like to express our heartfelt appreciation to those physicians and patients in China who participated in this important study, who are helping to advance the treatment of patients around the world with this incredibly innovative therapy."

HARMONi-3 Clinical Trial Update

Summit is currently enrolling patients in the HARMONi-3 study. HARMONi-3 is a multiregional Phase III clinical trial sponsored by Summit which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab, an anti-PD-1 antibody, combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC. HARMONi-3 is currently enrolling patients globally and is conducted with registrational intent for the United States and other regions within Summit’s license territories. The dual primary endpoints for this study are PFS and OS.

Summit has amended the protocol for the HARMONi-3 study in order to separate the statistical analysis (i.e., the outcome) of the primary endpoints by histology. Therefore, there will be separate analyses conducted to evaluate ivonescimab plus chemotherapy compared to pembrolizumab plus chemotherapy in patients with squamous NSCLC and in patients with non-squamous NSCLC.

As a result of having two separate intention-to-treat analyses within the HARMONi-3 study, the analyses for squamous tumors and non-squamous tumors may be conducted at separate times, as each analysis will be conducted upon the prespecified numbers of events being reached in the separate cohorts.

Summit currently expects to complete enrollment in the squamous cohort of HARMONi-3 in the first half of 2026 and expects to reach the prespecified number of events for the PFS primary endpoint analysis for this cohort in the second half of 2026. An interim analysis for overall survival may be conducted at a similar time.

At present time, Summit expects to complete enrollment in the non-squamous cohort of HARMONi-3 in the second half of 2026 and expects to reach the prespecified number of events for the PFS primary endpoint analysis for this cohort in the first half of 2027. An interim analysis for overall survival is planned to be conducted based upon reaching a prespecified number of events.

In order to sufficiently power each of the dual primary endpoints in both cohorts of this study, Summit plans to enroll 600 patients with squamous NSCLC and 1,000 patients with non-squamous NSCLC.

Reference Comparison of Results of 1L Squamous NSCLC Studies Evaluating Pembrolizumab or Tislelizumab Plus Chemotherapy Compared to Chemotherapy

Study Data at

Initial Readout

Study Regions

Median PFS

(PD-1 +

Chemo Arm)

Hazard Ratio

vs. Chemo*

Median

Follow-up

Time

Source

KEYNOTE-407

(n=559)

Multiregional Study

6.4 months

HR=0.56

7.8 months

Paz-Ares, NEJM, 2018

RATIONALE-307

(n=360)

China Regional Study

7.6 months

HR=0.52*

8.6 months

Wang, JAMA Oncology, 2021

*RATIONALE-307 compared tislelizumab + carboplatin + paclitaxel (Arm A) vs. carboplatin + paclitaxel (Arm C) and separately tislelizumab + carboplatin + nab-paclitaxel (Arm B) vs. carboplatin + paclitaxel (Arm C). The study randomized patients 1:1:1 between the three arms. The median PFS results for tislelizumab + carboplatin + paclitaxel (Arm A) and tislelizumab + carboplatin + nab-paclitaxel (Arm B) were the same. The hazard ratios were 0.52 for Arm A vs. Arm C and 0.48 for Arm B vs. Arm C. KEYNOTE-407 randomized patients to receive either pembrolizumab or placebo plus carboplatin and either paclitaxel or nab-paclitaxel; the study was stratified by the choice of taxane.

Conference Call

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

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

About Ivonescimab

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

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

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

Summit began its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In early 2025, the Company began enrolling patients for HARMONi-7. Summit intends to open clinical trial sites in the United States for the Phase III HARMONi-GI3 study in colorectal cancer (CRC) by the end of 2025.

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

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

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

HARMONi-GI3 is a planned Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC. In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.

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

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

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

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

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

(Press release, Summit Therapeutics, OCT 19, 2025, View Source [SID1234656802])

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 Carsgen therapeutcis reported primary plasma cell leukemia (pPCL) is a rare and highly aggressive plasma cell malignancy, often associated with complex genetic abnormalities. There is currently no standard treatment regimens, and conventional therapies for multiple myeloma are typically used. While targeted agents and autologous hematopoietic stem cell transplantation can slightly extend the overall survival of pPCL patients to 1.5–3 years, relapsed/refractory pPCL after multiple lines of therapy presents a significant clinical challenge due to the extremely limited treatment options and rapid disease progression, making it difficult to re-induce remission with existing therapies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CT0596 is an allogeneic BCMA-targeted CAR-T therapy developed using CARsgen’s proprietary THANK-u Plus platform. It is currently being evaluated in investigator-initiated trials for plasma cell malignancy. As of the data cutoff date (Oct 17, 2025), two patients with relapsed/refractory pPCL had been enrolled. Details are as follows:

pPCL-01:

A 62-year-old male with IgG-λ type experienced poor disease control and rapid progression despite previous autologous hematopoietic stem cell transplantation and treatment with triple classes of drugs (proteasome inhibitor, immunomodulatory agent, and CD38 monoclonal antibody). By the screening period, his serum free light chain level had reached 10,374.86 mg/L. The patient underwent two CAR-T cell infusions approximately two months apart: he first received low-dose lymphodepletion and a relatively lower dose of CAR-T cells per protocol, then followed one cycle of bridge therapy. About one month after the failure of bridge therapy, he received a second CAR-T cell infusion. Following this infusion, he developed Grade 2 CRS, Grade 4 cytopenia, and a lung infection, but recovered after supportive treatment including tocilizumab, corticosteroids, autologous stem cell infusion, and anti-infective therapy. CAR-T cells expanded robustly, with a peak copy number (Cmax) of 161,971 copies/μg gDNA, and copy numbers remained at 10³ by Week 8. Efficacy assessments at both Week 4 and Week 8 post-infusion showed stringent complete response (sCR), and bone marrow minimal residual disease (MRD) was negative (< 10⁻⁶) at Week 4.

pPCL-02:

A 70-year-old male with κ light chain had previously been treated with triple classes of drugs (proteasome inhibitor, immunomodulatory agent, and CD38 monoclonal antibody). The patient developed Grade 1 CRS, Grade 4 neutropenia, and thrombocytopenia following lymphodepletion and CAR-T cell infusion. The CRS and cytopenias were resolved after treatment with tocilizumab and other supportive measures. CAR-T cells expanded robustly, with a Cmax of 151,654 copies/μg gDNA. The patient achieved sCR at the Week 4, Week 8, and Week 12 assessments post-infusion, with bone marrow MRD negative (< 10⁻⁶) at both Week 4 and Week 12.

Based on the current findings, CT0596 has exhibited robust and rapid efficacy in heavily pretreated patients with rapidly progressive relapsed/refractory pPCL. Both pPCL patients achieved sCR following CT0596 infusion, with peak CAR-T cell copy numbers exceeding 10⁵ copies/μg gDNA. Aside from expected CAR-T-associated toxicities such as CRS and hematologic adverse events, no significant organ toxicities were observed, indicating a manageable safety profile. These results lend strong support to the continued investigation of CT0596 across a broader spectrum of plasma cell neoplasms.

About CT0596

CT0596 is an allogeneic BCMA-targeted CAR-T therapy developed using CARsgen’s proprietary THANK-u Plus platform. It is currently being evaluated in investigator-initiated trials for relapsed/refractory multiple myeloma (R/R MM) or plasma cell leukemia (PCL). CT0596 demonstrated preliminary favorable tolerability and encouraging efficacy signals. Further investigation is planned in additional plasma cell malignancies and autoimmune diseases mediated by autoreactive plasma cells. The company anticipates submitting an Investigational New Drug (IND) application in the second half of 2025.

(Press release, Carsgen Therapeutics, OCT 19, 2025, View Source;preliminary-clinical-data-of-carsgens-allogeneic-bcma-car-t-product-ct0596-for-the-treatment-of-primary-plasma-cell-leukemia-302588331.html [SID1234656799])

On October 19, 2025 Multitude Therapeutics, Inc., a clinical stage biopharmaceutical company focused on the development of ADC drugs, reported interim results from its ongoing Phase I/II open-label, multicenter dose escalation and expansion study evaluating AMT-253, a MUC18-directed antibody-drug-conjugate (ADC), in patients with melanoma and other advanced solid tumors. The data are being presented on October 19th at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting being held in Berlin, Germany.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Phase I/II clinical trials are ongoing in both Australia and China. This first-in-human study will evaluate the Maximum Tolerated Dose (MTD) / the Recommended Phase II Dose (RP2D), safety, tolerability, anti-tumor activity, pharmacokinetics, pharmacodynamics and immunogenicity of AMT-253, in patients with advanced solid tumors. The Phase Ia portion will determine the recommended doses for expansion, and the Phase Ib/II portion will focus on further characterizing safety and efficacy in select tumor types.

As of September 8th, 2025, safety data are available for 170 patients who have received AMT-253 once every three weeks (Q3W) at doses ranging from 1.6 to 5.6 mg/kg. Primary tumor types are melanoma, endometrial cancer, cervical squamous cancer and uterine leiomyosarcoma. In heavily pretreated melanoma patients, with prior lines of therapy ranging from 1-7, promising efficacy was observed without MUC18 preselection. The overall response rate (ORR) was 28.6% in all melanomas (16/56, 15 confirmed, 1 unconfirmed still on-treatment) across all dose levels. In melanoma patients without prior chemotherapy, ORR was 35% (7/20, all confirmed), 50% (5/10; 4 confirmed, 1 unconfirmed still on-treatment), and 33.3% (1/3, confirmed) for the cutaneous, acral, and mucosal subtypes, respectively; preliminary mPFS was 8.6, 8.3, and 11.0 months. Among 18 cutaneous melanoma patients at the potential expansion doses, ORR was 38.9% (7/18, all confirmed), and preliminary mPFS was 8.6 months. Preliminary antitumor activity was also observed in endometrial cancer, cervical squamous carcinoma and uterine leiomyosarcoma patients. Responses were observed across MUC18 expression levels in all tumor patients evaluated. AMT-253 showed a safety profile consistent with other topoisomerase-1 (TOP1) inhibitor–based ADCs, with manageable hematologic toxicities as the most common treatment-related adverse events. No treatment-related cases of neuropathy or pneumonitis were observed as of the data cutoff.

"We are excited by the durable antitumor activity observed in the early clinical results of AMT-253, particularly in unselected, late-line metastatic melanoma patients, where the unmet medical need remains high," said Dr. Shu-Hui Liu, Co-founder and CSO of Multitude Therapeutics. "These initial data, together with our previously published preclinical findings*, highlight the potential of AMT-253 to offer meaningful outcome improvement to patients who have exhausted standard-of-care options. We look forward to further clinical confirmation of these results and to fully exploring the potential of this novel ADC for greater patient benefit."

*Shi et al., (2023) Cancer Research 83:3783-95

Poster Presentation Details:

Title: Ongoing Phase I trial results of AMT-253, a first-in-class MUC18-targeting antibody-drug conjugate in patients with melanoma and other advanced solid tumors
Session Title: Developmental therapeutics
Date and Time: October 19th – 09:00-17:00
Poster Number: 997P
Location: Hall 25, Level 2

About AMT-253

AMT-253, a MUC18 ADC, is composed of a proprietary antibody with high MUC18 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is designed to complement the exatecan payload, enabling a stable and homogenous ADC. The payload is a weak substrate for BCRP/P-gp, which are drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, this linker-payload has been shown to have an increased "bystander effect" compared to the equivalent of competitor ADCs**. AMT-253 has a drug-to-antibody ratio of eight. AMT-253 is being evaluated in a Phase I/II study in patients with melanoma and other advanced solid tumors. Additional information on the AUS PhI(NCT05906862) and China PhI/II (NCT06209580) trials can be found at clinicaltrials.gov.

(Press release, Multitude Therapeutics, OCT 19, 2025, View Source [SID1234656798])