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.
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
454
Intravenous (IV) Antibody drug conjugate
Administered orally
Administered as an IV
Administered as an IV
Administered as an IV
Administered as an IV
Administered as an IV
Administered orally
Administered as an IV
Research Site
Los Angeles, California, United States
RECRUITINGResearch Site
San Diego, California, United States
WITHDRAWNResearch Site
Santa Rosa, California, United States
RECRUITINGResearch Site
Muncie, Indiana, United States
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.
Time frame: From baseline to progressive disease or death (approximately 1 year)
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.
Time frame: 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 (approximately 1 year)
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 frame: From baseline to PSA response evaluated according to the PCWG3 criteria (approximately 1 year)
Progression free survival (PFS) response (Substudy 4C only)
PFS is defined as time from start of treatment until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.
Time frame: From baseline to progressive disease or death (approximately 1 year)
Progression free survival (PFS)
PFS is defined as time from start of treatment until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.
Time frame: From baseline to progressive disease or death (approximately 1 year)
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 due to any cause.
Time frame: From baseline to progressive disease or death (approximately 1 year)
Disease Control Rate (DCR)
DCR at 12 and 24 weeks is defined as the percentage of participants who prior to Progression of Disease (PD) and starting anticancer therapy have either at least one visit response of Complete response (CR)/Partial response (PR) or 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.
Time frame: At approximately 1 year
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.
Time frame: From baseline to progressive disease or death (approximately 1 year)
Pharmacokinetics of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): Maximum plasma concentration of the drug (Cmax)
The concentration in plasma will be determined.
Time frame: At predefined intervals throughout the treatment period (approximately 1 year)
Pharmacokinetics of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): The time taken to reach the maximum concentration (Tmax)
The concentration in plasma will be determined.
Time frame: At predefined intervals throughout the treatment period (approximately 1 year)
Pharmacokinetic Parameter of Dato-DXd (all substudies) and 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.
Time frame: At predefined intervals throughout the treatment period (approximately 1 year)
Plasma concentration of Total anti-TROP2 antibody
Expression of TROP2 will be measured in blood sample
Time frame: Throughout the treatment period at pre-defined intervals (approximately 1 year)
Plasma concentration of MAAA-1181a
The concentration in plasma will be determined (Cmax will be derived).
Time frame: Throughout the treatment period at pre-defined intervals (approximately 1 year)
Anti Drug Antibody (ADA) for Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6)
Whole blood samples for determination of ADA in plasma will be collected; Percentage of patients who develop ADA
Time frame: Throughout the treatment period at pre-defined intervals and including the safety follow-up period (approximately 1 year)
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 due to any cause.
Time frame: From baseline to radiographic progression or death (approximately 1 year)
PSA progression (Substudy 3)
PSA progression is defined as an increase in PSA (after Week 12) of ≥25% greater than the nadir and an absolute increase of at least 2 ng/mL above nadir.
Time frame: From baseline to PSA response evaluated according to the PCWG3 criteria (approximately 1 year)
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.
Time frame: From baseline to CA-125 response evaluated according to the GCIG criteria (approximately 1 year)
Overall survival (OS) (Substudy 4)
OS is defined as time from start of treatment until death due to any cause.
Time frame: From baseline to death (approximately 1 year)
AstraZeneca Clinical Study Information Center
CONTACT
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Research Site
Kansas City, Kansas, United States
WITHDRAWNResearch Site
Boston, Massachusetts, United States
WITHDRAWNResearch Site
Boston, Massachusetts, United States
COMPLETEDResearch Site
Grand Rapids, Michigan, United States
RECRUITINGResearch Site
East Brunswick, New Jersey, United States
RECRUITINGResearch Site
Albuquerque, New Mexico, United States
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