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History of Changes for Study: NCT05489211
Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours
Latest version (submitted April 24, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 3, 2022 None (earliest Version on record)
2 September 16, 2022 Recruitment Status, Study Status, Contacts/Locations, Study Design and Oversight
3 January 13, 2023 Contacts/Locations, Study Status and Study Identification
4 February 8, 2023 Contacts/Locations and Study Status
5 March 8, 2023 Contacts/Locations and Study Status
6 August 24, 2023 Contacts/Locations, Arms and Interventions, Outcome Measures, Study Design, IPDSharing, Study Status, Study Identification, Eligibility, Conditions and Study Description
7 October 31, 2023 Contacts/Locations and Study Status
8 December 7, 2023 Contacts/Locations and Study Status
9 January 19, 2024 Arms and Interventions, Study Status and Study Design
10 February 27, 2024 Contacts/Locations and Study Status
11 April 24, 2024 Contacts/Locations, Study Status and Study Design
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Study NCT05489211
Submitted Date:  August 3, 2022 (v1)
Open or close this module Study Identification
Unique Protocol ID: D926UC00001
Brief Title: Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours
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)
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2022
Overall Status: Not yet recruiting
Study Start: August 3, 2022
Primary Completion: June 2, 2025 [Anticipated]
Study Completion: June 2, 2025 [Anticipated]
First Submitted: July 21, 2022
First Submitted that
Met QC Criteria:		 August 3, 2022
First Posted: August 5, 2022 [Actual]
Last Update Submitted that
Met QC Criteria:		 August 3, 2022
Last Update Posted: August 5, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: AstraZeneca
Responsible Party: Sponsor
Collaborators: Daiichi Sankyo
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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.
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).
Open or close this module Conditions
Conditions: Endometrial Cancer
Gastric Cancer
Metastatic Castration-resistant Prostate Cancer
Ovarian Cancer
Colorectal Cancer
Keywords: TROPION-PanTumor03
Datopotamab Deruxtecan (Dato-DXd)
Solid Tumours
Antibody-drug conjugate (ADC)
Trophoblast cell surface protein 2 (TROP2)
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment

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
Number of Arms: 13
Masking: None (Open Label)
Allocation: N/A
Enrollment: 451 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Substudy-1A
Dato-DXd will be evaluated as monotherapy
 Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • DS-1062a
Drug: Capecitabine
Administered orally
Other Names:
  • 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 Names:
  • DS-1062a
Drug: 5-Fluorouracil
Administered as an IV
Other Names:
  • 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 Names:
  • DS-1062a
Drug: Capecitabine
Administered orally
Other Names:
  • Xeloda
Drug: 5-Fluorouracil
Administered as an IV
Other Names:
  • Adrucil
Drug: Nivolumab
Administered as an IV
Other Names:
  • OPDIVO
Experimental: Substudy-3A
Dato-DXd will be evaluated as monotherapy
 Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • DS-1062a
Drug: AZD5305
Oral poly ADP ribose polymerase (PARP) inhibitor
Drug: Carboplatin
Administered as an IV
Other Names:
  • Paraplatin
Experimental: Substudy-5A
Dato-DXd will be evaluated as monotherapy
 Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Names:
  • 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 Names:
  • DS-1062a
Drug: Capecitabine
Administered orally
Other Names:
  • Xeloda
Drug: 5-Fluorouracil
Administered as an IV
Other Names:
  • Adrucil
Drug: Leucovorin LV
Administered as an IV
Other Names:
  • Folinic acid
Drug: Bevacizumab
Administered as an IV
Other Names:
  • Avastin
Open or close this module Outcome Measures
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).
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 130 Years
Sex: All
Gender Based:
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.
Open or close this module Contacts/Locations
Central Contact Person: AstraZeneca Clinical Study Information Center
Telephone: 1-877-240-9479
Email: information.center@astrazeneca.com
Study Officials: Yelena Janjigian, MD
Principal Investigator
Rockefeller Outpatient Pavilion
Locations: United States, California
Research Site
Los Angeles, California, United States, 90095
Research Site
San Diego, California, United States, 92103
Research Site
Santa Rosa, California, United States, 92805
United States, Indiana
Research Site
Indianapolis, Indiana, United States, 46202
United States, Kansas
Research Site
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02114
United States, New Mexico
Research Site
Albuquerque, New Mexico, United States, 87109
United States, Ohio
Research Site
Cincinnati, Ohio, United States, 45219
Research Site
Columbus, Ohio, United States, 43219
United States, Oregon
Research Site
Portland, Oregon, United States, 97239
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37203
Research Site
Nashville, Tennessee, United States, 37232
United States, Texas
Research Site
Houston, Texas, United States, 77030
Canada, Ontario
Research Site
Toronto, Ontario, Canada, M4N 3M5
Research Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H2X 3J4
Research Site
Montreal, Quebec, Canada, H3G 1A4
France
Research Site
Bordeaux, France, 33076
Research Site
Lyon, France, 69373
Research Site
Marseille, France, 13273
Research Site
Suresnes, France, 92150
Germany
Research Site
Berlin, Germany, 10117
Research Site
Essen, Germany, 45136
Research Site
Hannover, Germany, 30625
Research Site
München, Germany, 81377
Research Site
Regensburg, Germany, 93053
Italy
Research Site
Firenze, Italy, 50139
Research Site
Genova, Italy, 16132
Research Site
Milan, Italy, 20141
Research Site
Milano, Italy, 20132
Research Site
Milano, Italy, 20162
Research Site
Napoli, Italy, 80131
Research Site
Rome, Italy, 00168
Korea, Republic of
Research Site
Seodaemun-gu, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 06351
Research Site
Seoul, Korea, Republic of, 5505
Poland
Research Site
Kraków, Poland, 30-688
Research Site
Poznań, Poland, 61-866
Research Site
Warszawa, Poland, 02-781
Switzerland
Research Site
Basel, Switzerland, 4031
Research Site
Bellinzona, Switzerland, 6500
Research Site
St. Gallen, Switzerland, 9007
Taiwan
Research Site
Liou Ying Township, Taiwan, 736
Research Site
Taipei, Taiwan, 100
Research Site
Taipei, Taiwan, 11259
Research Site
Taipei, Taiwan, 112
Research Site
Taoyuan, Taiwan, 333
Turkey
Research Site
Samsun, Turkey
United Kingdom
Research Site
Cambridge, United Kingdom, CB2 0QQ
Research Site
Dundee, United Kingdom, DD1 9SY
Research Site
London, United Kingdom, NW1 2PG
Research Site
London, United Kingdom, SE1 9RT
Open or close this module IPDSharing
Plan to Share IPD: Yes
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 Information:
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
Open or close this module References
Citations:
Links:
Available IPD/Information:
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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services