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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05489211
Recruitment Status : Recruiting
First Posted : August 5, 2022
Last Update Posted : September 19, 2022
Sponsor:
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
AstraZeneca

Brief 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.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Gastric Cancer Metastatic Castration-resistant Prostate Cancer Ovarian Cancer Colorectal Cancer Drug: Datopotamab deruxtecan (Dato-DXd) Drug: AZD5305 Drug: Durvalumab Drug: Capecitabine Drug: 5-Fluorouracil Drug: Nivolumab Drug: Carboplatin Drug: Leucovorin LV Drug: Bevacizumab Phase 2

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), and colorectal cancer (CRC) (Substudy 5) 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 in combination with approved or novel anticancer agents that may be active in the tumour type being evaluated.(AZD5305, Durvalumab).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 531 participants
Allocation: N/A
Intervention Model: Parallel Assignment
Intervention Model Description:

Within each substudy, Dato-DXd will be evaluated as monotherapy (for all substudies except Substudy 2, Gastric Cancer) and in combination with approved or novel anticancer agents that may be active in the tumour type being evaluated. Substudy 2 (2A, 2B) will be randomised and other substudies will be assigned.

Substudy 1 (Endometrial Cancer); MONO: Dato-DXd monotherapy COMBO; Dato-DXd + durvalumab, Dato-DXd + AZD5305, Dato-DXd + durvalumab +AZD5305

Substudy 2 (Gastric Cancer); Dato-DXd + capecitabine, Dato-DXd + 5-fluorouracil (5-FU), Dato-DXd + chemotherapy (capecitabine or 5-FU) + nivolumab

Substudy 3 (mCRPC); MONO and Dato-DXd + AZD5305

Substudy 4 (Ovarian Cancer); MONO and Dato-DXd + carboplatin, Dato-DXd + AZD5305

Substudy 5 (CRC); MONO and Dato-DXd + 5-FU + leucovorin (LV) + bevacizumab or Dato-DXd + capecitabine + bevacizumab

Masking: None (Open Label)
Masking Description: The study is open label. Patients will be assigned treatment in all Substudies except for the cohort 2A and 2B in Gastric Substudy where patients will be randomized.
Primary Purpose: Treatment
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 (TROPION-PanTumor03)
Actual Study Start Date : September 6, 2022
Estimated Primary Completion Date : May 2, 2025
Estimated Study Completion Date : May 2, 2025


Arm Intervention/treatment
Experimental: Substudy-1A
Dato-DXd will be evaluated as monotherapy
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Experimental: Substudy-1B
Dato-Dxd in combination with Durvalumab will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Drug: Durvalumab
Administered as an IV
Other Names:
  • MEDI4736
  • IMFINZI

Experimental: Substudy-1C
Dato-Dxd in combination with AZD5305 will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Experimental: Substudy-1D
Dato-Dxd in combination with Durvalumab + AZD5305 will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Drug: AZD5305
Oral poly ADP ribose polymerase (PARP) inhibitor

Drug: Durvalumab
Administered as an IV
Other Names:
  • MEDI4736
  • IMFINZI

Experimental: Substudy-2A
Dato-DXd in combination with capecitabine will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Drug: Capecitabine
Administered orally
Other Name: Xeloda

Experimental: Substudy-2B
Dato-DXd in combination with 5-FU will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Drug: 5-Fluorouracil
Administered as an IV
Other Name: Adrucil

Experimental: Substudy-2C
Dato-DXd in combination with chemotherapy (capecitabine or 5-FU) + nivolumab will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Drug: Capecitabine
Administered orally
Other Name: Xeloda

Drug: 5-Fluorouracil
Administered as an IV
Other Name: Adrucil

Drug: Nivolumab
Administered as an IV
Other Name: OPDIVO

Experimental: Substudy-3A
Dato-DXd will be evaluated as monotherapy
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Experimental: Substudy-3B
Dato-DXd in combination with AZD5305 will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Drug: AZD5305
Oral poly ADP ribose polymerase (PARP) inhibitor

Experimental: Substudy-4A
Dato DXd will be evaluated as monotherapy
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Experimental: Substudy-4B
Dato-DXd in combination with carboplatin and Dato-DXd + AZD5305 will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Drug: AZD5305
Oral poly ADP ribose polymerase (PARP) inhibitor

Drug: Carboplatin
Administered as an IV
Other Name: Paraplatin

Experimental: Substudy-5A
Dato-DXd will be evaluated as monotherapy
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Experimental: Substudy-5B
Dato-DXd + 5-FU + LV + bevacizumab OR Dato-DXd + capecitabine + bevacizumab will be evaluated
Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a

Drug: Capecitabine
Administered orally
Other Name: Xeloda

Drug: 5-Fluorouracil
Administered as an IV
Other Name: Adrucil

Drug: Leucovorin LV
Administered as an IV
Other Name: Folinic acid

Drug: Bevacizumab
Administered as an IV
Other Name: Avastin




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: From baseline to progressive disease or death (approximately 1 year) ]
    Best response until progression, as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.

  2. The number of subjects with adverse events/serious adverse events [ 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 (approximatelt 1 year) ]
    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.


Secondary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: From baseline to progressive disease or death (approximately 1 year) ]
    PFS is defined as time from start of treatment until progression per RECIST 1.1 as assessed by the investigator.

  2. Duration Of Response (DOR) [ Time Frame: From baseline to progressive disease or death (approximately 1 year) ]
    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.

  3. Disease Control Rate (DCR) [ Time Frame: at 12 and 24 weeks ]
    DCR at 12 and 24 weeks is defined as the percentage of participants who have a confirmed 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.

  4. Best percentage change in tumour size [ Time Frame: From baseline to progressive disease or death (approximately 1 year) ]
    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.

  5. Anti Drug Antibody (ADA) [ Time Frame: Throughout the treatment period at pre-defined intervals and including the safety follow-up period (approximately 1 year) ]
    Whole blood samples for determination of ADA for Dato-DXd in plasma will be collected in patients receiving Dato-DXd;Percentage of patients who develop ADA for Dato-Dxd

  6. Pharmacokinetics of Dato-DXd, Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 1 year) ]
    The concentration of Dato-Dxd in plasma will be determined (Cmax will be derived).

  7. Pharmacokinetics of Dato-DXd, The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 1 year) ]
    The concentration of Dato-DXd in plasma will be determined (Tmax will be derived).

  8. Pharmacokinetic Parameter: Area under the plasma concentration- time curve (AUC) [ Time Frame: At predefined intervals throughout the treatment period (approximately 1 year) ]
    The concentration of Dato-Dxd 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.

  9. Plasma concentration of Total anti-TROP2 antibody [ Time Frame: Throughout the treatment period at pre-defined intervals (approximately 1 year) ]
    Expression of TROP2 will be measured in blood sample

  10. Plasma concentration of MAAA-1181a [ Time Frame: Throughout the treatment period at pre-defined intervals (approximately 1 year) ]
    The concentration in plasma will be determined (Cmax will be derived).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male and female, ≥ 18 years
  • Histologically or cytologically documented advanced or metastatic malignancy.
  • At least 1 lesion not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline Substudy 3 (mCRPC) allows enrolment of participants with non measurable (by RECIST 1.1) bone metastatic disease.
  • Adequate bone marrow reserve and organ function within 7 days before randomization/treatment
  • Minimum life expectancy of 12 weeks.

Key Exclusion Criteria:

  • Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade ≤ 1 or baseline
  • 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 eg, prodromal symptoms
  • Significant cardiac diseases
  • History of non-infectious Interstitial lung disease (ILD)/pneumonitis that required steroids
  • Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period
  • Prior exposure to anticancer therapies without an adequate treatment washout period prior to enrolment
  • Prior treatment with TROP2-directed Anti-drug antibody ADC Antibody-drug conjugate (ADCs), other ADCs with deruxtecan payload
  • Severe hypersensitivity to Dato-DXd monoclonal antibodies polysorbate 80 or other monoclonal antibodies.
  • Pregnant, breastfeeding, planning to become pregnant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05489211


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Show Show 71 study locations
Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo, Inc.
Investigators
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Principal Investigator: Yelena Janjigian, MD Rockefeller Outpatient Pavilion
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05489211    
Other Study ID Numbers: D926UC00001
First Posted: August 5, 2022    Key Record Dates
Last Update Posted: September 19, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the European Federation of Pharmaceutical Industries and Associations (EFPIA) Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
TROPION-PanTumor03
Datopotamab Deruxtecan (Dato-DXd)
Solid Tumours
Antibody-drug conjugate (ADC)
Trophoblast cell surface protein 2 (TROP2)
Additional relevant MeSH terms:
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Endometrial Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Neoplasms, Female
Uterine Neoplasms
Uterine Diseases
Leucovorin
Bevacizumab
Nivolumab
Durvalumab
Carboplatin
Fluorouracil
Capecitabine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Immune Checkpoint Inhibitors
Antidotes
Protective Agents
Vitamin B Complex