Pembrolizumab + Chemotherapy for Stomach Cancer

No longer recruiting at 210 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Pneumonitis, Active infection, Autoimmune, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding pembrolizumab, an immune-boosting drug, to chemotherapy can improve outcomes for individuals with certain types of stomach cancer (gastric or gastroesophageal junction adenocarcinoma) who have not received prior treatment. Researchers seek to discover if this combination can extend the time patients live without cancer recurrence and increase the success rate of surgery. The trial includes different treatment groups, with some receiving pembrolizumab and chemotherapy, while others receive a placebo and chemotherapy. Individuals diagnosed with localized stomach cancer that has not spread and who plan to undergo surgery might be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop these at least 14 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study combining pembrolizumab with chemotherapy did not reveal any new safety issues, meaning patients did not experience unexpected or severe side effects. Another study found that serious side effects related to the treatment occurred in about 32% of patients using pembrolizumab. Pembrolizumab is already approved for other types of cancer, suggesting it is generally safe, though all treatments can have side effects.

Chemotherapy drugs like FLOT (a mix of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) and XP/FP (combinations involving cisplatin, capecitabine, and 5-fluorouracil) are widely used. These drugs are known to have side effects, but medical care can usually manage them.

Overall, the treatments in this study have been used before, and research shows they are generally safe for most people. Always consult a doctor about any concerns or questions regarding joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments involving pembrolizumab in combination with chemotherapy for stomach cancer because they harness the power of immunotherapy to potentially enhance treatment effectiveness. Pembrolizumab is an immune checkpoint inhibitor, which means it helps the immune system recognize and attack cancer cells more effectively, a mechanism not present in traditional chemotherapy. By combining pembrolizumab with established chemotherapy regimens like FLOT (docetaxel, oxaliplatin, 5-fluorouracil, and leucovorin) or XP/FP (cisplatin with capecitabine or 5-fluorouracil), there's hope to achieve better outcomes than chemotherapy alone. This combination approach could offer a more robust treatment option by leveraging the body's immune response alongside the direct cancer-killing effects of chemotherapy.

What evidence suggests that this trial's treatments could be effective for stomach cancer?

Research has shown that adding pembrolizumab to chemotherapy can improve outcomes for stomach and gastroesophageal junction cancer. In this trial, one group of participants will receive pembrolizumab combined with FLOT chemotherapy, which has increased the chances of completely removing the tumor during surgery and may help patients live longer without cancer-related events compared to chemotherapy alone. Another group will study pembrolizumab with chemotherapy drugs like cisplatin and capecitabine or 5-fluorouracil, which has also shown promise in helping patients live longer without their cancer worsening. These findings suggest that pembrolizumab could be a valuable addition to standard chemotherapy for these cancers. ^{1 3 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Adults with untreated gastric or GEJ adenocarcinoma, planning surgery after chemotherapy, able to provide tissue samples, and in good physical condition (ECOG score 0-1). Must have a life expectancy over 6 months and adequate organ function. Women must use contraception for 180 days post-chemo or 120 days post-pembrolizumab; men also need to agree to contraception.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I agree to use birth control during and for 6 months after the study.

I agree to give tumor tissue samples before and during surgery.

Exclusion Criteria

I have had pneumonitis treated with steroids or have it now.

Has a known history of human immunodeficiency virus (HIV) infection

I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 3 cycles of pembrolizumab or placebo plus chemotherapy prior to surgery

9 weeks

4 administrations per cycle

Surgery

Participants undergo surgery following neoadjuvant treatment

1 day

Adjuvant Treatment

4 to 10 weeks post-surgery, participants receive 3 cycles of pembrolizumab or placebo plus chemotherapy, followed by pembrolizumab or placebo monotherapy

Up to 11 cycles

4 administrations per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 75 months

Extension Study (optional)

Participants may be enrolled in an extension study upon completion of the main study

What Are the Treatments Tested in This Trial?

Interventions

• 5-fluorouracil
• Capecitabine
• Cisplatin
• Docetaxel
• Leucovorin
• Oxaliplatin
• Pembrolizumab

Trial Overview The trial is testing if pembrolizumab plus chemotherapy before and/or after surgery is better than placebo plus chemotherapy for increasing the time without cancer events (EFS) and improving complete response rates at surgery in stomach/GEJ cancer patients.

How Is the Trial Designed?

Group I: Pembrolizumab+FLOT Cohort Experimental Treatment 5 Interventions

FLOT=docetaxel+oxaliplatin+5FU+leucovorin (calcium folinate). Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin (calcium folinate) 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations). Adjuvant: 4 to 10 weeks postsurgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion Day 1 Q3W PLUS docetaxel 50 mg/m\^2, oxaliplatin 85 mg/m\^2, 5FU 2600 mg/m\^2, and leucovorin 200 mg/m\^2 Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations), followed by pembrolizumab monotherapy 200 mg via IV infusion on Day 1 Q3W for up to 11 additional cycles.

Group II: Pembrolizumab + XP/FP Experimental Treatment 4 Interventions

XP=cisplatin+capecitabine and FP=cisplatin+5-fluorouracil. Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets twice each day (BID) on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2 continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of pembrolizumab 200 mg IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by pembrolizumab monotherapy 200 mg IV infusion on Day 1 Q3W for up to 11 additional cycles.

Group III: Placebo+FLOT Cohort Placebo Group 5 Interventions

Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations). Adjuvant: 4 to 10 weeks postsurgery, participants receive 3 cycles of placebo via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations), followed by placebo monotherapy via IV infusion on Day 1 Q3W for up to 11 additional cycles.

Group IV: Placebo + XP/FP Placebo Group 4 Interventions

Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of placebo via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by placebo monotherapy via IV infusion on Day 1 Q3W for up to 11 additional cycles.

5-fluorouracil is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in European Union as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead 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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40829093/

Final Analysis of the Randomized, Phase III KEYNOTE-585 ... Pembrolizumab plus chemotherapy continued to show improved outcomes in pathCR and a trend toward longer EFS versus placebo in the main and main plus FLOT ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.247

Pembrolizumab plus FLOT vs FLOT as neoadjuvant and ... ... FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) Q2W for 4 cycles. After surgery, pts received adjuvant pembro or pbo Q3W for 3 cycles + FLOT ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11811557/

KEYNOTE-585: disappointing results for perioperative ... Despite the lack of success with pembrolizumab added to perioperative chemotherapy in gastric cancer, KEYNOTE-585 is a landmark accomplishment ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT435104

Interim analysis of the phase 3 KEYNOTE-585 study. Pembrolizumab plus FLOT vs FLOT as neoadjuvant and adjuvant therapy in locally advanced gastric and gastroesophageal junction cancer: Interim analysis of the ...

5. nature.com nature.com/articles/s41591-025-03979-y

Perioperative pembrolizumab, trastuzumab and FLOT in ... Treatment-related SAEs were attributed to pembrolizumab in 32.3% of patients, trastuzumab in 22.6%, oxaliplatin in 41.9%, 5-FU in 48.4%, folinic ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06411171

Safety and Efficacy of Pembrolizumab in Combination With ... Studies have shown that PD-L1 is highly expressed in tumor cells and immune cells in gastric cancer and gastroesophageal junction cancer and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12572790/

Neoadjuvant FLOT versus SOX chemotherapy in locally ... Both FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) and SOX (S-1 plus oxaliplatin) regimens are widely used for neoadjuvant ...