MK-2870 + Chemotherapy for Gastrointestinal Cancer

Recruiting at 57 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

130 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers want to learn if sacituzumab tirumotecan (MK-2870) alone or with chemotherapy can treat certain gastrointestinal (GI) cancers. The GI cancers being studied are either advanced (the cancer has spread to other parts of the body), or unresectable (the cancer cannot be removed with surgery). The goals of this study are to learn: * About the safety and how well people tolerate sacituzumab tirumotecan alone or with chemotherapy * How many people have the cancer respond (get smaller or go away) to treatment

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.

What makes the drug MK-2870 unique for gastrointestinal cancer treatment?

MK-2870, also known as Sacituzumab tirumotecan, is unique because it combines an antibody with a chemotherapy drug, allowing it to specifically target and deliver chemotherapy directly to cancer cells, potentially reducing side effects and improving effectiveness compared to traditional chemotherapy treatments. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Sacituzumab tirumotecan + Chemotherapy Experimental Treatment 5 Interventions

Participants will receive sacituzumab tirumotecan in one of two dose levels and chemotherapy by intravenous (IV) infusion, every 2 weeks. Participants will continue to receive the treatment until the cancer gets worse or they don't tolerate treatment.

Group II: Sacituzumab tirumotecan Experimental Treatment 3 Interventions

Participants will receive sacituzumab tirumotecan every 2 weeks via IV infusion. Participants will continue to receive the treatment until the cancer gets worse or they don't tolerate the 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

Findings from Research

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]

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]

References

1. Germany 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. [2021]

2. China 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. [2022]

3. United States 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. [2022]

4. England 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). [2022]

5. United States 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. [2022]