On October 19, 2025 Faeth Therapeutics reported results from the international DICE trial, a randomized phase 2 study of sapanisertib (TAK228) plus weekly paclitaxel versus paclitaxel alone in women with platinum-resistant or recurrent epithelial ovarian or fallopian tube cancer. The trial was selected for a Late-Breaking Oral Presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 and met its pre-ordained statistical design and there is sufficient evidence of a positive signal to justify a larger phase 3 design.

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134 patients were enrolled across sites in the UK and Germany. Median age was 62 years and nearly half had received three or more prior therapies. The combination achieved mean progression-free survival (PFS) of 5.8 months compared to 4.0 months with paclitaxel alone, extending time to disease progress by approximately 45 percent. The addition of sapanisertib was associated with a 34% reduction in risk of progression compared to paclitaxel alone (HR=0.66; 90% CI: 0.45–0.96; p=0.07), meeting the trial’s prespecified hazard ratio target of 0.66.

Grade 3/4 adverse events occurred in 7% of patients receiving the combination versus 6.6% for paclitaxel alone. Gastrointestinal toxicities (11.4% vs. 0%) and rash (2.9% vs. 0%) were more common with the combination but were manageable.

"Platinum-resistant ovarian cancer remains one of the toughest conditions we face, with women often cycling through treatments that only briefly hold the disease at bay temporarily," said Jonathan Krell, MD, Ovarian Cancer Action Research Centre, Imperial College London, the study’s lead investigator. "The DICE trial shows that adding an oral targeted agent to weekly paclitaxel can slow progression without added high-grade toxicity, a finding that clearly warrants a phase 3 trial."

"These results reinforce our belief that targeting the metabolism of cancer cells can improve the impact of existing therapies," said Anand Parikh, JD, CEO and co-founder of Faeth Therapeutics. "On the strength of DICE, we see sapanisertib plus paclitaxel as phase 3-ready in ovarian cancer, alongside our ongoing phase 2 in endometrial cancer and planned phase 1b/2 in breast cancer."

Response rate and overall survival analyses are ongoing. The trial is also evaluating biomarkers, including PTEN expression, metabolic signatures, and genomic correlates, to identify patients most likely to benefit from the combination.

About the DICE Trial

DICE (NCT03648489) is a multi-centre randomized phase 2 study comparing weekly paclitaxel alone versus paclitaxel plus sapanisertib in women with platinum-resistant or recurrent ovarian or fallopian tube cancer. The primary endpoint is progression-free survival; secondary endpoints include response rate and overall survival. Translational endpoints include PTEN correlation and exploratory biomarker analyses.

(Press release, Faeth Therapeutics, OCT 19, 2025, View Source [SID1234656805])

On October 19, 2025 Merck and Daiichi Sankyo reported results from the phase 2 (dose optimization) part of the REJOICE-Ovarian01 phase 2/3 trial showed that raludotatug deruxtecan (R-DXd) demonstrated clinically meaningful response rates in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer. These data were presented today during a late-breaking proffered paper session (LBA42) at the 2025 European Society for Medical Oncology (#ESMO25) Congress.

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Raludotatug deruxtecan is a specifically engineered, potential first-in-class CDH6 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada.

The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.1,2 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens, highlighting the need for new treatment options.3

A confirmed objective response rate (ORR) of 50.5% (95% confidence interval [CI]: 40.6-60.3) was observed in patients (n=107) with platinum-resistant ovarian cancer receiving raludotatug deruxtecan across three doses (4.8 mg/kg, 5.6 mg/kg and 6.4 mg/kg) as assessed by blinded independent central review (BICR). There were 3 complete responses (CRs) and 51 partial responses (PRs) seen, and a disease control rate (DCR) of 77.6% (95% CI: 68.5–85.1) was observed.

In patients receiving the 5.6 mg/kg dose (n=36), a confirmed ORR of 50.0% (95% CI: 32.9–67.1) was observed as assessed by BICR with two CRs (5.6%), 16 PRs (44.4%) and a DCR of 80.6% (95% CI: 64.0–91.8). Clinically meaningful tumor responses were seen irrespective of dose and across a range of CDH6 expression levels.

The safety profile of raludotatug deruxtecan observed in REJOICE-Ovarian01 is consistent with safety findings from the phase 1 trial with no new safety signals identified. Nausea, anemia, asthenia and neutropenia were the most common treatment-emergent adverse events (TEAEs) across all doses. Treatment discontinuations due to treatment-related TEAEs occurred in 8.3% (n=3), 0.0% (n=0) and 8.6% (n=3) in the 4.8 mg/kg, 5.6mg/kg and 6.4 mg/kg groups, respectively. Grade 3 or higher treatment-related TEAEs occurred in 27.8% (n=10), 30.6% (n=11), and 48.6% (n=17) of patients in the 4.8 mg/kg (n=36), 5.6 mg/kg (n=36), and 6.4 mg/kg (n=35) groups, respectively.

The most common TEAEs (≥10% of total population) in the 5.6 mg/kg cohort included nausea (69.4%), anemia (58.3%), asthenia (50.0%), neutropenia (44.4%), vomiting (33.3%), constipation (27.8%), decreased appetite (25.0%), thrombocytopenia (19.4%), AST increase (16.7%), diarrhea (16.7%) and leukopenia (13.9%). Four (3.7%) interstitial lung disease (ILD)/pneumonitis events were confirmed as treatment-related across all doses as determined by an independent adjudication committee. The majority of ILD events (one with 5.6 mg/kg, two with 6.4 mg/kg) were low grade (grade 1 or 2). One grade ≥3 (4.8 mg/kg) ILD event was reported. Based on these efficacy and safety results, the 5.6 mg/kg dose has been selected for the phase 3 part of the trial.

"When ovarian cancer becomes resistant to platinum-based chemotherapy, treatment options for patients become limited," said Isabelle Ray-Coquard, MD, PhD, President, ENGOT (European Network of Gynecological Oncology Trial) Group, Trial Leader, National Group of Investigators on the Studies of Ovarian and Breast Cancer (GINECO), and Medical Oncologist, Centre Léon Bérard, Lyon, France. "These promising results from the first part of REJOICE-Ovarian01 suggest that raludotatug deruxtecan may have an important role in treating patients with platinum-resistant ovarian cancer and support further evaluation in the phase 3 portion of this trial."

"In this dose optimization analysis, rapid responses with impressive disease control have been observed with raludotatug deruxtecan across a range of CDH6 expression levels," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "These results, which contributed to the recent Breakthrough Therapy Designation in the U.S., reinforce the potential for raludotatug deruxtecan to become a new treatment option for certain types of patients with platinum-resistant ovarian cancer."

"While we have seen targeted treatment advancements and improved outcomes in ovarian cancer in recent years, there is still a high unmet need for additional options for patients," said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. "CDH6 is highly expressed in ovarian cancer, which underscores the potential of raludotatug deruxtecan to make an impact."

In September 2025, raludotatug deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with bevacizumab.

Median follow-up for the 4.8-mg/kg, 5.6-mg/kg and 6.4-mg/kg cohorts was 5.6 months (95% CI: 4.7–6.3), 5.6 months (95% CI: 4.6–5.8), and 5.2 months (95% CI: 4.9–5.8), respectively. A majority of patients (51.4%) in REJOICE-Ovarian01 received three prior lines of treatment, including bevacizumab (n=89; 83.2%), PARP inhibitor (n=75; 70.1%) and mirvetuximab soravtansine (n=3; 2.8%). As of the data cut-off of February 26, 2025, 66 patients (61.7%) remain on treatment with raludotatug deruxtecan.

Summary of REJOICE-Ovarian01 Results

Efficacy Measure

Raludotatug
Deruxtecan
Across 4.8, 5.6 and 6.4
mg/kg (n=107)

Raludotatug
Deruxtecan
6.4 mg/kg
(n=35)

Raludotatug
Deruxtecan
5.6 mg/kg
(n=36)

Raludotatug
Deruxtecan
4.8 mg/kg
(n=36)

Confirmed ORR, % (95% CI)1

50.5%

(40.6–60.3)

57.1%

(39.4–73.7)

50.0%

(32.9–67.1)

44.4%

(27.9–61.9)

CR, n (%)

3 (2.8%)

0

2 (5.6%)

1 (2.8%)

PR, n (%)

51 (47.7%)

20 (57.1%)

16 (44.4%)

15 (41.7%)

SD, n (%)

42 (39.3%)

10 (28.6%)

15 (41.7%)

17 (47.2%)

PD, n (%)

8 (7.5%)

4 (11.4%)

2 (5.6%)

2 (5.6%)

NE, n (%)

3 (2.8%)

1 (2.9%)2

1 (2.8%)3

1 (2.8%)2

DCR, %

(95% CI)

77.6%

(68.5–85.1)

77.1%

(59.9–89.6)

80.6%

(64.0–91.8)

75.0%

(57.8–87.9)

TTR, weeks, median (range)

7.1 weeks

(5.1–19.1)

7.2 weeks

(5.3–19.1)

6.6 weeks

(5.1–18.3)

7.1 weeks

(5.4–18.7)

Data cutoff: February 26, 2025.

1As accessed by BICR per RECIST 1.1. 2Patient had no baseline tumor assessment by BICR. 3Patient had no adequate post-baseline tumor assessment by BICR.

BICR, blinded independent central review; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SD, stable disease; TTR, time to response.

About REJOICE-Ovarian01
REJOICE-Ovarian01 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan in patients with platinum-resistant, high-grade ovarian, primary peritoneal or fallopian tube cancer, with disease progression following at least one but no more than three prior lines of systemic therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression. Maintenance therapy (e.g., bevacizumab, poly ADP-ribose polymerase [PARP] inhibitors) is considered part of the preceding line of therapy.

The phase 2 part of REJOICE-Ovarian01 is assessing the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg) to identify the recommended dose for the phase 3 part of the trial. The primary endpoint of the phase 2 part of the trial is ORR as assessed by BICR. Key secondary endpoints include ORR as assessed by investigator, DoR, PFS and DCR – all assessed by both BICR and investigator.

The phase 3 part of REJOICE-Ovarian01 is assessing the efficacy and safety of raludotatug deruxtecan at the selected dose (5.6 mg/kg) compared to investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan). The dual primary endpoints of the phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial.

REJOICE-Ovarian01 is expected to enroll approximately 710 patients across Asia, Europe, North America, and Oceania. For more information, please visit ClinicalTrials.gov.

About Ovarian Cancer
More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.4 The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.1,2

The introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines.5 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.3 For patients who develop platinum-resistant ovarian cancer, defined as disease progression less than six months after completion of last platinum-based chemotherapy, prognosis is particularly poor and treatment options are limited.6,7

About CDH6
CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.8 An estimated 65% to 94% of patients with ovarian cancer have tumors that express CDH6.9,10,11 In addition, CDH6 expression is observed more frequently in high-grade serous carcinomas.9, 10,11 There is currently no CDH6 directed medicine approved for treatment of any cancer.

About Raludotatug Deruxtecan
Raludotatug deruxtecan is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

(Press release, Merck & Co, OCT 19, 2025, View Source [SID1234656804])

On October 19, 2025 Daiichi Sankyo reported initial results from the dose escalation part of the first-in-human phase 1/2 trial of DS-3939 demonstrated promising clinical activity in patients with previously treated advanced solid tumors refractory to standard treatment. These data were presented today during a proffered paper session (917O) at the 2025 European Society for Medical Oncology (#ESMO25).

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DS-3939 is a specifically engineered, potential first-in-class tumor-associated mucin-1 (TA-MUC1) directed DXd antibody drug conjugate (ADC) discovered and being developed by Daiichi Sankyo (TSE: 4568).

TA-MUC1 is a tumor-specific transmembrane glycoprotein that is overexpressed in most human epithelial cancers, making it a promising target for cancer therapy.1,2 Currently, there are no TA-MUC1 directed medicines approved for any type of cancer.

Preliminary safety and efficacy results of DS-3939 were reported from the dose escalation part of the phase 1/2 trial in 64 patients with advanced solid tumors, including 16 with non-small cell lung cancer (NSCLC), 12 with pancreatic ductal adenocarcinoma, nine with urothelial carcinoma, eight with ovarian cancer, seven with biliary tract cancer, seven with colorectal cancer and five with breast cancer.

Patients in the dose escalation phase of the study (n=64) received a median of three prior therapies (range, 1-17) for locally advanced/metastatic disease, including more than one-third receiving prior topoisomerase I inhibitor treatment (n=24; 37.5%). As of the data cut-off on August 1, 2025, 15 patients (23.4%) were still being treated with DS-3939.

The safety and tolerability of DS-3939 was evaluated at increasing dose levels from 1.0 mg/kg to 10.0 mg/kg. The most common treatment-emergent adverse events (TEAEs) of any grade in >20% of patients were nausea (60.9%), vomiting (35.9%), fatigue (28.1%), anemia (26.6%), constipation (26.6%), decreased appetite (23.4%), diarrhea (23.4%) and decreased neutrophil count (23.4%). Grade 3 or higher TEAEs occurred in 46.9% of patients (n=30) and the most common (>2%) included decreased neutrophil count (15.6%), anemia (10.9%), pneumonitis (4.7%) and decreased platelet count (3.1%). There were three dose-limited toxicities observed, including one grade 3 anemia needing transfusion (4.0 mg/kg dose), one grade 3 abdominal pain (6.0 mg/kg dose) and one grade 4 decreased platelet count (8.0 mg/kg dose). All grade adjudicated as treatment-related interstitial lung disease (ILD)/pneumonitis occurred in 10.9% (n=7) of patients. The majority of ILD events were low grade (grade 2 [n=6 or 9.4%]) with one grade 3 (n=1 or 1.6%) event as determined by an independent adjudication committee. Following the data cut-off of August 1, 2025, two ILD events were adjudicated as grade 5 and two additional ILD events are pending adjudication.

Preliminary efficacy results were reported across dose levels from 1.0 mg/kg to 10.0 mg/kg of DS-3939. One confirmed complete response was observed in a patient with ovarian cancer and 10 confirmed partial responses were seen in patients with ovarian cancer (n=5), NSCLC (n=4) and breast cancer (n=1). Thirty-nine cases of stable disease were observed in patients with NSCLC (n=11), urothelial carcinoma (n=8), pancreatic ductal adenocarcinoma (n=6), colorectal cancer (n=5), biliary tract cancer (n=4), breast cancer (n=3) and ovarian cancer (n=2) after a median follow-up of 8.8 months (range, 0.6-22.9).

"These initial results are encouraging for patients with advanced solid tumors where treatment options remain limited once standard therapies are no longer effective," said Manish R. Patel, MD, Director of Drug Development, Florida Cancer Specialists and Sarah Cannon Research Institute. "Enrollment continues into the dose expansion part of the trial to help us better understand the potential role DS-3939 may play in treating numerous types of advanced solid tumors."

"These first-in-human results offer preliminary evidence that targeting the novel tumor antigen TA-MUC1 may be a promising treatment approach for multiple types of cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Additionally, these results represent the sixth antibody drug conjugate from the pipeline of Daiichi Sankyo with encouraging early phase data further demonstrating the portability of our DXd antibody drug conjugate technology to new tumor targets."

About the Phase 1/2 Trial
The two-part, multicenter, open-label, first-in-human phase 1/2 trial is assessing the safety and efficacy of DS-3939 in patients with locally advanced, metastatic or unresectable solid tumors not amenable to standard of care treatment for each tumor type.

The first part of the trial (dose escalation) assessed the safety and tolerability of increasing doses of DS-3939 to determine the maximum tolerated dose and/or the recommended doses for expansion (RDEs) in patients with locally advanced, metastatic or unresectable solid tumors.

The second part of the trial (dose expansion) consists of multiple expansion cohorts to assess the safety and efficacy of DS-3939. The trial will evaluate safety endpoints, including dose-limiting toxicities and adverse events, and efficacy endpoints, including objective response rate, disease control rate, duration of response, time to response, progression-free survival and overall survival. Pharmacokinetic and biomarker endpoints also will be assessed.

The trial is ongoing and enrolling patients across multiple tumor types at sites globally, including Asia, Europe and North America. For more information, please visit ClinicalTrials.gov.

About TA-MUC1
TA-MUC1, a tumor-specific transmembrane glycoprotein, is a molecular target that is expressed across a broad range of solid tumors, but has limited expression in normal human tissues.1 Based on the overexpression of TA-MUC1 in solid tumors, it is an attractive target for cancer therapy.2 Currently, there are no TA-MUC1 directed therapies approved for any type of cancer.

About DS-3939
DS-3939 is an investigational, potential first-in-class TA-MUC1 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DS-3939 is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo. DS-3939 is comprised of a humanized anti-TA-MUC1 antibody, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

(Press release, Daiichi Sankyo, OCT 19, 2025, View Source [SID1234656803])

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.

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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.

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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])