Clinical trial NCT05489211: Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Endometrial Cancer
Gastric Cancer
Metastatic Castration-resistant Prostate Cancer
Ovarian Cancer
Colorectal Cancer
Urothelial Cancer
Biliary Tract Cancer
Keywords: TROPION-PanTumor03
Datopotamab Deruxtecan (Dato-DXd)
Solid Tumours
Antibody-drug conjugate (ADC)
Trophoblast cell surface protein 2 (TROP2)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2022-08-05
Enrollment: 582
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Within each substudy, Dato-DXd will be evaluated as monotherapy (all except #2 Gastric Cancer) and in combination with approved or novel anticancer agents that may be active in the tumour type being evaluated (all except #1 Endometrial Cancer and #7 Biliary Tract Cancer). All substudies will be treatment assigned.

Substudy 1 (Endometrial): MONO: Dato-DXd

Substudy 2 (Gastric): COMBO: Dato-DXd + capecitabine, Dato-DXd + 5-FU

Substudy 3 (mCRPC): MONO: Dato-DXd; COMBO: Dato-DXd + prednisone/prednisolone

Substudy 4 (Ovarian): MONO: Dato-DXd; COMBO: Dato-DXd + carboplatin + bevacizumab --\> Dato-DXd + bevacizumab

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

Substudy 6 (Urothelial): MONO: Dato-DXd; COMBO: Dato-DXd + volrustomig, Dato-DXd + rilvegostomig, Dato-DXd + carboplatin or cisplatin

Substudy 7 (BTC): MONO: Dato-DXd
Primary purpose: TREATMENT

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), 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).

Eligibility criteria: 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
* Irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator, for example hearing loss
* 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
* Known active tuberculosis infection
* Mean resting corrected QTcF \> 470 ms
* In the judgement of the investigator, history of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause TdP
* In the judgement of the investigator, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives
* Uncontrolled or 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
* Palliative radiotherapy with a limited field of radiation within ≤ 2 weeks or to more than 30% of the bone marrow within ≤ 4 weeks before the first dose of study intervention
* 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 therapies or other antibody-drug conjugate (ADCs) with deruxtecan payload
* Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention
* Previous treatment in the present study
* Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to first dose of study intervention or concurrent enrolment in another clinical study
* Severe hypersensitivity to Dato-DXd or any of the excipients, including but not limited to polysorbate 80 or other monoclonal antibodies
* Involvement in the planning and/or conduct of the study
* Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements
* Females that are pregnant, breastfeeding, or planning to become pregnant
* Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of Dato-DXd

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: From baseline to progressive disease or death (approximately 1 year)
measure: The number of subjects with adverse events/serious adverse events
timeFrame: 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)
measure: PSA50 response (Substudy 3 only)
timeFrame: From baseline to PSA response evaluated according to the PCWG3 criteria (up to 12 weeks)
measure: Progression free survival (PFS) response (Substudy 4C only)
timeFrame: From baseline to progressive disease or death (approximately 1 year)
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: From baseline to progressive disease or death (approximately 1 year)
measure: Duration Of Response (DoR)
timeFrame: From baseline to progressive disease or death (approximately 1 year)
measure: Disease Control Rate (DCR)
timeFrame: At 12 and 14 weeks
measure: Best percentage change in tumour size
timeFrame: From baseline to progressive disease or death (approximately 1 year)
measure: Pharmacokinetics of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): Maximum plasma concentration of the drug (Cmax)
timeFrame: At predefined intervals throughout the treatment period (approximately 1 year)
measure: Pharmacokinetics of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): The time taken to reach the maximum concentration (Tmax)
timeFrame: At predefined intervals throughout the treatment period (approximately 1 year)
measure: Pharmacokinetic Parameter of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): Area under the plasma concentration- time curve (AUC)
timeFrame: At predefined intervals throughout the treatment period (approximately 1 year)
measure: Plasma concentration of Total anti-TROP2 antibody
timeFrame: Throughout the treatment period at pre-defined intervals (approximately 1 year)
measure: Plasma concentration of MAAA-1181a
timeFrame: Throughout the treatment period at pre-defined intervals (approximately 1 year)
measure: Anti Drug Antibody (ADA) for Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6)
timeFrame: Throughout the treatment period at pre-defined intervals and including the safety follow-up period (approximately 1 year)
measure: Radiographic PFS (Substudy 3)
timeFrame: From baseline to radiographic progression or death (approximately 1 year)
measure: PSA progression (Substudy 3)
timeFrame: From baseline to PSA response evaluated according to the PCWG3 criteria (up to 12 weeks)
measure: CA-125 response (Substudy 4)
timeFrame: From baseline to CA-125 response evaluated according to the GCIG criteria (up to 12 weeks)
measure: Overall survival (OS) (Substudy 4)
timeFrame: From baseline to death (approximately 1 year)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Muncie
country: United States
facility: Research Site
state: Indiana
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: East Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Commack
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
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state: Oregon
city: Nashville
country: United States
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state: Tennessee
city: Nashville
country: United States
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state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Madison
country: United States
facility: Research Site
state: Wisconsin
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Suresnes
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Shinagawa-ku
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Gliwice
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Bellinzona
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Liou Ying Township
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Kadıkoy/Istanbul
country: Turkey
facility: Research Site
city: Karsiyaka
country: Turkey
facility: Research Site
city: Konya
country: Turkey
facility: Research Site
city: Pamukkale
country: Turkey
facility: Research Site
city: Samsun
country: Turkey
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Global Clinical Lead, MD
role: PRINCIPAL_INVESTIGATOR
References: