Dato-DXd Combination Therapy for Advanced Cancers

Recruiting at57 trial locations

Overseen by Global Clinical Lead, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AstraZeneca

Must not be taking: Chloroquine, Hydroxychloroquine, others

Disqualifiers: Hepatitis, HIV, Tuberculosis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing Dato-DXd, a targeted cancer treatment, in patients with advanced or metastatic solid tumors. The treatment aims to deliver chemotherapy directly to cancer cells, helping to kill them while reducing harm to healthy cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there is a requirement for a washout period (time without taking certain medications) for prior anticancer therapies and chloroquine/hydroxychloroquine before enrollment.

What data supports the effectiveness of the drug Dato-DXd Combination Therapy for Advanced Cancers?

Research shows that Dato-DXd, a TROP2-directed antibody-drug conjugate, has shown promising results in treating various advanced cancers. In trials, it demonstrated encouraging response rates in breast cancer and non-small cell lung cancer, with manageable side effects, suggesting its potential effectiveness in these conditions. ^{1 2 3 4 5}

What makes the drug Dato-DXd unique for treating advanced cancers?

Dato-DXd is unique because it is an antibody-drug conjugate that targets TROP2, a protein often found on cancer cells, and delivers a topoisomerase I inhibitor directly to the tumor, potentially increasing effectiveness and reducing side effects compared to traditional chemotherapy. ^{1 2 3 6 7}

Research Team

Global Clinical Lead, MD

Principal Investigator

AstraZeneca

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors, such as biliary tract, colorectal, ovarian, bladder, endometrial, stomach or prostate cancer. Participants must have a life expectancy of at least 12 weeks and at least one measurable lesion not previously treated with radiation. They should have good organ function but can't join if they're pregnant, have severe allergies to certain drugs in the study, uncontrolled infections or significant heart diseases.

Inclusion Criteria

All women of childbearing potential must have a negative serum pregnancy test documented during screening

I can provide a sample of my tumor for testing.

At the time of screening, contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

Exclusion Criteria

My brain or spinal cord cancer has been treated.

My cancer has spread to the lining of my brain and spinal cord.

I do not have active or uncontrolled hepatitis B or C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dato-DXd as monotherapy or in combination with anticancer agents across various substudies

Approximately 1 year

Predefined intervals throughout the treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 to 90 days after discontinuation of study interventions

Extension

Optional continuation of treatment for participants showing benefit

Long-term

Treatment Details

Interventions

• 5-Fluorouracil (Chemotherapy)
• AZD5305 (Small Molecule Inhibitor)
• Bevacizumab (Angiogenesis Inhibitor)
• Capecitabine (Chemotherapy)
• Carboplatin (Chemotherapy Agent)
• Datopotamab deruxtecan (Dato-DXd) (Antibody-Drug Conjugate)
• Durvalumab (Immunotherapy Agent)
• Leucovorin LV (Chemotherapy)
• Nivolumab (Immunotherapy Agent)

Trial Overview The TROPION-PanTumor03 trial is testing Datopotamab Deruxtecan (Dato-DXd) alone and combined with other anti-cancer agents like Bevacizumab and Durvalumab. The goal is to assess safety and how well these treatments work against various advanced cancers.

Participant Groups

Group I: Substudy-7A Experimental Treatment 1 Intervention

Dato-DXd will be evaluated as monotherapy

Group II: Substudy-6D Experimental Treatment 3 Interventions

Dato-DXd in combination with carboplatin or cisplatin will be evaluated

Group III: Substudy-6C Experimental Treatment 1 Intervention

Dato-DXd will be evaluated as monotherapy

Group IV: Substudy-6B Experimental Treatment 2 Interventions

Data-DXd in combination with rilvegostomig (AZD2936) will be evaluated

Group V: Substudy-6A Experimental Treatment 2 Interventions

Dato-DXd in combination with volrustomig (MEDI5752) will be evaluated

Group VI: Substudy-5B Experimental Treatment 5 Interventions

Dato-DXd + 5-FU + LV + bevacizumab OR Dato-DXd + capecitabine + bevacizumab will be evaluated

Group VII: Substudy-5A Experimental Treatment 1 Intervention

Dato-DXd will be evaluated as monotherapy

Group VIII: Substudy-4C Experimental Treatment 3 Interventions

Dato-DXd in combination with carboplatin + bevacizumab followed by Dato-DXd + bevacizumab will be evaluated

Group IX: Substudy-4A Experimental Treatment 1 Intervention

Dato-DXd will be evaluated as monotherapy

Group X: Substudy-3C Experimental Treatment 2 Interventions

Dato-DXd will be evaluated in combination with prednisone/prednisolone

Group XI: Substudy-3A Experimental Treatment 1 Intervention

Dato-DXd will be evaluated as monotherapy

Group XII: Substudy-2B Experimental Treatment 2 Interventions

Dato-DXd in combination with 5-FU will be evaluated

Group XIII: Substudy-2A Experimental Treatment 2 Interventions

Dato-DXd in combination with capecitabine will be evaluated

Group XIV: Substudy-1A Experimental Treatment 1 Intervention

Dato-DXd will be evaluated as monotherapy

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Daiichi Sankyo, Inc.

Industry Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi 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

Datopotamab deruxtecan (Dato-DXd) is a promising new treatment for patients with metastatic HR+/HER2- breast cancer, particularly for those who have limited options after endocrine therapy and chemotherapy.

The ongoing phase III TROPION-Breast01 study is comparing the efficacy and safety of Dato-DXd against standard chemotherapy in patients who have already received one or two lines of systemic treatment, aiming to improve outcomes in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. Bardia, A., Jhaveri, K., Kalinsky, K., et al.[2023]

In a phase I trial, the TROP2-directed antibody-drug conjugate datopotamab deruxtecan showed promising activity in patients with advanced or metastatic non-small cell lung cancer, with nearly 25% of participants responding to the treatment.

The treatment was associated with manageable side effects, suggesting it could be a safe option for patients with this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROP2 ADC Intrigues in NSCLC. [2021]

Datopotamab deruxtecan (Dato-DXd) demonstrated promising antitumor activity in patients with advanced non-small-cell lung cancer (NSCLC), achieving an objective response rate of 26% and a median duration of response of 10.5 months in a study involving 210 patients.

The treatment was generally well-tolerated, with a maximum tolerated dose of 8 mg/kg and a recommended dose of 6 mg/kg, although some patients experienced treatment-emergent adverse events, including nausea and interstitial lung disease, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01. Shimizu, T., Sands, J., Yoh, K., et al.[2023]

In a phase I trial, datopotamab deruxtecan showed promising response rates, with 34% of patients with advanced or metastatic triple-negative breast cancer experiencing a complete or partial response.

The treatment was found to have manageable toxicity, indicating it may be a safe option for patients who have not responded to multiple previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Very Compelling" Results for ADC in TNBC Trial. [2022]

Sacituzumab govitecan (SG) is a TROP-2-directed antibody drug conjugate that has shown significant improvements in progression-free survival and overall survival compared to traditional chemotherapy in patients with pretreated metastatic triple-negative breast cancer, leading to its regulatory approval.

Datopotamab deruxtecan (Dato-DXd), another TROP-2 ADC, has demonstrated preliminary efficacy in metastatic triple-negative breast cancer and is currently being evaluated in phase III trials, suggesting that these novel therapies may offer enhanced effectiveness with reduced side effects in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates targeting TROP-2: Clinical development in metastatic breast cancer. Shastry, M., Jacob, S., Rugo, HS., et al.[2022]

The phase III DESTINY-Breast04 trial demonstrated that trastuzumab deruxtecan (T-DXd) is effective for patients with inoperable or metastatic HER2-low breast cancer, providing a new treatment option for this group.

Given the limited treatment options available for patients with HER2-low breast cancer, T-DXd is recommended as a new standard of care, highlighting its significance in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-DXd: New Standard for HER2-Low Breast Cancer. [2022]

In an expanded-access study involving 64 patients with HER2-positive gastric or gastroesophageal junction adenocarcinomas, trastuzumab deruxtecan (T-DXd) was administered safely, with no new safety concerns identified prior to its marketing approval in Japan.

Serious adverse events (SAEs) were reported in 26.6% of patients, with febrile neutropenia being the most common; however, drug-related SAEs led to death in only one patient, indicating a manageable safety profile for T-DXd.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in patients with locally advanced or metastatic HER2-positive gastric cancer: a multicenter, open-label, expanded-access study. Shitara, K., Yamaguchi, K., Muro, K., et al.[2023]

References

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

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. [2023]

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

TROP2 ADC Intrigues in NSCLC. [2021]

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

First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01. [2023]

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

"Very Compelling" Results for ADC in TNBC Trial. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates targeting TROP-2: Clinical development in metastatic breast cancer. [2022]

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

T-DXd: New Standard for HER2-Low Breast Cancer. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in patients with locally advanced or metastatic HER2-positive gastric cancer: a multicenter, open-label, expanded-access study. [2023]