Dato-DXd Combination Therapy for Advanced Cancers

Recruiting at 72 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Chloroquine, Hydroxychloroquine, others

Disqualifiers: Hepatitis, HIV, Tuberculosis, 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 1 year

582 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial researches a new treatment called Datopotamab Deruxtecan (Dato-DXd) for individuals with advanced or metastatic solid tumors. The study aims to assess the safety and effectiveness of Dato-DXd, both alone and in combination with other cancer-fighting drugs. Several groups in this trial test different combinations, such as Dato-DXd with carboplatin or with volrustomig. This trial may suit individuals with advanced cancers whose tumors have spread and have not responded to previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In earlier studies, datopotamab deruxtecan (Dato-DXd) demonstrated promising safety and effectiveness in patients with advanced cancers. Research has shown that Dato-DXd is generally well-tolerated, whether used alone or with other cancer drugs. For instance, when used by itself, patients experienced manageable side effects.

When combined with treatments like carboplatin and bevacizumab, Dato-DXd has also proven safe and effective, supporting its use in treating various advanced cancers. Studies indicate that patients receiving these combinations generally tolerated the treatment well. Additionally, combining Dato-DXd with drugs like volrustomig also supported its safety in patients with advanced cancer.

While specific side effects can vary, the treatment has been linked to improvements in progression-free survival, meaning the cancer does not worsen for a longer time compared to some other treatments. This suggests that while side effects may occur, the potential benefits of the treatment could outweigh the risks for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Dato-DXd because it represents a novel approach for treating advanced cancers. Unlike traditional chemotherapy that attacks all rapidly dividing cells, Dato-DXd is an antibody-drug conjugate, combining targeted delivery with a potent anti-cancer payload. This means it can directly target cancer cells more precisely, potentially reducing damage to healthy cells and minimizing side effects. Additionally, its combination with other agents like carboplatin, bevacizumab, and innovative drugs such as volrustomig and rilvegostomig may enhance its effectiveness by attacking cancer from multiple fronts. This multi-pronged strategy could offer new hope for patients with difficult-to-treat cancers.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research shows that datopotamab deruxtecan (Dato-DXd) holds promise for treating advanced cancers. This trial will evaluate Dato-DXd in various treatment arms. Some participants will receive Dato-DXd as monotherapy, while others will receive it with additional drugs. For instance, one arm will evaluate Dato-DXd with carboplatin, which damages cancer cell DNA, leading to cell death. Another arm will assess the combination of Dato-DXd with bevacizumab, which increased effectiveness in early tests. Additionally, Dato-DXd combined with 5-Fluorouracil (5-FU) will be evaluated for its potential to treat stomach and other solid tumors. Overall, evidence supports Dato-DXd's potential to slow cancer growth in various tumor types, whether used alone or with other drugs. ^{1 6 7 8 9}

Who Is on the Research Team?

Global Clinical Lead, MD

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil
• AZD5305
• Bevacizumab
• Capecitabine
• Carboplatin
• Datopotamab deruxtecan (Dato-DXd)
• Durvalumab
• Leucovorin LV
• Nivolumab

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05489211

NCT05489211 | Study of Dato-Dxd as Monotherapy and in ... This study will evaluate various solid tumour types, including endometrial cancer (Substudy 1), gastric cancer (Substudy 2), metastatic castration-resistant ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39761483/

Results From the Phase II TROPION-Lung05 Study Datopotamab Deruxtecan in Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study.

3. asco.org asco.org/abstracts-presentations/ABSTRACT332873

A randomized, phase 3 study of datopotamab deruxtecan ... This phase 3 study (NCT04656652) will compare the efficacy of Dato-DXd with that of docetaxel as 2/3L therapy in patients with advanced/metastatic NSCLC.

4. onclive.com onclive.com/view/datopotamab-deruxtecan-significantly-improves-pfs-in-advanced-nsclc

Datopotamab Deruxtecan Significantly Improves PFS in ... Datopotamab deruxtecan provided a statistically significant improvement in progression-free survival compared with standard-of-care docetaxel in ...

5. academic.oup.com academic.oup.com/oncolo/article/30/3/oyaf031/8096319

Prophylaxis, clinical management, and monitoring of ... Datopotamab deruxtecan (Dato-DXd) is a novel trophoblast cell surface antigen 2-directed antibody-drug conjugate undergoing clinical ...

6. dede.www.astrazenecaclinicaltrials.com dede.www.astrazenecaclinicaltrials.com/study/D926UC00001/

Study of Dato-Dxd as Monotherapy and in Combination ... TROPION-PanTumor03 will investigate the safety, tolerability, and anti-tumour activity of Datopotamab Deruxtecan (Dato-DXd) as Monotherapy ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40700616/

Datopotamab deruxtecan-associated select adverse events Dato-DXd demonstrated statistically significant improvement in median progression-free survival (mPFS) over docetaxel in patients with ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11941615/

Camptothein-Based Anti-Cancer Therapies and Strategies ... Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study.

9. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D926UC00001/?Latitude=42.733883&Longitude=25.48583&LocationName=Bulgaria&MileRadius=100

Study of Dato-Dxd as Monotherapy and in Combination ... TROPION-PanTumor03 will investigate the safety, tolerability, and anti-tumour activity of Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination ...