Study of Dato-DXd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Препарат Datopotamab deruxtecan (Dato-DXd)
  Intravenous (IV) Antibody drug conjugate
• Препарат Capecitabine
  Administered orally
• Препарат 5-Fluorouracil
  Administered as an IV
• Препарат Volrustomig
  Administered as an IV
• Препарат Carboplatin
  Administered as an IV
• Препарат Bevacizumab
  Administered as an IV
• Препарат Rilvegostomig
  Administered as an IV
• Препарат Prednisone/ prednisolone
  Administered orally
• Препарат Cisplatin
  Administered as an IV

Первичные конечные точки

• Objective response rate (ORR) [Срок оценки: From baseline to progressive disease or death (approximately 1 year)]
• The number of subjects with adverse events/serious adverse events [Срок оценки: 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) [Срок оценки: From baseline to PSA response evaluated according to the PCWG3 criteria (approximately 1 year)]
• Progression free survival (PFS) response (Substudy 4C only) [Срок оценки: From baseline to progressive disease or death (approximately 1 year)]

Вторичные конечные точки (12)

• Progression free survival (PFS) [Срок оценки: From baseline to progressive disease or death (approximately 1 year)]
• Duration Of Response (DoR) [Срок оценки: From baseline to progressive disease or death (approximately 1 year)]
• Disease Control Rate (DCR) [Срок оценки: At approximately 1 year]
• Best percentage change in tumour size [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: At predefined intervals throughout the treatment period (approximately 1 year)]
• Plasma concentration of Total anti-TROP2 antibody [Срок оценки: Throughout the treatment period at pre-defined intervals (approximately 1 year)]
• Plasma concentration of MAAA-1181a [Срок оценки: 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) [Срок оценки: Throughout the treatment period at pre-defined intervals and including the safety follow-up period (approximately 1 year)]
• Radiographic PFS (Substudy 3) [Срок оценки: From baseline to radiographic progression or death (approximately 1 year)]
• PSA progression (Substudy 3) [Срок оценки: From baseline to PSA response evaluated according to the PCWG3 criteria (approximately 1 year)]

Критерии участия

Key Inclusion Criteria: There are additional substudy requirements not reflected here. This list is based solely on the master CSP

• 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

Критерии исключения

• 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, including radiation 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 18 центров

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Идентификаторы

NCT: NCT05489211 · D926UC00001 · 2023-509436-26-00 · 2022-000776-19

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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