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

Colorectal Cancer Clinical Trial

Official title:

A Phase II, Multicentre, Open-label, Master Protocol to Evaluate the Efficacy and Safety of Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination With Anticancer Agents in Patients With Advanced/Metastatic Solid Tumours

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05489211
• Other study ID #: D926UC00001
• Secondary ID: 2022-000776-19
• Status: Recruiting
• Phase: Phase 2
• Start date: September 6, 2022
• Est. completion date: August 19, 2026

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 (Gastric Cancer) and Substudy 6 (Urothelial Cancer) and in combination with approved or novel anticancer agents that may be active in the tumour type being evaluated (for all substudies except Substudy 7).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 531
• Est. completion date: August 19, 2026
• Est. primary completion date: August 19, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Key Inclusion Criteria:

• 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

• 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

• Active TB infection

• Significant cardiac diseases

• History of non-infectious Interstitial lung disease (ILD)/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

• 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 Anti-drug antibody, ADC Antibody-drug conjugate (ADCs), other ADCs with deruxtecan payload

• Severe hypersensitivity to monoclonal antibodies

• Pregnant, breastfeeding, planning to become pregnant

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms
• Colorectal Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Gastric Cancer
• Metastatic Castration-resistant Prostate Cancer
• Ovarian Cancer
• Urothelial Cancer

Intervention

Drug:
• Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
• Saruparib
Oral poly ADP ribose polymerase (PARP) inhibitor
• Durvalumab
Administered as an IV
• Capecitabine
Administered orally
• 5-Fluorouracil
Administered as an IV
• Volrustomig
Administered as an IV
• Carboplatin
Administered as an IV
• Leucovorin LV
Administered as an IV
• Bevacizumab
Administered as an IV
• Rilvegostomig
Administered as an IV
• Prednisone/ prednisolone
Administered orally

Locations

Country	Name	City	State
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
China	Research Site	Changsha
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Zhengzhou
France	Research Site	Bordeaux
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Suresnes
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Hannover
Germany	Research Site	München
Germany	Research Site	Regensburg
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Rome
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa
Japan	Research Site	Koto-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Suita-shi
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Poland	Research Site	Gliwice
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Pamplona
Spain	Research Site	Sevilla
Switzerland	Research Site	Basel
Switzerland	Research Site	Bellinzona
Switzerland	Research Site	St. Gallen
Taiwan	Research Site	Liou Ying Township
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Kadikoy/Istanbul
Turkey	Research Site	Karsiyaka
Turkey	Research Site	Konya
Turkey	Research Site	Pamukkale
Turkey	Research Site	Samsun
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Commack	New York
United States	Research Site	East Brunswick	New Jersey
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Houston	Texas
United States	Research Site	Kansas City	Kansas
United States	Research Site	Los Angeles	California
United States	Research Site	Madison	Wisconsin
United States	Research Site	Muncie	Indiana
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	Portland	Oregon
United States	Research Site	San Diego	California
United States	Research Site	Santa Rosa	California

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Proportion of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1.	From baseline to progressive disease or death (approximately 1 year)
Primary	The number of subjects with adverse events/serious adverse events	Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline.	Throughout the treatment and the safety follow-up period 28 [+ 7] days after the discontinuation of all study interventions, except durvalumab, nivolumab, and bevacizumab for which it will be 90 [+ 7] days (approximatelt 1 year)
Primary	PSA50 response (Substudy 3 only)	Proportion of participants achieving a = 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later.	Time to PSA progression is defined as the time from randomization to PSA progression per PCWG3 criteria (up to 12 weeks)
Secondary	Progression free survival (PFS)	PFS is defined as time from start of treatment until progression per RECIST 1.1 as assessed by the investigator.	From baseline to progressive disease or death (approximately 1 year)
Secondary	Duration Of Response (DOR)	DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by the investigator or death.	From baseline to progressive disease or death (approximately 1 year)
Secondary	Disease Control Rate (DCR)	DCR at 12 and 24 weeks is defined as the percentage of participants who have a Complete response (CR) or Partial response (PR) in the first 13 and 25 weeks or who have Stable disease (SD) for at least 11 and 23 weeks after the date of first dose respectively, per RECIST 1.1 as assessed by the investigator at local site and derived from the raw tumour data.	at 12 and 24 weeks
Secondary	Best percentage change in tumour size	The best percentage change from baseline in tumour size will be derived as the maximum reduction from baseline or (in the absence of reduction) the minimum increase from baseline.	From baseline to progressive disease or death (approximately 1 year)
Secondary	Anti Drug Antibody (ADA) for Dato-DXd (all substudies), Durvalumab (substudy 1), volrustomig and rilvegostomig (substudy 6)	Whole blood samples for determination of ADA in plasma will be collected; Percentage of patients who develop ADA	Throughout the treatment period at pre-defined intervals and including the safety follow-up period (approximately 1 year)
Secondary	Pharmacokinetics of Dato-DXd (all substudies), durvalumab (substudy 1) and AZD5305 (substudy 1, substudy 3, substudy 4), volrustomig and rilvegostomig (substudy 6): Maximum plasma concentration of the drug (Cmax)	The concentration in plasma will be determined.	At predefined intervals throughout the treatment period (approximately 1 year)
Secondary	Pharmacokinetics of Dato-DXd (all substudies), durvalumab (substudy 1) and AZD5305 (substudy 1, substudy 3, substudy 4), volrustomig and rilvegostomig (substudy 6): The time taken to reach the maximum concentration (Tmax)	The concentration in plasma will be determined.	At predefined intervals throughout the treatment period (approximately 1 year)
Secondary	Pharmacokinetic Parameter of Dato-DXd (all substudies), durvalumab (substudy 1) and AZD5305 (substudy 1, substudy 3, substudy 4), volrustomig and rilvegostomig (substudy 6): Area under the plasma concentration- time curve (AUC)	The concentration in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.	At predefined intervals throughout the treatment period (approximately 1 year)
Secondary	Plasma concentration of Total anti-TROP2 antibody	Expression of TROP2 will be measured in blood sample	Throughout the treatment period at pre-defined intervals (approximately 1 year)
Secondary	Plasma concentration of MAAA-1181a	The concentration in plasma will be determined (Cmax will be derived).	Throughout the treatment period at pre-defined intervals (approximately 1 year)
Secondary	Radiographic PFS (substudy 3)	PFS is defined as time from start of treatment until radiographic progression per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone) as assessed by the investigator or death.	From baseline to radiographic progression or death (approximately 1 year)
Secondary	Overall survival (OS) (substudy 4)	OS is defined as time from start of treatment until death.	From baseline to death (approximately 1 year)
Secondary	CA-125 response (Substudy 4)	Proportion of participants achieving a > 50% reduction in CA-125 levels from a pre-treatment sample confirmed and maintained for at least 28 days.	From baseline to CA-125 response evaluated according to the GCIG criteria (up to 12 weeks)