Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)
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| ClinicalTrials.gov Identifier: NCT05489211 |
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Recruitment Status :
Recruiting
First Posted : August 5, 2022
Last Update Posted : March 9, 2023
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Sponsor:
AstraZeneca
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
AstraZeneca
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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 |
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).
| 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 : | March 31, 2025 |
| Estimated Study Completion Date : | March 31, 2025 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Substudy-1A
Dato-DXd will be evaluated as monotherapy
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a |
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Experimental: Substudy-1B
Dato-Dxd in combination with Durvalumab will be evaluated
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a Drug: Durvalumab Administered as an IV
Other Names:
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Experimental: Substudy-1C
Dato-Dxd in combination with AZD5305 will be evaluated
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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
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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:
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Experimental: Substudy-2A
Dato-DXd in combination with capecitabine will be evaluated
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a Drug: Capecitabine Administered orally
Other Name: Xeloda |
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Experimental: Substudy-2B
Dato-DXd in combination with 5-FU will be evaluated
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a Drug: 5-Fluorouracil Administered as an IV
Other Name: Adrucil |
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Experimental: Substudy-2C
Dato-DXd in combination with chemotherapy (capecitabine or 5-FU) + nivolumab will be evaluated
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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 |
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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
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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 |
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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 :
- 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.
- 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 :
- 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.
- 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.
- 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.
- 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.
- 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
- 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).
- 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).
- 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.
- 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
- 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
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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
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 92 study locations
Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo, Inc.
Investigators
| Principal Investigator: | Yelena Janjigian, MD | Rockefeller Outpatient Pavilion |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT05489211 |
| Other Study ID Numbers: |
D926UC00001 |
| First Posted: | August 5, 2022 Key Record Dates |
| Last Update Posted: | March 9, 2023 |
| Last Verified: | March 2023 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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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 |