T-DXd Combinations for Stomach Cancer

(DG-03 Trial)

Recruiting in Palo Alto (17 mi)

+53 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AstraZeneca

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

DESTINY-Gastric03 will investigate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of trastuzumab deruxtecan (T-DXd) alone or in combination with chemotherapy and/or immunotherapy in HER2-expressing advanced/metastatic gastric/gastroesophageal junction (GEJ) and esophageal adenocarcinoma patients. Study hypotheses: Combination of T-DXd with cytotoxic chemotherapy and/or immunotherapy administered to subjects at the recommended phase 2 dose will show manageable safety and tolerability and preliminary anti-tumor efficacy so as to permit further clinical testing. T-DXd in combination with cytotoxic chemotherapy or immune checkpoint inhibitor administered to HER2-expressing gastric, GEJ and esophageal cancer patients who have not received prior treatment for advanced/metastatic disease will show preliminary evidence of anti-tumour activity and the potential to become a therapeutic option for this patient population.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug T-DXd Combinations for Stomach Cancer?

Research shows that combinations of drugs like cisplatin and 5-fluorouracil (5-FU) are effective in treating advanced gastric cancer, and T-DXd has shown strong results in treating HER2-positive breast cancer, suggesting potential benefits for similar conditions.

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Is the T-DXd combination treatment generally safe for humans?

Studies involving combinations of drugs like cisplatin, fluorouracil, and capecitabine have shown that while they can be effective, they often come with significant side effects, such as neutropenia (a low level of white blood cells that can increase infection risk). Safety profiles vary, and it's important to discuss potential risks with your healthcare provider.

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What makes the T-DXd drug combination unique for stomach cancer?

The T-DXd drug combination for stomach cancer is unique because it includes Trastuzumab deruxtecan, a targeted therapy that delivers chemotherapy directly to cancer cells, potentially increasing effectiveness while reducing side effects compared to traditional chemotherapy. This approach is different from standard treatments that often involve more generalized chemotherapy drugs.

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Eligibility Criteria

This trial is for adults with advanced HER2-expressing stomach, GEJ, or esophageal cancer. Participants must have progressed after a trastuzumab regimen (Part 1) or be untreated for metastatic disease (Part 2), and have measurable disease. They need proper organ function and agree to contraception if of reproductive potential. Exclusions include active infections like HIV/HBV/HCV, uncontrolled illnesses, CNS metastases, lung issues like ILD/pneumonitis, and problematic fluid accumulation.

Inclusion Criteria

My cancer has spread and cannot be removed with surgery.

I am at least 18 years old.

My heart, kidneys, and liver are functioning well.

Exclusion Criteria

I do not have a history of significant immune system diseases or known HIV, hepatitis B, or C.

I have or might have a lung condition not caused by infection.

I do not have any severe lung-related illnesses.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive T-DXd alone or in combination with chemotherapy and/or immunotherapy

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

DESTINY-Gastric03 tests the safety and effectiveness of T-DXd alone or combined with chemotherapy/immunotherapy in advanced gastric cancers expressing HER2. The study aims to find tolerable doses that show anti-tumor activity as a potential new treatment option for patients who haven't received prior therapy for their metastatic disease.

Group I: Arm 4B Experimental Treatment 4 Interventions

T-DXd, Rilvegostomig and 5-FU or capecitabine

Group II: Arm 4A Experimental Treatment 4 Interventions

T-DXd, Rilvegostomig and 5-FU or capecitabine

Group III: Arm 3B Experimental Treatment 4 Interventions

T-DXd, Volrustomig and 5-FU or capecitabine

Group IV: Arm 3A Experimental Treatment 4 Interventions

T-DXd, Volrustomig and 5-FU or capecitabine

Group V: Arm 2F Experimental Treatment 4 Interventions

T-DXd, pembrolizumab and 5-FU or capecitabine

Group VI: Arm 2E Experimental Treatment 2 Interventions

T-DXd and pembrolizumab

Group VII: Arm 2D Experimental Treatment 4 Interventions

T-DXd, pembrolizumab and 5-FU or capecitabine

Group VIII: Arm 2C Experimental Treatment 4 Interventions

T-DXd, 5-FU or capecitabine

Group IX: Arm 2B Experimental Treatment 1 Intervention

T-DXd monotherapy

Group X: Arm 1E(b) Experimental Treatment 3 Interventions

T-DXd, capecitabine, and durvalumab

Group XI: Arm 1E(a) Experimental Treatment 3 Interventions

T-DXd, 5-FU, and durvalumab

Group XII: Arm 1D(b) Experimental Treatment 3 Interventions

T-DXd, capecitabine, and oxaliplatin

Group XIII: Arm 1C Experimental Treatment 2 Interventions

T-DXd and durvalumab

Group XIV: Arm 1B Experimental Treatment 2 Interventions

T-DXd and capecitabine

Group XV: Arm 1A Experimental Treatment 2 Interventions

T-DXd and 5-fluorouracil (5-FU)

Group XVI: Arm 2A Active Control 5 Interventions

Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin

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

🇪🇺 Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

🇺🇸 Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

🇨🇦 Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

🇯🇵 Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Site Quebec, Canada

Research Site Baltimore, MD

Research Site New York, NY

Research Site Houston, TX

More Trial Locations

Who Is Running the Clinical Trial?

AstraZeneca Lead Sponsor

Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo Collaborator

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility of sequential therapy with FOLFIRI followed by docetaxel/cisplatin in patients with radically resected gastric adenocarcinoma. A randomized phase III trial. [2018] Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting.

2. Greece pubmed.ncbi.nlm.nih.gov

Feasibility study of triplet combination chemotherapy of paclitaxel, cisplatin and S-1 for advanced gastric cancer. [2015] Docetaxel combined with cisplatin and 5-fluorouracil (5-FU) is active in advanced gastric cancer, but not generally accepted because of its substantial toxicities. We conducted a feasibility study of a triplet combination using paclitaxel, cisplatin and S-1 for advanced gastric cancer.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel, cisplatin and 5-fluorouracil combination chemotherapy for unresectable / recurrent gastric cancer. [2015] We investigated the safety of triple combination therapy by addition of Paclitaxel (PTX) to Cisplatin (CDDP) and 5-fluorouracil (5-FU) combination therapy, which was considered the conventional standard therapy for patients with unresectable / recurrent gastric cancer.

4. Germany pubmed.ncbi.nlm.nih.gov

[Patient with stomach cancer with metastases. What is the value of chemotherapy?]. [2013] In comparison with supportive measures alone, chemotherapy in advanced gastric carcinoma is associated with a significant increase in survival and improvement in quality of life. The following substances are considered to be effective and suitable for combination therapy: 5-FU +/- folic acid, cisplatin, irinotecan, etoposide, taxol, and taxotere. In contrast, the effect of doxorubicin and epidoxorubicin is only moderate. Although "second generation" combinations, such as FAMTX, ELF or cisplatin/5-FU, induced higher remission rates as the "first generation" combinations, they failed to improve survival times to any appreciable extent. Currently accepted standard treatment of metastatic gastric carcinoma is infusional 5-FU + cisplatin or ECF. The third generation combinations containing taxane, irinotecan, oxaliplatin appear to be at least equally effective.

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

T-DXd Keeps Shining in Breast Cancer. [2023] The latest phase III data from DESTINY-Breast02 and DESTINY-Breast03 indicate that trastuzumab deruxtecan, or T-DXd, outperforms capecitabine-based chemotherapy and T-DM1 in patients with metastatic HER2-positive breast cancer. According to results from an investigator-initiated trial, TRIO-US B-12 TALENT, T-DXd may also have neoadjuvant potential in HER2-low disease.

6. Thailand pubmed.ncbi.nlm.nih.gov

Low-dose docetaxel/cisplatin - leucovorin and 46 hour infusional fluorouracil in metastatic gastric carcinoma. [2019] Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but with high rates of hematologic toxicity in metastatic gastric cancer cases. To reduce toxicity while maintaining the efficacy of DCF, we investigated low dose docetaxel (D), cispatin (C) - leucovorin and fluorouracil (De Gramont regimen).

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

Phase II study of low-dose docetaxel/fluorouracil/cisplatin in metastatic gastric carcinoma. [2019] In several recent reports, docetaxel (75-85 mg/m2) combined with fluorouracil (5-FU) and cisplatin has shown considerable efficacy but significant toxicities, especially neutropenia, in patients with advanced gastric cancer. The authors tested the efficacy and safety of a lower dose (50 mg/m2) of docetaxel, combined with 5-FU and cisplatin, in metastatic gastric cancer (MGC).

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

A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. [2021] We evaluated the efficacy and safety of cetuximab in combination with XELOX [XELoda® (capecitabine) and OXaliplatin] in advanced gastric cancer (AGC) patients. The objectives were to evaluate overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety of cetuximab plus XELOX.

9. Japan pubmed.ncbi.nlm.nih.gov

Combination docetaxel (Taxotere), fluorouracil, and leucovorin (TFL), as first-line chemotherapy in advanced gastric cancer: a Hellenic Cooperative Oncology Group phase II study. [2022] We assessed the efficacy and safety profile of a docetaxel (Taxotere; Sanofi-Aventis, France), fluorouracil (FU), and leucovorin (LV) combination (TFL), as first-line chemotherapy in patients with advanced gastric cancer.

10. Switzerland pubmed.ncbi.nlm.nih.gov

A phase II study of epirubicin, cisplatin and capecitabine combination chemotherapy in patients with metastatic or advanced gastric cancer. [2015] The purpose of this study was to evaluate the antitumor activity and safety of an epirubicin, cisplatin, and capecitabine (ECX) combination in patients with metastatic or advanced gastric cancer.

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

Docetaxel, Oxaliplatin and Capecitabine (TEX) triplet regimen as adjuvant chemotherapy in resected gastric adenocarcinoma. [2022] Adjuvant chemotherapy after surgery for gastric cancer improves survival but is difficult to administer due to poor tolerance. Combination chemotherapy with Docetaxel (Taxotere), Oxaliplatin (Eloxatin) and Capecitabine (Xeloda) (TEX) is used in the treatment of advanced gastric cancer. The efficacy and tolerability of this regimen (TEX) post resection of gastric cancer have not been studied.

12. Netherlands pubmed.ncbi.nlm.nih.gov

Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study). [2022] Label="INTRODUCTION" NlmCategory="BACKGROUND">In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m2 q3w) to cisplatin (75 mg/m2 q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated.