S095029 + Pembrolizumab for Stomach Cancer

Recruiting at 51 trial locations

Overseen By Institut de Recherches Internationales Servier, Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Servier Bio-Innovation LLC

Must not be taking: Checkpoint inhibitors

Disqualifiers: Multiple prior treatments, Recent surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will investigate the safety, tolerability, and antitumor activity of S095029 (anti-NKG2A antibody) in combination with pembrolizumab in in microsatellite instability-high/Defective mismatch repair (MSI-H/dMMR) locally advanced unresectable or metastatic gastric /GEJ adenocarcinomas.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must not have received any systemic anti-cancer therapy within 4 weeks before starting the study treatment.

What data supports the effectiveness of the drug S095029 + Pembrolizumab for stomach cancer?

Pembrolizumab has been approved by the FDA for treating certain types of advanced stomach cancer, showing a response in some patients whose tumors express a specific protein called PD-L1. This suggests that pembrolizumab can be effective for stomach cancer, especially when combined with other treatments. ^{1 2 3 4 5}

Is pembrolizumab generally safe for humans?

Pembrolizumab has been shown to have very little toxicity in a large study with melanoma patients, indicating it is generally safe for humans. ^{5 6 7 8 9}

What makes the drug S095029 + Pembrolizumab unique for stomach cancer?

S095029 (Libtayo, cemiplimab-rwlc) combined with pembrolizumab is unique because it involves two drugs that target the PD-1 pathway, which helps the immune system recognize and attack cancer cells. This combination is being explored for stomach cancer, where there are limited standard treatment options, especially for advanced stages. ^{1 5 6 10 11}

Eligibility Criteria

This trial is for adults with advanced stomach or gastroesophageal junction cancer that can't be removed by surgery. Their tumors must show a high level of microsatellite instability (MSI-H) or defective mismatch repair (dMMR), which are specific genetic features.

Inclusion Criteria

My cancer is in the stomach or where the stomach meets the esophagus and cannot be surgically removed.

My tumor is MSI-H or dMMR as per the tests.

Exclusion Criteria

I finished radiotherapy less than 2 weeks ago.

I have been treated with immunotherapy drugs before.

I have had more than one treatment for my advanced or metastatic cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in (Phase 1b)

Participants receive S095029 in combination with pembrolizumab to identify the recommended Phase 2 dose (RP2D)

Approximately 3 months

Regular visits for dose evaluation and safety monitoring

Expansion (Phase 2)

Participants receive the recommended Phase 2 dose (RP2D) of S095029 with pembrolizumab to evaluate anti-tumor activity and safety

Approximately 2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose

Treatment Details

Interventions

• S095029

Trial Overview The study tests S095029, an experimental drug targeting immune cells, combined with pembrolizumab, an approved immunotherapy. It aims to assess safety and effectiveness in shrinking or controlling the growth of these cancers.

Participant Groups

Group I: S095029 and pembrolizumab Experimental Treatment 2 Interventions

Participants diagnosed with gastric cancer (GC) or gastroesophageal junction cancer (GEJ), not previously treated with checkpoint inhibitors (CPIs) may first be enrolled into a Phase 1b safety lead-in part which will be used to identify the recommended Phase 2 dose (RP2D) of S095029 in combination with pembrolizumab. During the Phase 2 part, participants will receive the recommended Phase 2 dose (RP2D) of S095029, along with pembrolizumab.

S095029 is already approved in United States, European Union for the following indications:

Approved in United States as Libtayo for:

• Advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression and no EGFR, ALK, or ROS1 aberrations
• Advanced NSCLC in combination with platinum-based chemotherapy

Approved in European Union as Libtayo for:

• Not specified in the provided sources, but generally approved for similar indications as in the US

Who Is Running the Clinical Trial?

Servier Bio-Innovation LLC

Lead Sponsor

Trials

9

Recruited

670+

Institut de Recherches Internationales Servier

Collaborator

Trials

91

Recruited

67,100+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a study involving 125 Chinese patients with metastatic squamous non-small cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) compared to placebo plus chemotherapy, with hazard ratios of 0.44 and 0.35, respectively.

Patients receiving pembrolizumab-chemotherapy also reported better quality of life and had a longer time before experiencing worsening symptoms like cough and chest pain, indicating that this treatment not only extends survival but also maintains health-related quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. Cheng, Y., Zhang, L., Hu, J., et al.[2022]

Pembrolizumab (Keytruda) received FDA accelerated approval for treating recurrent gastric or gastroesophageal junction adenocarcinoma in patients whose tumors express PD-L1, based on a multicenter trial involving 259 patients, showing a 13.3% overall response rate.

The treatment was associated with common side effects like fatigue and decreased appetite, and serious adverse reactions included pneumonia and pulmonary embolism, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1. Fashoyin-Aje, L., Donoghue, M., Chen, H., et al.[2021]

In a phase 3 study involving 94 Asian patients with advanced PD-L1-positive gastric/GEJ cancer, pembrolizumab showed similar overall survival (OS) to paclitaxel, with a median OS of 8 months for both treatments, indicating comparable efficacy.

Pembrolizumab had a significantly better safety profile, with only 60% of patients experiencing any-grade treatment-related adverse events compared to 96% for paclitaxel, and fewer severe (grades 3 to 5) events (11% vs. 64%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Chung, HC., Kang, YK., Chen, Z., et al.[2022]

In a phase II trial of pembrolizumab for advanced MSI-H gastric cancer, the number of nonsynonymous mutations identified through whole-exome sequencing was linked to better antitumor activity and longer progression-free survival, indicating that genetic profiling can help predict treatment outcomes.

The study found that an increase in PD-1+ CD8+ T cells was associated with durable clinical benefits, highlighting the importance of immune response in determining the effectiveness of PD-1 therapies in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of Response and Intrinsic Resistance to PD-1 Blockade in Microsatellite Instability-High Gastric Cancer. Kwon, M., An, M., Klempner, SJ., et al.[2022]

Pembrolizumab (P) can be safely combined with various chemotherapy agents, including gemcitabine and liposomal doxorubicin, in patients with advanced solid tumors, as shown in a phase Ib trial involving 49 patients.

The combination treatment resulted in eight partial responses across different tumor types, indicating potential efficacy, but further studies are needed to confirm if the response duration is better than chemotherapy or immunotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Weiss, GJ., Waypa, J., Blaydorn, L., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

In a phase I/II trial involving 55 patients with metastatic colorectal cancer, the combination of napabucasin and pembrolizumab showed promising antitumor activity, particularly in patients with microsatellite instability high (MSI-H) tumors, achieving an immune-related objective response rate (irORR) of 50%.

The treatment was generally well-tolerated, with no dose-limiting toxicities observed at the recommended phase 2 dose of napabucasin (480 mg), although the overall efficacy did not meet the primary endpoint, highlighting the need for further investigation into biomarkers that may influence treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial). Kawazoe, A., Kuboki, Y., Shinozaki, E., et al.[2021]

In a study of 37 patients with unresectable gastric cancer, 8.1% were found to have microsatellite instability-high (MSI-High), which may influence treatment response.

Among 11 patients treated with nivolumab, 75% of those who achieved a partial response were MSI-High, suggesting that anti-PD-1 therapy could be particularly effective for this subgroup of gastric cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Microsatellite Instability in Gastric Cancer]. Choda, Y., Kubota, T., Ishida, M., et al.[2020]

In a multicenter observational study involving 300 patients with non-small cell lung cancer (NSCLC), pembrolizumab demonstrated a median overall survival of 558 days and a progression-free survival of 188 days, indicating its efficacy in real-world settings.

The study confirmed that factors such as performance status and PD-L1 expression significantly influenced overall survival, while the toxicity profile of pembrolizumab remained consistent with previous reports, suggesting it is a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data. Terai, H., Soejima, K., Shimokawa, A., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. [2022]

2. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Determinants of Response and Intrinsic Resistance to PD-1 Blockade in Microsatellite Instability-High Gastric Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial). [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

[Microsatellite Instability in Gastric Cancer]. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data. [2022]