Raludotatug Deruxtecan for Gastrointestinal Cancer

(REJOICE-GI01 Trial)

Recruiting at 48 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine called raludotatug deruxtecan, designed to treat certain advanced gastrointestinal (GI) cancers by targeting and destroying cancer cells. The goal is to determine if this medicine can shrink or eliminate the cancer. Suitable participants have GI cancer that cannot be surgically removed and have already received treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer treatment.

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).

Is there any evidence suggesting that raludotatug deruxtecan is likely to be safe for humans?

Research has shown that raludotatug deruxtecan (R-DXd) is generally well-tolerated. In studies involving other cancers, such as ovarian cancer, about half of the patients experienced tumor shrinkage. These studies assess both the drug's effectiveness and its safety. In animal studies, R-DXd proved safe for monkeys, as it did not cause severe side effects.

This trial is in Phase 2, indicating that R-DXd has already undergone safety testing in earlier trials. Phase 2 trials focus on the treatment's effectiveness and safety, suggesting that it has demonstrated sufficient safety in humans for further testing. Participants should discuss any specific concerns or questions with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Raludotatug Deruxtecan (R-DXd) is unique because it combines an antibody with a chemotherapy drug, creating a targeted approach to treating gastrointestinal cancer. Unlike standard treatments such as chemotherapy and radiation, R-DXd specifically targets cancer cells, potentially reducing harm to healthy cells. This precision targeting could lead to fewer side effects and improved outcomes, making researchers optimistic about its potential to change the treatment landscape for gastrointestinal cancer.

What evidence suggests that raludotatug deruxtecan might be an effective treatment for gastrointestinal cancer?

Research has shown that raludotatug deruxtecan (R-DXd) holds promise for treating certain cancers. In a study involving patients with ovarian cancer unresponsive to platinum-based treatments, R-DXd shrank or eliminated tumors in about half of the cases. R-DXd is an antibody-drug conjugate (ADC), targeting cancer cells and delivering medicine directly to them to destroy the cancer. Laboratory studies have demonstrated R-DXd's strong effects against tumors in mice. These early results suggest R-DXd could effectively target and shrink tumors in gastrointestinal cancers. Participants in this trial will receive R-DXd via IV infusion to evaluate its effectiveness for gastrointestinal cancers. ^{1 2 3 5 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06864169

NCT06864169 | A Study of Raludotatug Deruxtecan (R- ... The main goal of this study is to learn if the cancer responds to treatment (gets smaller or goes away). Official Title. A Phase 2 Nonrandomized, Open-label, ...

2. onclive.com onclive.com/view/raludotatug-deruxtecan-demonstrates-promising-efficacy-safety-in-platinum-resistant-ovarian-cancer

Raludotatug Deruxtecan Demonstrates Promising Efficacy, ... R-DXd showed a 50.5% objective response rate in platinum-resistant ovarian cancer patients, with a median response time of 7.1 weeks. The ...

3. uhhospitals.org uhhospitals.org/uh-research/find-clinical-trials-and-studies/clinical-trials-search/safety-and-efficacy-of-raludotatug-deruxtecan-in-participants-with-gi-cancers-22996

Safety and Efficacy of Raludotatug Deruxtecan in ... A Phase 2 Nonrandomized, Open-label, Multisite Study to Evaluate the Safety and Efficacy of Raludotatug Deruxtecan in Participants With Gastrointestinal

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/606155

A Study of Raludotatug Deruxtecan (R-DXd) in People With ... ... Efficacy of Raludotatug Deruxtecan in Participants With Gastrointestinal Cancers. Estimated trial completion date. Jan 4, 2029. Questions about ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10911705/

Raludotatug Deruxtecan, a CDH6-Targeting Antibody–Drug ... R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys.

6. daiichisankyo.us daiichisankyo.us/press-releases/-/article/daiichi-sankyo-continues-to-transform-standards-of-care-for-patients-with-three-landmark-breast-cancer-trials-and-additional-data-across-industry-leading-adc-portfolio-at-esmo

Press Releases Raludotatug deruxtecan in participants with gastrointestinal cancers: phase 2 REJOICE-GI01 trial. M. Ueno. 1001TiP. Poster Session. Endometrial.