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NCT05489211PHASE2Recruiting

Study of Dato-DXd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

AstraZeneca

Start Date

9/6/2022

Completion Date

10/1/2027

Summary

TROPION-PanTumor03 will investigate the safety, tolerability, and anti-tumour activity of Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination with Anticancer Agents in Patients with Advanced/Metastatic Solid Tumours.

Detailed Description

This Phase II, open-label, uncontrolled, multicentre study evaluating the efficacy and safety of Dato-DXd as monotherapy (MONO) and in combination with anticancer agents (COMBO) in various advanced solid tumour types. This study has a modular design, as such a master protocol with independent substudies enables simultaneous evaluation of the safety profile, recommended Phase II dose (RP2D), and efficacy of Dato-DXd in multiple disease populations and treatment combinations. This study will evaluate various solid tumour types, including endometrial cancer (Substudy 1), gastric cancer (Substudy 2), metastatic castration-resistant prostate cancer (mCRPC) (Substudy 3), ovarian cancer (Substudy 4), colorectal cancer (CRC) (Substudy 5), urothelial cancer (Substudy 6), and biliary tract cancer (Substudy 7) in the advanced or metastatic setting. Within each substudy, Dato-DXd will be evaluated as monotherapy (for all substudies except Substudy 2) and in combination with approved or novel anticancer agents that may be active in the tumour type being evaluated (for all substudies except Substudy 1 and Substudy 7).

Eligibility Criteria

Age Range: 18 years to 130 years

Key Inclusion Criteria: There are additional substudy requirements not reflected here. This list is based solely on the master CSP * Male and female, ≥ 18 years * Documented advanced or metastatic malignancy * Eastern Cooperative Oncology Group performance status of 0 or 1 with no deterioration over the 2 weeks prior to baseline or day of first dosing * All participants must provide a tumour sample for tissue-based analysis * At least 1 measurable lesion not previously irradiated, except Substudy 3 (Prostate Cancer) which allows participants with non measurable bone metastatic disease * Adequate bone marrow reserve and organ function * Minimum life expectancy of 12 weeks * 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 * All women of childbearing potential must have a negative serum pregnancy test documented during screening * Female participants must be 1 year post-menopausal, surgically sterile, or using 1 highly effective form of birth control. Female participants must not donate, or retrieve for their own use, ova at any time during this study * Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile, avoid intercourse, or use a highly effective method of contraception. Male participants must not freeze or donate sperm at any time during this study. * Capable of giving signed informed consent * Provision of signed and dated written optional genetic research informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative Key Exclusion Criteria: * Any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol * History of another primary malignancy except for adequately resected basal cell carcinoma or in situ squamous cell carcinoma of the skin, or other solid malignancy treated with curative intent * Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved * Irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator, for example hearing loss * Spinal cord compression or brain metastases unless treated * Leptomeningeal carcinomatosis * Clinically significant corneal disease * Active hepatitis or uncontrolled hepatitis B or C virus infection * Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, for example prodromal symptoms * Known HIV infection that is not well controlled * Known active tuberculosis infection * Mean resting corrected QTcF \> 470 ms * In the judgement of the investigator, history of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause TdP * In the judgement of the investigator, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives * Uncontrolled or significant cardiac diseases * History of non-infectious Interstitial lung disease (ILD)/pneumonitis, including radiation pneumonitis that required steroids * Has severe pulmonary function compromise * Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period * Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention * Prior exposure to anticancer therapies without an adequate treatment washout period prior to enrolment or any concurrent anticancer treatment * Palliative radiotherapy with a limited field of radiation within ≤ 2 weeks or to more than 30% of the bone marrow within ≤ 4 weeks before the first dose of study intervention * Major surgical procedure or significant traumatic injury within ≤ 3 weeks of the first dose of study intervention or an anticipated need for major surgery during the study * Prior treatment with TROP2-directed therapies or other antibody-drug conjugate (ADCs) with deruxtecan payload * Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention * Previous treatment in the present study * Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to first dose of study intervention or concurrent enrolment in another clinical study * Severe hypersensitivity to Dato-DXd or any of the excipients, including but not limited to polysorbate 80 or other monoclonal antibodies * Involvement in the planning and/or conduct of the study * Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements * Females that are pregnant, breastfeeding, or planning to become pregnant * Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of Dato-DXd

Interventions

DRUG

Datopotamab deruxtecan (Dato-DXd)

DRUG

Capecitabine

DRUG

5-Fluorouracil

DRUG

Volrustomig

DRUG

Carboplatin

DRUG

Bevacizumab

DRUG

Rilvegostomig

DRUG

Prednisone/ prednisolone

DRUG

Cisplatin

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Conditions

Endometrial CancerGastric CancerMetastatic Castration-resistant Prostate CancerOvarian CancerColorectal CancerUrothelial CancerBiliary Tract Cancer

Locations

Research Site

Los Angeles, California 90095

United States

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San Diego, California 92103

United States

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Santa Rosa, California 95403

United States

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Muncie, Indiana 47303

United States

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Kansas City, Kansas 66160

United States

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Boston, Massachusetts 02114

United States

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Boston, Massachusetts 02215

United States

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Grand Rapids, Michigan 49503

United States

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East Brunswick, New Jersey 08816

United States

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Albuquerque, New Mexico 87109

United States

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Commack, New York 11725

United States

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Cincinnati, Ohio 45219

United States

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Columbus, Ohio 43219

United States

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Portland, Oregon 97239

United States

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Nashville, Tennessee 37203

United States

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Nashville, Tennessee 37232

United States

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Houston, Texas 77030

United States

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Madison, Wisconsin 53792

United States

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Toronto, Ontario M4N 3M5

Canada

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Toronto, Ontario M5G 2M9

Canada

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Montreal, Quebec H2X 0A9

Canada

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Montreal, Quebec H4A 3J1

Canada

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Québec, Quebec G1J 1Z4

Canada

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Changsha, 410013

China

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Chongqing, 400030

China

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Guangzhou, 510060

China

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Guangzhou, 510060

China

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Guangzhou, 510120

China

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Hangzhou, 310020

China

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Hefei, 230001

China

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Shanghai, 200032

China

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Shanghai, 200032

China

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Shenyang, 110016

China

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Wuhan, 430030

China

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Wuhan, 430079

China

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Xi'an, 710000

China

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Zhengzhou, 450052

China

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Bordeaux, 33076

France

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Lyon, 69373

France

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Marseille, 13273

France

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Suresnes, 92150

France

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Berlin, 10117

Germany

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Essen, 45136

Germany

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Hanover, 30625

Germany

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München, 81377

Germany

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Regensburg, 93053

Germany

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Florence, 50139

Italy

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Genova, 16132

Italy

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Milan, 20132

Italy

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Milan, 20141

Italy

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Milan, 20162

Italy

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Naples, 80131

Italy

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Rome, 00168

Italy

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Chūōku, 104-0045

Japan

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Kashiwa, 277-8577

Japan

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Kōtoku, 135-8550

Japan

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Nagoya, 464-8681

Japan

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Shinagawa-ku, 142-8666

Japan

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Suita-shi, 565-0871

Japan

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Gliwice, 44-102

Poland

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Krakow, 31-501

Poland

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Lodz, 92-213

Poland

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Poznan, 61-866

Poland

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Warsaw, 02-781

Poland

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Seoul, 03722

South Korea

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Seoul, 05505

South Korea

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Seoul, 06351

South Korea

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Seoul, 110-744

South Korea

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Barcelona, 8035

Spain

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Córdoba, 14004

Spain

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Madrid, 28046

Spain

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Málaga, 29010

Spain

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Pamplona, 31008

Spain

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Seville, 41013

Spain

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Basel, 4031

Switzerland

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Bellinzona, 6500

Switzerland

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Sankt Gallen, 9007

Switzerland

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Liou Ying Township, 736

Taiwan

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Taipei, 100

Taiwan

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Taipei, 11259

Taiwan

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Taipei, 112

Taiwan

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Taoyuan, 333

Taiwan

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Ankara, 06620

Turkey (Türkiye)

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Ankara, 06800

Turkey (Türkiye)

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Cordaleo, 35575

Turkey (Türkiye)

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Edirne, 22030

Turkey (Türkiye)

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Kadıkoy/Istanbul, 34722

Turkey (Türkiye)

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Konya, 42080

Turkey (Türkiye)

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Pamukkale, 20070

Turkey (Türkiye)

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Samsun, 55139

Turkey (Türkiye)

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Cambridge, CB2 0QQ

United Kingdom

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Dundee, DD1 9SY

United Kingdom

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London, EC1A 7BE

United Kingdom

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London, NW1 2PG

United Kingdom

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London, SE1 9RT

United Kingdom

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Manchester, M20 4BX

United Kingdom