S095029 + Pembrolizumab for Stomach Cancer
Recruiting in Palo Alto (17 mi)
+41 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Servier Bio-Innovation LLC
Must not be taking: Checkpoint inhibitors
Disqualifiers: Multiple prior treatments, Recent surgery, others
No Placebo Group
Breakthrough Therapy
Approved in 2 Jurisdictions
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.
12345Is 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.
56789What 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.
1561011Eligibility 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.
+2 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: S095029 and pembrolizumabExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MD Anderson Cancer CenterHouston, TX
Ocala Oncology Center PlOcala, FL
Investigative Clinical Research of Indiana, LlcNoblesville, IN
Mount Sinai HospitalToronto, Canada
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Who Is Running the Clinical Trial?
Servier Bio-Innovation LLCLead Sponsor
Institut de Recherches Internationales ServierCollaborator
Merck Sharp & Dohme LLCIndustry Sponsor
References
Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. [2022]Pembrolizumab plus chemotherapy significantly improved survival outcomes versus placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC in the randomized, double-blind, phase 3 KEYNOTE-407 study. We present the results of Chinese patients enrolled in the KEYNOTE-407 global and China extension studies.
FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1. [2021]On September 22, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab (Keytruda, Merck & Co., Inc., Whitehouse Station, NJ) for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after two or more systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy, and whose tumors express programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test. Approval was based on demonstration of durable overall response rate (ORR) in a multicenter, open-label, multicohort trial (KEYNOTE-059/Cohort 1) that enrolled 259 patients with locally advanced or metastatic gastric or GEJ adenocarcinoma. Among the 55% (n = 143) of patients whose tumors expressed PD-L1 based on a combined positive score ≥1 and either were microsatellite stable or had undetermined microsatellite instability or mismatch repair status, the confirmed ORR as determined by blinded independent central review was 13.3% (95% CI, 8.2-20.0); 1.4% had complete responses. Response durations ranged from 2.8+ to 19.4+ months; 11 patients (58%) had response durations of 6 months or longer, and 5 patients (26%) had response durations of 12 months or longer. The most common (≥20%) adverse reactions of pembrolizumab observed in KEYNOTE-059/Cohort 1 were fatigue, decreased appetite, nausea, and constipation. The most frequent (≥2%) serious adverse drug reactions were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. Pembrolizumab was approved concurrently with the PD-L1 immunohistochemistry 22C3 pharmDx test (Dako, Agilent, Santa Clara, CA) for selection of patients with gastric cancer for treatment with pembrolizumab based on PD-L1 tumor expression. IMPLICATIONS FOR PRACTICE: This report presents key information on the basis for Food and Drug Administration approval of pembrolizumab for the treatment of patients with locally advanced or metastatic gastric or GEJ adenocarcinoma whose tumors express PD-L1. The report discusses the basis for limiting the indication to patients with PD-L1-expressing tumors and the basis for recommending that PD-L1 status be assessed using a fresh tumor specimen if PD-L1 expression is not detected in an archival gastric or GEJ cancer specimen.
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]KEYNOTE-063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second-line therapy in Asian patients with advanced programmed death ligand 1 (PD-L1)-positive (combined positive score ≥1) gastric/gastroesophageal junction (GEJ) cancer.
Determinants of Response and Intrinsic Resistance to PD-1 Blockade in Microsatellite Instability-High Gastric Cancer. [2022]Sequence alterations in microsatellites and an elevated mutational burden are observed in 20% of gastric cancers and associated with clinical response to anti-PD-1 antibodies. However, 50% of microsatellite instability-high (MSI-H) cancers are intrinsically resistant to PD-1 therapies. We conducted a phase II trial of pembrolizumab in patients with advanced MSI-H gastric cancer and included serial and multi-region tissue samples in addition to serial peripheral blood analyses. The number of whole-exome sequencing (WES)-derived nonsynonymous mutations correlated with antitumor activity and prolonged progression-free survival (PFS). Coupling WES to single-cell RNA sequencing, we identified dynamic tumor evolution with greater on-treatment collapse of mutational architecture in responders. Diverse T-cell receptor repertoire was associated with longer PFS to pembrolizumab. In addition, an increase in PD-1+ CD8+ T cells correlated with durable clinical benefit. Our findings highlight the genomic, immunologic, and clinical outcome heterogeneity within MSI-H gastric cancer and may inform development of strategies to enhance responsiveness. SIGNIFICANCE: This study highlights response heterogeneity within MSI-H gastric cancer treated with pembrolizumab monotherapy and underscores the potential for extended baseline and early on-treatment biomarker analyses to identify responders. The observed markers of intrinsic resistance have implications for patient stratification to inform novel combinations among patients with intrinsically resistant features.See related commentary by Fontana and Smyth, p. 2126.This article is highlighted in the In This Issue feature, p. 2113.
A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). [2022]Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy.
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.
Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC).
A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). [2020]Pembrolizumab shows robust antitumor activity and favorable safety in metastatic melanoma. KEYNOTE-151 evaluated pembrolizumab in Chinese patients, who have more aggressive melanoma subtypes than other populations.
Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial). [2021]This is a phase I/II trial to assess the efficacy and safety of napabucasin plus pembrolizumab for metastatic colorectal cancer (mCRC).
[Microsatellite Instability in Gastric Cancer]. [2020]Pembrolizumab and nivolumab are anti-programmed death receptor-1(PD-1)antibodies. The use of pembrolizumab for unresectable or metastatic cancer with microsatellite instability-high(MSI-High)has been recently approved. However, there were few clinical reports on MSI in gastric cancer.
Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data. [2022]Pembrolizumab is a programmed death-ligand 1 inhibitor that was initially indicated for monotherapy in patients with advanced lung cancer. The Japanese Lung Cancer Society conducted an observational study on pembrolizumab using confirmative data obtained through postmarketing all-case surveillance (PMACS), which was performed by a pharmaceutical company under the Japanese law in 2017.