MK-2870 + Chemotherapy for Gastrointestinal Cancer

Recruiting at 73 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Severe eye disease, Pneumonitis, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 53 months

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called sacituzumab tirumotecan (also known as MK-2870) to determine its effectiveness in treating certain advanced gastrointestinal (GI) cancers. Researchers are testing it alone and in combination with other treatments to evaluate its ability to shrink or eliminate tumors. The study focuses on safety and patient tolerance. It suits patients with advanced or widespread GI cancers, such as pancreatic or biliary tract cancer, who have already tried other treatments. As a Phase 1, Phase 2 trial, it allows patients to be among the first to receive this new treatment while assessing its effectiveness in a smaller group.

Will I have to stop taking my current medications?

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

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

Previous studies have shown that sacituzumab tirumotecan has a manageable safety profile, with most side effects not being severe. For instance, one study reported common side effects such as anemia (low red blood cells) in 64.6% of patients, with 20.8% experiencing it more severely. Importantly, no treatment-related deaths have been reported.

When combined with cisplatin and pembrolizumab, researchers are still gathering safety data on sacituzumab tirumotecan. These trials are in the early stages, focusing on the treatment's safety and the body's response. Early trials involve a small number of participants to identify any serious side effects before progressing to larger studies.

Overall, sacituzumab tirumotecan, both alone and in combination with other drugs, appears well-tolerated based on available data. Participants should be aware of possible side effects and discuss any concerns with the research team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sacituzumab tirumotecan for gastrointestinal cancer because it offers a novel approach by combining an antibody-drug conjugate with chemotherapy. Unlike standard treatments like fluorouracil or oxaliplatin, sacituzumab tirumotecan delivers a targeted chemotherapy directly to cancer cells, potentially reducing side effects and increasing effectiveness. In one treatment arm, it's paired with cisplatin and pembrolizumab, aiming to enhance its immune response and cytotoxic effects. This combination could provide a more comprehensive attack on cancer cells compared to traditional therapies.

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

Research has shown that sacituzumab tirumotecan may help treat various types of gastrointestinal cancers. In one study, 70.7% of patients experienced tumor shrinkage or disappearance, indicating a positive outcome. The treatment also controlled the disease in 92.7% of patients, effectively managing the cancer. In this trial, participants will receive sacituzumab tirumotecan either alone or with chemotherapy, including cisplatin and pembrolizumab. When combined with cisplatin and pembrolizumab, sacituzumab tirumotecan was generally safe and showed promising results against tumors. These early findings suggest it could be effective for patients with advanced or difficult-to-remove GI cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced or inoperable gastrointestinal cancers, including colorectal, biliary tract, and pancreatic cancers. Participants must have had prior cancer therapy and recovered from its side effects.

Inclusion Criteria

My colorectal cancer cannot be removed by surgery or has spread.

My cancer is advanced pancreatic cancer.

My biliary tract cancer cannot be removed by surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab tirumotecan alone or with chemotherapy every 2 weeks via IV infusion until disease progression or unacceptable toxicity

Up to approximately 53 months

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil (5-FU)
• Rescue medication
• Sacituzumab tirumotecan
• Supportive care measures

Trial Overview The study tests sacituzumab tirumotecan (MK-2870) alone or combined with chemotherapy (5-FU and leucovorin). It aims to assess the treatment's safety, tolerability, and effectiveness in shrinking or eliminating tumors.

How Is the Trial Designed?

Group I: Sacituzumab tirumotecan + Cisplatin + Pembrolizumab Experimental Treatment 3 Interventions

Participants will receive sacituzumab tirumotecan in one of two dose levels on Day 1 and Day 8 of every 3-week cycle until the cancer gets worse or they don't tolerate treatment, cisplatin on Day 1 and Day 8 of each 3-week cycle for up to 8 cycles (up to approximately 6 months), and pembrolizumab on Day 1 of each 3-week cycle for up to approximately 2 years.

Group II: Sacituzumab tirumotecan + Chemotherapy Experimental Treatment 5 Interventions

Participants will receive sacituzumab tirumotecan in one of two dose levels and chemotherapy every 2 weeks (Day 1 and Day 15 of every 4-week cycle). Participants will continue to receive the treatment until the cancer gets worse or they don't tolerate treatment.

Group III: Sacituzumab tirumotecan Experimental Treatment 3 Interventions

Participants will receive sacituzumab tirumotecan every 2 weeks (Day 1 and Day 15 of every 4-week cycle). Participants will continue to receive the treatment until the cancer gets worse or they don't tolerate treatment.

Sacituzumab tirumotecan is already approved in China for the following indications:

Approved in China as Sacituzumab tirumotecan for:

• Unresectable locally advanced or metastatic triple-negative breast cancer

Who Is Running the Clinical Trial?

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

Published Research Related to This Trial

The addition of tivantinib to the standard treatment of cetuximab and irinotecan did not significantly improve progression-free survival (PFS) in patients with KRAS wild-type metastatic colorectal cancer, with PFS of 8.3 months for tivantinib versus 7.3 months for placebo.

While the combination was well tolerated, with common side effects including neutropenia and diarrhea, there were indications that tivantinib might be more effective in specific subgroups of patients, such as those with MET-High tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled, phase 1/2 study of tivantinib (ARQ 197) in combination with irinotecan and cetuximab in patients with metastatic colorectal cancer with wild-type KRAS who have received first-line systemic therapy. Eng, C., Bessudo, A., Hart, LL., et al.[2022]

In a study involving 20 Japanese patients with advanced colorectal cancer, the combination of MK-0646 with cetuximab and irinotecan was found to be well tolerated, with only one patient experiencing a dose-limiting toxicity (grade 3 hyperglycemia).

The combination therapy increased the exposure of MK-0646 by 25% without affecting the pharmacokinetics of cetuximab and irinotecan, although it did reduce the levels of SN-38, the active metabolite of irinotecan, indicating minimal drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Doi, T., Muro, K., Yoshino, T., et al.[2021]

In a study of 56 patients with metastatic gastric or gastroesophageal junction adenocarcinoma, the combination of ramucirumab with FOLFIRI resulted in a median overall survival of 8.3 months, which was significantly better than the 4.4 months observed with ramucirumab and paclitaxel.

The treatment was generally safe, with manageable adverse effects, primarily neutropenia and polyneuropathy, indicating that ramucirumab combined with FOLFIRI could be a promising option for patients who have already undergone platinum and taxane-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab plus paclitaxel or FOLFIRI in platinum-refractory advanced or metastatic gastric or gastroesophageal junction adenocarcinoma-experience at two centres. Vogl, UM., Vormittag, L., Winkler, T., et al.[2022]

In a study of 182 patients with metastatic colorectal cancer, the combination of FOLFIRI with either panitumumab or bevacizumab showed similar efficacy in terms of progression-free survival (PFS) and overall survival (OS), indicating that both treatments are viable options after disease progression during previous chemotherapy.

While both treatments had comparable effectiveness, panitumumab was associated with more skin disorders and gastrointestinal side effects, while bevacizumab led to a higher incidence of neutropenia, highlighting the importance of considering side effects when choosing a treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SPIRITT: A Randomized, Multicenter, Phase II Study of Panitumumab with FOLFIRI and Bevacizumab with FOLFIRI as Second-Line Treatment in Patients with Unresectable Wild Type KRAS Metastatic Colorectal Cancer. Hecht, JR., Cohn, A., Dakhil, S., et al.[2022]

In a phase II study involving 37 patients with wild-type KRAS, HRAS, NRAS, and BRAF unresectable metastatic colorectal cancer, the combination of panitumumab with a modified FOLFOXIRI regimen resulted in a high overall response rate of 89%, with 43% of patients undergoing successful secondary surgery for metastases.

The study demonstrated that while the treatment was effective, it also led to significant adverse events, including neutropenia and diarrhoea, prompting a reduction in fluorouracil and irinotecan doses to enhance safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI in combination with panitumumab as first-line treatment in quadruple wild-type (KRAS, NRAS, HRAS, BRAF) metastatic colorectal cancer patients: a phase II trial by the Gruppo Oncologico Nord Ovest (GONO). Fornaro, L., Lonardi, S., Masi, G., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/show/NCT06428409

NCT06428409 | A Clinical Study of MK-2870 Alone or With ... The goals of this study are to learn: About the safety of sacituzumab tirumotecan alone or with other treatments and if people tolerate it; How ...

2. cancernetwork.com cancernetwork.com/view/sacituzumab-tirumotecan-shows-early-efficacy-in-gastric-gej-cancers

Sacituzumab Tirumotecan Shows Early Efficacy in Gastric/ ... At a median follow-up of 14.2 months, the objective response rate (ORR) with sacituzumab tirumotecan was 22.0% (n = 9/48), which included 7 ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT493500

Sacituzumab tirumotecan (sac-TMT) as first-line treatment ... The median follow-up was 18.6 mo. The objective response rate (ORR) was 70.7% (29/41, 3 unconfirmed PR) and the disease control rate (DCR) was 92.7%. Median ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12142944/

Results of a phase 1/2 study of sacituzumab tirumotecan in ... Sac-TMT demonstrated manageable safety profile in patients with unresectable locally advanced/metastatic solid tumors and promising antitumor ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.796

Report from the phase 1/2 MK-2870-001 study. No treatment-related deaths were reported by safety data cutoff (May 21, 2024). Efficacy outcomes are shown in the Table. Conclusions: sac-TMT ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06356311

A Study to Evaluate Sacituzumab Tirumotecan (MK-2870) ... This study will compare how safe and effective sacituzumab tirumotecan is versus the treatment of physician's choice (TPC) in participants with ...