On October 20, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported new long-term data highlighting the sustained survival benefits of KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in treating non-small cell lung cancer (NSCLC). The results are based on the exploratory five-year analyses of KEYNOTE-671 evaluating KEYTRUDA as part of a neoadjuvant followed by adjuvant (perioperative) treatment regimen for patients with resectable NSCLC; and the eight-year analyses of KEYNOTE-024 and -042 and the 10-year analyses of KEYNOTE-001 and -010 evaluating KEYTRUDA as monotherapy in certain patients with locally advanced or metastatic NSCLC.

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"These long-term data mark a milestone for patients and their families and build upon the transformative progress we’ve already made in non-small cell lung cancer," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "Across the spectrum of earlier to advanced stages of disease, these results support the long-term survival benefit of KEYTRUDA in certain patients with NSCLC. We look forward to continued advancements and possibilities for KEYTRUDA in cancer treatment."

In the exploratory five-year follow-up data from the Phase 3 KEYNOTE-671 trial, KEYTRUDA in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery continued to show clinically meaningful improvements in overall survival (OS) and event-free survival (EFS) outcomes in certain patients with resectable stage II, IIIA or IIIB NSCLC, compared to neoadjuvant placebo plus chemotherapy followed by adjuvant placebo alone. The hazard ratio (HR) for OS for the KEYTRUDA regimen versus the chemotherapy-placebo regimen was 0.74 (95% CI, 0.59-0.92). For EFS, the HR for the KEYTRUDA regimen versus the chemotherapy-placebo regimen was 0.58 (95% CI, 0.48-0.69).

"The five-year benefit demonstrated across overall survival and event-free survival from KEYNOTE-671 supports the continued use of this pembrolizumab-based perioperative regimen as a standard of care for patients with resectable, earlier-stage non-small cell lung cancer," said Dr. Heather Wakelee, principal investigator for KEYNOTE-671, thoracic medical oncologist. "These consistent results are impactful, as they reflect the importance of intervening for certain patients with earlier stages of non-small cell lung cancer." Wakelee is also a professor of medicine at Stanford Medicine.

In the exploratory eight-year analyses from KEYNOTE-024 and KEYNOTE-042 and the exploratory 10-year analyses from KEYNOTE-001 and KEYNOTE-010, KEYTRUDA continued to improve OS in patients with locally advanced or metastatic NSCLC compared to chemotherapy.

In KEYNOTE-001, the median OS for patients receiving KEYTRUDA was 13.2 months (95% CI, 10.5-15.3) in those with any Tumor Proportion Score (TPS) and a median OS of 17.3 months (95% CI,13.7-24.8) in those with a TPS ≥50%. KEYNOTE-001 did not compare KEYTRUDA to another agent or placebo.
In KEYNOTE-010, the median OS for patients receiving KEYTRUDA with a TPS ≥1% was 11.8 months (95% CI, 10.3-13.0) versus 8.3 months (95% CI, 7.5-9.5) for chemotherapy (HR=0.66 [95% CI, 0.58-0.76]). For patients receiving KEYTRUDA, with a TPS ≥50%, the median OS was 16.6 months (95% CI, 12.1-21.2) versus 8.2 months (95% CI, 6.4-9.8) for chemotherapy (HR=0.55 [95% CI, 0.44-0.68]).
In KEYNOTE-024, the median OS for patients receiving KEYTRUDA with a TPS ≥50% was 26.3 months (95% CI,18.3-40.4) versus 13.4 months (95% CI, 9.4-18.3) for chemotherapy (HR=0.65 [95% CI, 0.50-0.83]).
In KEYNOTE-042, the median OS for patients receiving KEYTRUDA with a TPS ≥1% was 16.4 months (95% CI, 14.0-19.6) versus 12.1 months (95% CI, 11.3-13.3) for chemotherapy (HR=0.78 [95% CI, 0.69-0.88]). For patients receiving KEYTRUDA with a TPS ≥50%, the median OS was 20.0 months (95% CI, 15.9-24.2) versus 12.2 months (95% CI, 10.4-14.6) for chemotherapy (HR=0.70 [95% CI, 0.59-0.83]).
Participants from KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042 who achieved a complete response after taking KEYTRUDA and then had progressive disease were eligible for a subsequent anti-cancer therapy including a second course of KEYTRUDA monotherapy.

Additional details about the study designs and results from KEYNOTE-671, KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042, including selected results of previously reported primary analyses, are described below.

"Historically, patients with advanced non-small cell lung cancer faced a poor prognosis, with long-term survival considered unlikely," said Edward B. Garon, MD, MS, professor of medicine, principal investigator for KEYNOTE-001, David Geffen School of Medicine, the University of California, Los Angeles. "The long-term results from these four trials show that pembrolizumab has helped change what certain patients with advanced NSCLC can hope to achieve."

To date, KEYTRUDA monotherapy or combination regimens have demonstrated sustained survival benefits of five years or more across multiple types of cancer, including certain types of metastatic NSCLC (KEYNOTE-189, KEYNOTE-407), melanoma (KEYNOTE-006, KEYNOTE-054), advanced head and neck (KEYNOTE-048), bladder (KEYNOTE-045) and endometrial (KEYNOTE-775) cancers.

The late-breaking five-year data from KEYNOTE-671 were presented during a mini oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 (Presentation #LBA67). The eight-year data from KEYNOTE-024 and KEYNOTE-042 and 10-year data from KEYNOTE-001 and KEYNOTE-010 were presented during a poster session at the ESMO (Free ESMO Whitepaper) Congress 2025 (Presentation #3208P).

Study design and additional five-year data from KEYNOTE-671

KEYNOTE-671 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial (ClinicalTrials.gov; NCT03425643) evaluating KEYTRUDA in combination with neoadjuvant chemotherapy, followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent, versus placebo plus neoadjuvant chemotherapy, followed by resection and adjuvant placebo, in patients with resectable stage II, IIIA or IIIB (T3-4N2) NSCLC (per the eighth edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual). The trial’s dual primary endpoints are EFS and OS. Key secondary endpoints include pathologic complete response (pCR) and major pathological response (mPR). The study enrolled 797 patients who were randomly assigned (1:1) to receive either:

KEYTRUDA (200 mg intravenously [IV] every three weeks) plus chemotherapy (cisplatin [75 mg/m2 , IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2 , IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4-12 weeks following surgery, KEYTRUDA (200 mg) was administered every three weeks for up to 13 cycles, or;
Placebo (saline IV every three weeks) plus chemotherapy (cisplatin [75 mg/m2 , IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4‑12 weeks following surgery, placebo was administered every three weeks for up to 13 cycles.
After a median follow-up of 60.4 months (range, 42.6-85.8), the five-year OS rate was 64.6% (95% CI, 59.5%-69.2%) for the KEYTRUDA regimen versus 53.6% (95% CI, 48.3%-58.6%) for the chemotherapy-placebo regimen. Median OS was not reached (NR) (95% CI, NR-NR) for patients who received the KEYTRUDA regimen versus 70.7 months (95% CI, 53.7-NR) for patients who received the chemotherapy-placebo regimen.

The five-year EFS rate was 49.9% (95% CI, 44.6%-55.0%) for the KEYTRUDA regimen versus 26.5% (95% CI, 21.7%-31.5%) for the chemotherapy-placebo regimen. Median EFS was 57.1 months (95% CI, 38.0-NR) for patients who received the KEYTRUDA regimen versus 18.4 months (95% CI, 14.8-22.1) for patients who received the chemotherapy-placebo regimen.

At the five-year follow-up analysis, Grade ≥3 treatment-related adverse events (TRAEs) occurred in 45.2% of patients receiving the KEYTRUDA regimen and 37.8% of patients receiving the chemotherapy-placebo regimen. Grade ≥3 immune-mediated adverse events (AEs) and infusion reactions occurred in 6.3% of patients receiving the KEYTRUDA regimen and 1.8% of patients receiving the chemotherapy-placebo regimen.

At the study’s previously reported primary analysis, KEYNOTE-671 showed that treatment with the KEYTRUDA regimen reduced the risk of death by 28% (HR=0.72 [95% CI, 0.56-0.93]; p=0.0103) versus the chemotherapy-placebo regimen. For patients who received the KEYTRUDA regimen, median OS was not reached (95% CI, NR-NR) versus 52.4 months (95% CI, 45.7-NR) for patients who received the chemotherapy-placebo regimen. Additionally, the KEYTRUDA regimen reduced the risk of EFS events by 42% (HR=0.58 [95% CI, 0.46-0.72]; p<0.0001) versus the chemotherapy-placebo regimen. For patients who received the KEYTRUDA regimen, median EFS was not reached (95% CI, 34.1-NR) versus 17.0 months (95% CI, 14.3-22.0) for patients who received the chemotherapy-placebo regimen.

(Press release, Merck & Co, OCT 20, 2025, View Source [SID1234656818])

Long-term follow-up data from exploratory analyses of KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042

In KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042, KEYTRUDA continued to improve OS compared to chemotherapy. In these studies, data showed KEYTRUDA improved OS compared to chemotherapy in patients whose tumors expressed PD-L1 (TPS ≥50%). Overall survival results from these long-term follow-up analyses showed:

KEYTRUDA

Chemotherapy

KEYNOTE-001a,b,c

Any TPS

n/N = 54/550

N/A

10y OS rate (95% CI), %

11.3% (8.5%-14.5%)

N/A

Median OS (95% CI), months

13.2 (10.5-15.3)

N/A

TPS ≥50%

n/N = 25/165

N/A

10y OS rate

19.3% (13.1%-26.5%)

N/A

Median OS (95% CI), months

17.3 (13.7-24.8)

N/A

KEYNOTE-010b,d

TPS ≥1%

n/N = 53/690

n/N = 9/343

10y OS rate

9.3% (7.0%-12.1%)

1.9% (0.7%-4.6%)

Median OS (95% CI), months

11.8 (10.3-13.0)

8.3 (7.5-9.5)

HR (95% CI)

0.66 (0.58–0.76)

TPS ≥50%

n/N = 35/290

n/N = 6/152

10y OS rate

15.5% (11.1%-20.5%)

2.7% (0.7%-7.4%)

Median OS (95% CI), months

16.6 (12.1-21.2)

8.2 (6.4-9.8)

HR (95% CI)

0.55 (0.44-0.68)

KEYNOTE-024a

TPS ≥50%

n/N = 36/154

n/N = 14/151

8y OS rate

24.3% (17.6%-31.5%)

12.8% (7.6%-19.3%)

Median OS (95% CI), months

26.3 (18.3-40.4)

13.4 (9.4-18.3)

HR (95% CI)

0.65 (0.50-0.83)

KEYNOTE-042a

TPS ≥1%

n/N = 66/637

n/N = 27/637

8y OS rate

12.0% (9.5%-14.8%)

4.7% (3.1%-6.9%)

Median OS (95% CI), months

16.4 (14.0-19.6)

12.1 (11.3-13.3)

HR (95% CI)

0.78 (0.69-0.88)

TPS ≥50%

n/N = 41/299

n/N = 13/300

8y OS rate

16.6% (12.5%-21.1%)

6.8% (4.1%-10.5%)

Median OS (95% CI), months

20.0 (15.9-24.2)

12.2 (10.4-14.6)

HR (95% CI)

0.70 (0.59-0.83)

n/N, number of patients in KEYNOTE-587/number of patients in parent study.

afirst-line therapy

bsecond-line+ therapy

cIn KEYNOTE-001, KEYTRUDA was not compared to any other agent or placebo.

dtwo doses of pembrolizumab treatment were combined for these analyses

Limited additional lung cancer-specific deaths occurred since the previously reported five-year data across all four trials.

At the conclusion of these initial studies, participants were eligible to transition to the KEYNOTE-587 extension study for long-term follow-up. The primary endpoint for KEYNOTE-587 is OS. For patients in KEYNOTE-587, the median time from first treatment in KEYNOTE-001 or randomization in KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042 to data cutoff was 124.6 months (range, 118.5-142.2), 115 months (range, 108.8-124.6), 106.4 months (range, 102.4-114.3) and 99 months (range, 86.6-110.2), respectively.

Study design and additional data from KEYNOTE-001

Ten-year outcomes for KEYTRUDA were measured in the Phase 1b KEYNOTE-001 trial (ClinicalTrials.gov; NCT01295827), which evaluated 550 patients with treatment-naïve or previously treated advanced NSCLC. Patients received 2 mg/kg IV of KEYTRUDA every three weeks or 10 mg/kg IV of KEYTRUDA every two weeks or every three weeks. The primary endpoint was overall response rate (ORR) and secondary endpoints included progression-free survival (PFS) and OS.

At the study’s previously reported primary analysis, KEYNOTE-001 showed that KEYTRUDA demonstrated an ORR of 41% in patients with a TPS ≥50%; all responses were partial responses (95% CI, 29-54). Of the patients who responded, 84% continued to respond to treatment with KEYTRUDA, including 11 patients with ongoing responses of six months or longer.

Study design and additional data from KEYNOTE-010

Ten-year outcomes for KEYTRUDA were measured in the Phase 2/3 KEYNOTE-010 trial (ClinicalTrials.gov; NCT01905657), which evaluated patients with metastatic NSCLC whose tumors expressed PD-L1 (TPS ≥1%) that had progressed after platinum-containing chemotherapy and, if appropriate, targeted therapy for EGFR or ALK genomic tumor aberrations. The trial enrolled 1,033 patients who were randomized (1:1:1) to receive 2 mg/kg IV or 10 mg/kg IV of KEYTRUDA every three weeks or chemotherapy (docetaxel) every three weeks. The primary endpoints for this trial were OS and PFS, and secondary endpoints included ORR and duration of response (DOR).

At the study’s previously reported primary analysis, KEYNOTE-010 showed that 2 mg/kg of KEYTRUDA reduced the risk of death by 29% (HR=0.71 [95% CI, 0.58-0.88]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of death by 39% (HR=0.61 [95% CI, 0.49-0.75]; p<0.001) in patients with a TPS ≥1% versus chemotherapy. Two mg/kg of KEYTRUDA reduced the risk of disease progression or death by 12% (HR=0.88 [95% CI, 0.73-1.04]; p=0.068) and 10 mg/kg of KEYTRUDA reduced the risk of disease progression or death by 21% (HR=0.79 [95% CI, 0.66-0.94]; p=0.005) in patients with a TPS ≥1% versus chemotherapy. Additionally, the analysis showed that 2 mg/kg of KEYTRUDA reduced the risk of death by 46% (HR=0.54 [95% CI, 0.38-0.77]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of death by 50% (HR=0.50 [95% CI, 0.36-0.70]; p<0.001) in patients with a TPS ≥50% versus chemotherapy. Two mg/kg of KEYTRUDA reduced the risk of disease progression or death by 42% (HR=0.58 [95% CI, 0.43-0.77]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of disease progression or death by 41% (HR=0.59 [95% CI, 0.45-0.78]; p<0.001) in patients with a TPS ≥50% versus chemotherapy.

Study design and additional data from KEYNOTE-024

Eight-year outcomes for KEYTRUDA were measured in the Phase 3 KEYNOTE-024 trial (ClinicalTrials.gov; NCT02142738), which evaluated patients with previously untreated metastatic NSCLC whose tumors express high levels of PD-L1 (TPS ≥50%) with no EGFR or ALK genomic tumor aberrations. The trial enrolled 305 patients who were randomized (1:1) to receive 200 mg of KEYTRUDA every three weeks or platinum-based chemotherapy. The primary endpoint for this trial was PFS, and secondary endpoints included OS and ORR. In this study, 10.3% (209) of patients transitioned to KEYNOTE-587.

At the study’s previously reported primary analysis, KEYNOTE-024 showed that KEYTRUDA reduced the risk of disease progression or death by 50% (HR=0.50 [95% CI, 0.37-0.68]; p<0.001) versus chemotherapy. Additionally, KEYTRUDA reduced the risk of death by 40% (HR=0.60 [95% CI, 0.41-0.89]; p=0.005) versus chemotherapy.

Study design and additional data from KEYNOTE-042

Eight-year outcomes for KEYTRUDA were measured in the Phase 3 KEYNOTE-042 trial (ClinicalTrials.gov; NCT02220894), which evaluated patients with stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors expressed PD-L1 (TPS ≥1%) and who had not received prior systemic treatment for metastatic NSCLC. The trial enrolled 1,251 patients who were randomized (1:1) to receive 200 mg of KEYTRUDA every three weeks or platinum-based chemotherapy. The primary endpoint for this trial was OS in patients with a TPS ≥50%, ≥20% or ≥1% and secondary endpoints included PFS and ORR as assessed by blinded independent central review (BICR) according to RECIST v1.1 in patients with a TPS ≥50%, ≥20% or ≥1%. In this study, 4.4% (50) of patients transitioned to KEYNOTE-587.

At the study’s previously reported primary analysis, KEYNOTE-042 showed that KEYTRUDA reduced the risk of death by 31% (HR=0.69 [95% CI, 0.56-0.85]; p=0.0006) in patients with a TPS ≥50% and by 19% (HR=0.81 [95% CI, 0.71-0.93]; p=0.0036) in patients with a TPS ≥1% versus chemotherapy. Median OS was 20.0 months (95% CI, 15.4-24.9) for KEYTRUDA in patients with a TPS ≥50% versus 12.2 months (95% CI, 10.4-14.2) for chemotherapy, and 16.7 months (95% CI, 13.9-19.7) for KEYTRUDA in patients with a TPS ≥1% versus 12.1 months (95% CI, 11.3-13.3) for chemotherapy.

About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2025, the overall five-year survival rate for patients diagnosed with lung cancer was 27% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.

On October 20, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported final results from Part B of the DeFianCe study (NCT05480306), a Phase 2 study of sirexatamab (DKN-01), an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy (Sirexatamab Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease. The final clinical results were presented on behalf of the DeFianCe study investigators by Zev Wainberg, MD, Professor of Medicine and Co-Director of the GI Oncology Program at UCLA in a Mini Oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany.

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"Circulating DKK1 is a negative prognostic factor and elevated in patients with advanced, metastatic CRC. The data presented at ESMO (Free ESMO Whitepaper) demonstrate that sirexatamab, which binds to and removes free DKK1, has significant potential to provide a survival benefit for CRC patients who have high DKK1 levels and who are likely to have poor outcomes receiving the current standard of care alone," said Dr. Wainberg. "Sirexatamab has the potential to be a valuable addition to the CRC treatment paradigm as a targeted therapeutic for patients with high DKK1 and should move forward to be evaluated in a biomarker-focused registrational trial."

The DeFianCe study was a two part, open-label, multi-country study. Part A of the DeFianCe study enrolled 33 patients, including a significant number of patients who had early progression on first-line therapy, previous exposure to bevacizumab, tumors with RAS mutations, or liver and lung metastases. The study expanded into a 188 patient Part B randomized controlled trial. The primary objective of the study was progression-free survival PFS. Secondary objectives included objective response rate (ORR), duration of response, and overall survival (OS). A key pre-defined exploratory population was those patients who had high levels of circulating DKK1, as measured by a biomarker assay.

Key Part B DeFianCe Study Findings:

· Across the DKK1-high (upper median) patients (n=88):
o ORR was 38.0% in the Sirexatamab Arm compared to 23.7% ORR in the Control Arm.
o mPFS was 9.03 months in the Sirexatamab Arm compared to 7.06 months in the Control Arm, Hazard Ratio (HR) 0.61, p-value = 0.0255.
o mOS was not reached in the Sirexatamab Arm compared to 14.39 months in the Control Arm, HR 0.42, p-value = 0.0118.

· Across the DKK1-high (upper quartile) patients (n=44):
o ORR was 44.0% in the Sirexatamab Arm compared to 15.8% ORR in the Control Arm.
o mPFS was 9.36 months in the Sirexatamab Arm compared to 5.88 months in the Control Arm, HR 0.46, p-value = 0.0168.
o mOS was not reached in the Sirexatamab Arm compared to 9.66 months in the Control Arm, HR 0.17, p-value < 0.001.

· In the full intent-to-treat population (n=188):
o ORR was 35.1% in the Sirexatamab Arm compared to 26.6% ORR in the Control Arm.
o mPFS was 9.2 months in the Sirexatamab Arm compared to 8.3 months in the Control Arm, HR 0.84, p-value = 0.1712.
o Event-free rate favors Sirexatamab Arm beginning at month 9 (53 vs 47%) with further separation at month 12 (34 vs 23%).

· Sirexatamab, in combination with chemotherapy and bevacizumab, was safe and well tolerated
o Overall treatment-emergent adverse effects (TEAE) profile was similar between the Sirextamab and Control Arms, suggesting sirexatamab did not impact the safety profile when combined with the standard of care.

"The DeFianCe study results demonstrate the significant potential of sirexatamab in patients with advanced CRC. Patients with this aggressive cancer, particularly those with high DKK1 levels, have poor overall survival outcomes and few promising second-line or later options," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "Sirexatamab has repeatedly demonstrated its potential as a novel, first-in-class antibody targeting DKK1 that provides deep and durable benefit for patients in desperate need of new therapies. With support from a recently completed financing, Leap plans to engage with regulatory authorities over the registrational path for sirexatamab in CRC and to optimize the DKK1 biomarker diagnostic test that could be used to identify these CRC patients with poor prognosis."

(Press release, Leap Therapeutics, OCT 20, 2025, View Source [SID1234656817])

On October 20, 2025 IMUNON, Inc. (Nasdaq: IMNN), a clinical-stage company in Phase 3 development with its DNA-mediated immunotherapy, reported that it will host an R&D Day for investors at the Harvard Club (35 West 44th Street) in New York City on November 10, 2025, beginning at 8:00 a.m. ET.

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The investor event will feature ovarian cancer thought leaders, principal investigators from the Company’s Phase 3 OVATION 3 Study and Phase 2 minimal residual disease (MRD) clinical trial, conducted in partnership with Break Through Cancer Foundation, statistical experts and members of IMUNON’s management team, delivering updates on new IMNN-001 data and discussing progress with the OVATION 3 Study and IMNN-001’s potential role in transforming the treatment landscape for women with advanced ovarian cancer. There will be a live Q&A session and networking opportunities with the speakers and IMUNON management team following the formal presentations.

Featured Presentations and Speakers:

Title: Advancing Ovarian Cancer Care: IMNN-001’s Potential to Transform the Microtumor Environment from Cold to Hot in Phase 3
Presenter: Premal H. Thaker, M.D., David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Chief of Gynecologic Oncology, Director of Gynecologic Oncology Clinical Research, Professor in Gynecologic Oncology, Washington University School of Medicine

Title: Unveiling Progress: Safety, Tolerability, and Translational Insights for IMNN-001
Presenter: Amir Jazaeri, M.D., Vice Chair for Clinical Research, Director, Gynecologic Cancer Immunotherapy Program, Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center
Title: OVATION 3 Probability of Success & the Statistical Properties of Phase 3 Trial Design
Presenter: Giorgio Paulon, Ph.D., Director & Senior Statistical Scientist, Berry Consultants, LLC
Title: Phase 3 OVATION 3 Trial Update
Presenter: Douglas V. Faller, M.D., Ph.D., Chief Medical Officer, IMUNON

(Press release, IMUNON, OCT 20, 2025, View Source [SID1234656816])

On October 20, 2025 Immatics N.V. (NASDAQ: IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical company and the global leader in precision targeting of PRAME, reported the presentation of updated data from 16 patients with metastatic uveal melanoma treated with anzu-cel PRAME cell therapy.

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The uveal melanoma data from the ongoing Phase 1b trial will be presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 during the Presidential Symposium III by Sapna Patel, M.D., Professor of Medicine, University of Colorado Cancer Center. The slides are accessible in the ‘Events & Presentations’ section of the Investors & Media section of the Company’s website.

"Patients with metastatic uveal melanoma face a poor prognosis and represent a population in need of better outcomes, given the limited options currently available," said Sapna Patel, M.D. "I believe the results with anzu-cel presented today signal a much-needed breakthrough for patients with metastatic uveal melanoma. These findings highlight the potential of anzu-cel to redefine the treatment paradigm for uveal melanoma and bring new hope to patients who urgently need more effective options."

"Our goal is to leverage every opportunity to bring innovative PRAME therapies to patients with limited treatment options," said Cedrik Britten, M.D., Chief Medical Officer at Immatics. "The continued strong clinical data presented today reinforce our conviction in maximizing the potential of our PRAME cell therapy, anzu-cel, and expanding its development into metastatic uveal melanoma, a rare cancer with very high unmet medical need. We are excited to further execute on our PRAME franchise and bring meaningful progress to patients in need."

Presidential Symposium III Presentation Summary – Anzu-cel Phase 1b Trial

Patient Population: Difficult-to-treat patient population with metastatic uveal melanoma

As of September 24, 2025, 16 patients with metastatic uveal melanoma were administered a one-time infusion of anzu-cel at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR T cells) as part of the anzu-cel Phase 1b dose expansion. Patients received a median infused TCR T-cell dose of ~4 billion (range 1.62 – 8.43 billion TCR T cells) and had a median of 2 lines of prior systemic treatments. Patients had a median target lesion sum of a diameter of 103 mm (ranging from 31 to 210 mm), and 81% of patients had liver and extrahepatic metastasis.

Anti-tumor Activity and Durability: Continued strong anti-tumor activity and durability of anzu-cel PRAME cell therapy

Updated data of a one-time infusion of anzu-cel PRAME cell therapy demonstrated promising benefit in a difficult-to-treat population with limited effective treatment options:

Confirmed objective response rate (cORR) of 67% (10/151)
Disease control rate (DCR) of 88% (14/16)
Median duration of response (mDOR) of 11 months (min 4.4, max 31.6 months)
Median progression-free survival (mPFS) of 8.5 months (min 1.4, max 32.9) at a mFU of 10.4 months. The PFS rate was 69% at six months and 39% at 12 months
Median overall survival (mOS) not reached (min 4.3+, max 34.2+ months) at a mFU of 14.3 months. The OS rate was 71% at 12 months

Anti-tumor activity was observed in liver and extrahepatic metastases, including lung, lymph node, abdomen/peritoneum and others. 14/16 patients had target lesions in the liver and treatment with anzu-cel led to a median shrinkage in liver target lesion size of 49.6%.

Notably, 11 out of the 16 patients received a TCR bispecific (ten gp-100-targeting, one PRAME-targeting) as prior systemic treatment line, and thereof, six achieved a confirmed partial response, one a partial response and three stable disease. These results demonstrate anti-tumor activity of anzu-cel in patients who received prior TCR-based therapies.

Safety: Favorable tolerability in uveal melanoma, generally consistent with full anzu-cel tolerability profile

The most frequent treatment-emergent adverse events (TEAs) were anticipated cytopenias associated with lymphodepletion. Expected and manageable cytokine release syndrome (CRS) was mostly Grade 1 or 2, which is consistent with the mechanism of action (Grade 1: 37.5%, Grade 2: 43.8%, Grade 3: 18.8%, Grade 4: 0%). No patients experienced long-term CRS, and most CRS was resolved by day 14. No anzu-cel-related Grade 5 events were observed.

Tolerability in the uveal melanoma subset was generally consistent with the full anzu-cel tolerability profile in the Phase 1b.

Development Path for Anzu-cel in Metastatic Uveal Melanoma

Based on the promising clinical data in patients with metastatic uveal melanoma, Immatics has initiated a Phase 2 cohort with approximately 30 uveal melanoma patients planned. The cohort is being conducted at select centers in the U.S. and Germany with deep expertise in uveal melanoma. Given the high prevalence of PRAME expression in uveal melanoma, prospective PRAME testing is no longer required for inclusion in the clinical trial.

The consistent tolerability, anti-tumor activity and pharmacokinetic profile of anzu-cel across both uveal and cutaneous melanoma provide a strong rationale for pursuing a parallel late-stage development strategy to serve both patient populations.

About PRAME
PRAME is a target expressed in more than 50 cancers. Immatics is the global leader in precision targeting of PRAME and has the broadest PRAME franchise with the most PRAME indications and modalities. The Immatics PRAME franchise currently includes three product candidates, two therapeutic modalities and a combination therapy that target PRAME: anzu-cel (IMA203) PRAME cell therapy, IMA203CD8 PRAME cell therapy (GEN2), IMA402 PRAME bispecific, anzu-cel in combination with Moderna’s PRAME cell therapy enhancer.

About Anzu-cel (IMA203) PRAME Cell Therapy
Anzu-cel (anzutresgene autoleucel; IMA203) is a PRAME-directed TCR T-cell therapy engineered to recognize an intracellular PRAME-derived peptide presented by HLA-A*02:01 on the cell surface and initiate a potent and specific anti-tumor response. Anzu-cel PRAME cell therapy is currently being evaluated in a registration-enabling randomized controlled Phase 3 trial, "SUPRAME," in patients with unresectable or metastatic cutaneous melanoma who have disease progression on or after treatment with at least one checkpoint inhibitor. In parallel, the Phase 1b clinical trial in patients with PRAME cancers is ongoing with a focus on uveal melanoma.

(Press release, Immatics, OCT 20, 2025, View Source [SID1234656815])

On October 20, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported detailed results from STELLAR-303, a global phase 3 pivotal trial evaluating zanzalintinib in combination with atezolizumab (Tecentriq) versus regorafenib in patients with previously treated non-microsatellite instability (MSI)-high metastatic colorectal cancer (CRC). As previously announced, the study met one of its dual primary endpoints, demonstrating a 20% reduction in the risk of death with the combination in the intention-to-treat (ITT) population at the final analysis (stratified hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.69-0.93; P=0.0045). At a median follow-up of 18.0 months, median overall survival (OS) in the ITT population was 10.9 months with zanzalintinib in combination with atezolizumab versus 9.4 months with regorafenib. Detailed findings from the study, including OS and progression-free survival (PFS) in the ITT population and in the subset of patients without liver metastases, are being presented today at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress during the Proffered Paper Session 2: GI Tumours, Lower Digestive at 9:25 a.m. CEST and simultaneously published in The Lancet.

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"While treating non-MSI-high metastatic colorectal cancer remains a challenge, the combination of zanzalintinib and atezolizumab has shown consistent benefits across key subgroups of patients," said Anwaar Saeed, M.D., Section Chief of Gastrointestinal Oncology at the University of Pittsburgh, Director of the Gastrointestinal Disease Center at UPMC Hillman Cancer Center and a lead investigator of the trial. "STELLAR-303 is the first immunotherapy-based phase 3 trial that demonstrated improved overall survival with a differentiated kinase inhibitor compared to a standard of care in this patient population. The survival benefit was demonstrated early and was consistent throughout the trial, underscoring the combination’s potential for patients in need of a new and effective treatment option after disease progression."

An OS benefit with the combination was consistently observed across pre-specified subgroups, including geographic region, RAS status, liver involvement and prior anti-VEGF therapy, as presented in Table 1 below. The 12- and 24-month landmark OS estimates were 46% (95% CI: 41-51) and 20% (95% CI: 15-26), respectively, for the combination of zanzalintinib and atezolizumab, and 38% (95% CI: 34-43) and 10% (95% CI: 6-16), respectively, for regorafenib.

TABLE 1

Median OS, months (95% CI)

HR (95% CI)

Zanzalintinib + Atezolizumab

Regorafenib

Geographic region

Asia

11.5 (9.2-13.7)

8.8 (7.8-10.4)

0.77 (0.59-1.00)

Rest of the world

10.9 (9.3-12.3)

9.8 (8.3-10.9)

0.82 (0.68-0.99)

RAS status

Wild type

12.0 (10.1-14.6)

10.4 (8.7-12.3)

0.79 (0.61-1.01)

Mutant

10.3 (9.0-11.9)

8.7 (8.1-9.8)

0.80 (0.66-0.98)

Active liver metastases

Presence

8.9 (8.0-9.9)

7.7 (6.5-8.5)

0.78 (0.65-0.94)

Absence

15.9 (13.5-17.6)

12.8 (10.9-15.5)

0.77 (0.59-1.01)

Prior anti-VEGF antibody treatment

Yes

10.6 (9.3-12.5)

8.8 (8.3-9.9)

0.80 (0.68-0.95)

No

11.5 (8.7-13.5)

11.1 (9.5-12.6)

0.80 (0.56-1.15)

OS = overall survival; CI = confidence interval; HR = hazard ratio; VEGF = vascular endothelial growth factor

Data pertaining to the other dual primary endpoint, OS in patients without liver metastases (non-liver metastases, NLM), were immature at the data cutoff. A prespecified interim analysis showed a trend in OS favoring the combination (15.9 months versus 12.8 months; stratified HR: 0.79; 95% CI: 0.61-1.03; P=0.0875) at a median follow-up of 16.8 months. The trial will proceed to the planned final analysis for this endpoint.

"These detailed results from STELLAR-303 provide further insight into the combination of zanzalintinib and atezolizumab as a potential new option to extend survival in patients with previously treated metastatic colorectal cancer," said Dana T. Aftab, Ph.D., Executive Vice President, Research and Development, Exelixis. "Before the end of this year, we intend to complete the submission of our first new drug application for zanzalintinib as we work toward bringing this combination regimen to a patient community seeking a new and chemotherapy-free option. These data, along with our robust clinical trial program, underscore the progress we are making toward our goal of increasing the scope and scale of the solid tumor types zanzalintinib may help address."

A trend for improvement in PFS with the combination was also observed in the ITT population (stratified HR: 0.68 [95% CI: 0.59–0.79]; median, 3.7 [95% CI: 3.5–3.8] months versus 2.0 [95% CI: 1.9–2.6] months), though statistical superiority cannot be claimed at this time due to the prespecified hierarchical testing strategy. The trend for PFS improvement with zanzalintinib in combination with atezolizumab versus regorafenib was consistent across subgroups.

The safety profiles of zanzalintinib in combination with atezolizumab and of regorafenib were generally consistent with what has been previously observed, and no new safety signals were identified. Grade 3/4 treatment-related adverse events (AEs) occurred in 59% of patients receiving zanzalintinib in combination with atezolizumab and 37% of patients receiving regorafenib. AEs leading to discontinuation of all study treatment occurred in 18% versus 15% of patients, respectively. The most common grade 3/4 treatment-related AEs were hypertension (15% versus 9%, respectively), fatigue (6% versus 2%), diarrhea (6% versus 2%) and proteinuria (6% versus 2%). Deaths considered related to treatment by investigators were two for zanzalintinib, two for atezolizumab, one for the combination and one for regorafenib.

About STELLAR-303
STELLAR-303 (NCT05425940) is a global, multicenter, randomized, phase 3, open-label study that randomized patients 1:1 to either zanzalintinib in combination with atezolizumab (n=451) or regorafenib (n=450). The study includes patients with previously treated non-MSI-high metastatic CRC. The dual primary endpoints of the study are OS in the ITT population and in the NLM subgroup of patients. The ITT population consisted of all randomized patients, regardless of the presence of liver metastases. The NLM subgroup consisted of patients who did not have active liver metastases at baseline as determined by investigator assessment. Secondary endpoints include PFS, objective response rate and duration of response in the ITT population and in the NLM subgroup of patients. More information about the trial is available at ClinicalTrials.gov.

About Zanzalintinib
Zanzalintinib is a novel oral kinase inhibitor that inhibits the activity of the TAM kinases (TYRO3, AXL, MER), MET and VEGF receptors. These kinases play important roles in oncogenic processes including tumor cell proliferation, metastasis, angiogenesis, drug resistance and evasion of antitumor immunity. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including colorectal cancer, kidney cancer and neuroendocrine tumors.

Zanzalintinib is an investigational agent that is not approved for any use and is the subject of ongoing clinical trials.

About CRC
CRC is the third most common cancer and the second leading cause of cancer-related deaths in the U.S.1 Approximately 154,000 new cases will be diagnosed in the U.S. with around 53,000 expected deaths from the disease in 2025.1 CRC is most frequently diagnosed among people aged 65-74 and is more common in men and in people of non-Hispanic American Indian/Alaska Native descent.2 Nearly a quarter of CRC cases are diagnosed at the metastatic stage, at which point the five-year survival rate is just 16.2%.2 The liver is the most common site for CRC metastasis. Liver metastases significantly impact survival, with a median five-year survival rate of less than 14% when treated with palliative chemotherapy.

(Press release, Exelixis, OCT 20, 2025, View Source [SID1234656814])