Raludotatug Deruxtecan for Gastrointestinal Cancer

(REJOICE-GI01 Trial)

Recruiting at 22 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretroviral therapy

Disqualifiers: ILD, Cardiovascular disease, CNS metastases, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 15 months

160 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have HIV, you must have it well controlled on antiretroviral therapy (ART).

What data supports the effectiveness of the drug Raludotatug Deruxtecan (R-DXd) for gastrointestinal cancer?

Raltitrexed, a component of R-DXd, has shown effectiveness in treating various gastrointestinal cancers, including colorectal and pancreatic cancers, as demonstrated in multiple studies. It has been effective both as a single agent and in combination with other drugs, suggesting potential benefits for gastrointestinal cancer treatment. ^{1 2 3 4 5}

Is Raludotatug Deruxtecan safe for humans?

Trastuzumab deruxtecan, a similar treatment, has been studied for safety in various cancers, showing manageable side effects but with some risk of serious lung issues in about 10% of patients. ^{6 7 8 9 10}

What makes the drug Raludotatug Deruxtecan unique for gastrointestinal cancer?

Raludotatug Deruxtecan (R-DXd) is unique because it combines a targeted therapy approach with a chemotherapy agent, potentially offering a novel mechanism of action compared to traditional treatments. While similar drugs like raltitrexed target specific enzymes in cancer cells, R-DXd may provide a more direct delivery of chemotherapy to cancer cells, which could improve effectiveness and reduce side effects. ^{1 4 11 12 13}

What is the purpose of this trial?

Researchers are looking for new ways to treat certain types of advanced gastrointestinal (GI) cancers. The study medicine raludotatug deruxtecan (also called MK-5909, R-DXd, or DS-6000a) is a type of medicine called an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The main goal of this study is to learn if the cancer responds to treatment (gets smaller or goes away).

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for people with advanced gastrointestinal cancers who have a life expectancy of at least 3 months. It's open to those with certain types of cancer like pancreatic, esophageal, biliary tract, colorectal, gastroesophageal junction, and gastric adenocarcinomas. Participants must have had previous cancer therapy and if HIV-positive, their HIV must be well-controlled.

Inclusion Criteria

My doctor expects me to live at least 3 more months.

My pancreatic cancer cannot be removed by surgery.

I have esophageal adenocarcinoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Raludotatug Deruxtecan (R-DXd) via IV infusion to evaluate the cancer response

Approximately 15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 49 months

Treatment Details

Interventions

• Raludotatug Deruxtecan (R-DXd)

Trial Overview The study tests Raludotatug Deruxtecan (R-DXd), an antibody-drug conjugate designed to target and destroy cancer cells in patients with specific advanced gastrointestinal cancers. The main goal is to see if the treatment reduces or eliminates the cancer.

Participant Groups

Group I: Raludotatug Deruxtecan (R-DXd) Experimental Treatment 1 Intervention

R-DXd will be administered via IV infusion.

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

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Findings from Research

Paclitaxel demonstrated significant effectiveness against esophageal cancer in a phase II trial, indicating its potential as a treatment option for this type of cancer.

Irinotecan has proven to be effective as a single-agent treatment for both gastric and colorectal cancers, while docetaxel showed notable activity in advanced gastric cancer and a 29% response rate in pancreatic cancer, highlighting its versatility in treating various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New systemic drugs in the treatment of gastrointestinal cancer. Ogawa, M.[2019]

In a phase II trial involving 48 patients with untreated advanced colorectal cancer, the combination of irinotecan and raltitrexed showed an overall response rate of 27%, with a median duration of response of 10 months.

Despite its activity, the treatment was associated with significant side effects, including grade III-IV diarrhea and neutropenia, leading to a dose reduction and highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer. Chiara, S., Nobile, MT., Tomasello, L., et al.[2018]

In a phase II study involving 46 patients with advanced pancreatic and biliary carcinomas, raltitrexed was generally well tolerated, with a median survival of 4.6 months and a 1-year survival rate of 21.8%.

Only a small percentage of patients experienced improvements in quality of life (7.0%) and clinical benefit response (15.6%), indicating limited efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of raltitrexed (Tomudex) in advanced pancreatic and biliary carcinoma. François, E., Hebbar, M., Bennouna, J., et al.[2014]

Trastuzumab deruxtecan (T-DXd) is a promising HER2-targeted therapy that has shown significant anti-tumor activity in heavily pre-treated patients with HER2-positive breast and gastric cancers, and preliminary data suggest it may also be effective in HER2-positive non-small cell lung cancer (NSCLC) and colorectal cancer.

While T-DXd has an acceptable safety profile, there are concerns about serious treatment-emergent adverse events, highlighting the need for careful monitoring in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors. Indini, A., Rijavec, E., Grossi, F.[2021]

Trastuzumab deruxtecan (T-DXd) was evaluated for safety in 1457 patients across 8 clinical trials, revealing that gastrointestinal disorders and blood-related issues were the most common adverse events, with neutropenia being the most severe (21.4% incidence).

The study highlighted significant concerns regarding interstitial lung disease (10.9% incidence) and decreased left ventricular ejection fraction (1.2% incidence), suggesting that while T-DXd is generally well tolerated, these specific side effects require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. Guo, Z., Ding, Y., Wang, M., et al.[2023]

Trastuzumab deruxtecan (T-DXd) demonstrated clinical activity in patients with HER2-low gastric or gastroesophageal junction adenocarcinoma, showing a confirmed objective response rate of 26.3% in cohort 1 and 9.5% in cohort 2, with many patients experiencing reduced tumor size.

The treatment was generally well-tolerated, with no drug-related deaths reported, although some patients experienced significant adverse events like anemia and decreased neutrophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. Yamaguchi, K., Bang, YJ., Iwasa, S., et al.[2023]

In a study involving 24 patients with recurrent head and neck cancer, raltitrexed was administered as a single agent but did not result in any complete or partial responses, indicating limited efficacy for this specific cancer type.

Despite the lack of significant anti-tumor responses, raltitrexed was generally well tolerated, with minimal toxicity reported, suggesting it may be safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open label, multi-centre phase II study of raltitrexed ('Tomudex') in patients with inoperable squamous-cell carcinoma of head and neck. Clarke, SJ., Zalcberg, J., Olver, I., et al.[2020]

Raltitrexed is an effective treatment for advanced colorectal cancer, showing similar efficacy to the standard combination therapy of 5-fluorouracil and leucovorin, based on Phase III studies.

Patients treated with raltitrexed experienced fewer severe side effects compared to those on 5-FU + LV, making it a better-tolerated alternative for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltitrexed (Tomudex). Van Cutsem, E.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

A dose-finding study of raltitrexed (tomudex) with cisplatin and epirubicin in advanced gastro-oesophageal adenocarcinoma. [2018]

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

New systemic drugs in the treatment of gastrointestinal cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Future developments with 'Tomudex' (raltitrexed). [2019]

4. Greece pubmed.ncbi.nlm.nih.gov

Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A phase II trial of raltitrexed (Tomudex) in advanced pancreatic and biliary carcinoma. [2014]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors. [2021]

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

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. [2023]

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

Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for the treatment of patients with HER2-positive gastric cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan Dosing in Human Epidermal Growth Factor Receptor 2-Positive Gastric Cancer: Population Pharmacokinetic Modeling and Exposure-Response Analysis. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Open label, multi-centre phase II study of raltitrexed ('Tomudex') in patients with inoperable squamous-cell carcinoma of head and neck. [2020]

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

Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group. [2017]

13. England pubmed.ncbi.nlm.nih.gov

Raltitrexed (Tomudex). [2019]