A Study of Dato-DXd in Chinese Patients With Advanced Non-Small Cell Lung Cancer, Triple-negative Breast Cancer and Other Solid Tumors (TROPION-PanTumor02)

Phase 2Active Not RecruitingNCT05460273

AstraZeneca119 enrolled

Overview

Researchers are looking for a better way to treat advanced Triple-Negative Breast Cancer (TNBC) and Non-Small-Cell Lung Cancer (NSCLC). "Advanced" usually means that the cancer keeps growing even with treatment. The cancer may also be "metastatic", which means that it has spread to other parts of the body or the surrounding tissue. The study drug, Datopotamab deruxtecan, is designed to work by attaching to the tumor cells and stopping the tumor growth. Datopotamab deruxtecan is also known as Dato-DXd. In this study, the researchers want to find out how well Dato-DXd works to stop tumors from growing in Chinese participants with NCSLC or TNBC. This is the first time Dato-DXd is being studied in Chinese population. Participants in this study will get Dato-DXd through a needle as an injection. They will get 1 dose of Dato-DXd every 3 weeks until their cancer gets worse or they leave the study for another reason. Participants will visit their study sites at least once every 3 weeks for as long as they are in the study. The study doctors will take blood samples every 3 weeks and take images of the participants' tumors every 6 weeks until the participant leaves the study.

This is a Phase 1/Phase 2, multicentre, open-label, multiple-cohort study, which is designed to evaluate the efficacy, safety, Pharmacokinetic, and immunogenicity of Dato-DXd in adult Chinese participants with advanced or metastatic solid tumours. It is a single-arm study with no blinding. This study is divided into different cohorts. Participants of the same cohort are with the same tumour type. The starting cohorts are Cohort 1 (NSCLC) and Cohort 2 (TNBC). Future cohorts will consist of other advanced or metastatic solid tumour types, including, but not limited to, advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma or urothelial carcinoma that is refractory or intolerant to SoC therapy or for which no Standard of Care therapy is available. Cohort 1 and Cohort 2 will be prioritised for immediate enrolment and the protocol will be amended as needed for the future cohorts. Cohort 1: The target population of Cohort 1 is adult Chinese participants with advanced or metastatic NSCLC with or without actionable genomic alterations(AGAs) (ie, alterations in genes with approved therapies, such as EGFR, ALK, or other known AGAs). Eligible participants without AGAs will have been previously treated with platinum-based chemotherapy and anti-PD-1/anti-PD-L1 monoclonal antibody either in combination or sequentially. Participants without AGAs who received anti-PD-1/anti-PD-L1 monoclonal antibody as frontline therapy may have received the combination of platinum-based chemotherapy and anti-PD-1/anti-PD-L1 monoclonal antibody in the second-line setting. Eligible participants with AGAs will have been previously treated with one or two prior lines of applicable targeted therapy that is approved for the participant's genomic alteration and platinum-based chemotherapy as the only prior line of cytotoxic therapy. Participants with AGAs may have received up to one anti-PD-1/anti-PD-L1 monoclonal antibody treatment alone or in combination with chemotherapy. A total of approximately 40 eligible participants in China will be enrolled in this cohort, including approximately 6 participants with AGAs. Cohort 2: The target population of Cohort 2 is adult Chinese participants with inoperable locally advanced or metastatic TNBC who have received at least 2 prior chemotherapy regimens for advanced breast cancer, counting the (neo)adjuvant therapy as a prior chemotherapy regimen if progression occurred within 12 months after completion of the therapy (DFI ≤ 12 months). A total of approximately 78 eligible participants in China will be enrolled in this cohort. Cohort 2 will enroll at most around 20% (approximately N=15) of enrolled participants with a DFI ≤ 12 months. Enrolled participants will be treated with Dato-DXd at 6.0 mg/kg via an IV infusion on Day 1,every 3 weeks. The primary objective of the study is to estimate the effectiveness of Dato-DXd by assessment of confirmed ORR by independent central review.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Capable of giving signed informed consent. * Participant must be ≥ 18 years at the time of screening. * Eastern Cooperative Oncology Group performance status of 0 or 1. * At least one lesion not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline and can be accurately measured at baseline and is suitable for accurate repeated measurements. Additional Inclusion Criteria for Cohort 1 (NSCLC): \- Histologically or cytologically documented Stage IIIB or IIIC NSCLC disease not amenable for surgical resection or definitive chemoradiation or Stage IV NSCLC disease at the beginning of study intervention. For the subset of participants without AGAs: * Documented negative test results for EGFR and ALK genomic alterations. If test results for EGFR and ALK are not available, participants are required to undergo testing performed locally for these genomic alterations. * Participants must meet one of the required prior therapy requirements for advanced or metastatic NSCLC. For the subset of participants with AGAs: \- Documented positive test results for one or more actionable genomic alteration: EGFR, ALK, ROS1, METex14 skipping, RET or other AGAs with approved therapies \- Received one or two prior lines of applicable targeted therapy for the participant's genomic alteration at the time of screening. Additional Inclusion Criteria for Cohort 2 (TNBC) * Pathologically documented oestrogen and progesterone receptor-negative and HER2-negative expression. * Inoperable locally advanced or metastatic breast cancer. * Received at least 2 prior chemotherapy regimens for locally advanced or metastatic breast cancer and previously treated with a taxane in any setting. Key Exclusion Criteria: * Has leptomeningeal carcinomatosis or metastasis * Has clinically significant corneal disease * Has known active hepatitis or uncontrolled hepatitis B or C infection * Has a history of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Prior exposure to specific therapies without an adequate treatment washout period prior to enrolment. Additional Exclusion Criteria for Cohort 1 (NSCLC): \- Has mixed SCLC and NSCLC histology.

Locations (21)

Research Site

Beijing, China

Research Site

Beijing, China

Research Site

Beijing, China

Research Site

Bengbu, China

Research Site

Changchun, China

Research Site

Changchun, China

Research Site

Chengdu, China

Research Site

Chongqing, China

Research Site

Dalian, China

Research Site

Fuzhou, China

...and 11 more locations

Outcomes

Primary Outcomes

Confirmed Objective Response Rate(ORR) Assessed by Independent Central Review(ICR)

Confirmed ORR is defined as the proportion of participants in each cohort who have a confirmed CR or confirmed PR, as assessed by ICR per RECIST 1.1.

Time frame: TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.

Secondary Outcomes

Confirmed Objective Response Rate(ORR) Assessed by Investigator

Confirmed ORR is defined as the proportion of participants in each cohort who have a confirmed CR or confirmed PR, as determined by investigator assessment per RECIST 1.1.

Duration of Response (DoR), Assessed by Investigator

Duration of response is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression per RECIST 1.1, as assessed by investgator, or death due to any cause.

Disease Control Rate (DCR), Assessed by ICR

Disease control rate is defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST 1.1, as assessed by ICR

Best Overall Response (BoR) , Assessed by ICR

Best overall response is defined as participant's best confirmed response during their participation in the study, but prior to starting any subsequent anticancer therapy, up until RECIST 1.1-defined PD or the last evaluable assessment in the absence of RECIST 1.1-defined progression.

Time To Response (TTR) , Assessed by ICR

Time to response is defined as the time from the date of the first dose of study intervention until the date of first documented objective response, which is subsequently confirmed per RECIST 1.1

Progression-Free Survival (PFS) , Assessed by ICR

Progression-free survival is defined as time from the date of the first dose of study intervention until progression per RECIST 1.1, as assessed by ICR, or death due to any cause.

Overall Survival (OS)

Overall survival is defined as the time from the date of the first dose of study intervention to the date of death due to any cause.

Progression-Free Survival (PFS) , Assessed by Investigator

Progression-free survival is defined as time from the date of the first dose of study intervention until progression per RECIST 1.1, as assessed by investigator, or death due to any cause.

Disease Control Rate (DCR), Assessed by Investigator

Best Overall Response (BoR) , Assessed by Investigator

Time To Response (TTR) , Assessed by Investigator

Time to response is defined as the time from the date of the first dose of study intervention until the date of first documented objective response, which is subsequently confirmed per RECIST 1.1.

Pharmacokinetic Parameter: Area Under the Plasma Concentration- Time Curve (AUC) _ Total Anti-TROP2 Antibody

PK parameters of Total Anti-TROP2 Antibody\_Area under the curve

Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) _ Total Anti-TROP2 Antibody

PK parameters of Total Anti-TROP2 Antibody\_Maximum observed concentration

Pharmacokinetic Parameter: Area Under the Plasma Concentration- Time Curve (AUC) _Dato-DXd

PK parameters of Dato-DXd\_Area under the curve

Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) _ Dato-DXd

PK parameters of Dato-DXd\_Maximum observed concentration

Pharmacokinetic Parameter: Area Under the Plasma Concentration- Time Curve (AUC) _ MAAA-1181a

PK parameters of MAAA-1181a\_Area under the curve

Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) _ MAAA-1181a

PK parameters of MAAA-1181a\_Maximum observed concentration

Pharmacokinetic Parameter: Time to Maximum Plasma Concentration (Tmax) _Total Anti-TROP2 Antibody

PK parameters of Total Anti-TROP2 Antibody\_Time to maximum plasma concentration

Pharmacokinetic Parameter: Time to Maximum Plasma Concentration (Tmax) _Dato-DXd

Time to maximum plasma concentration

Pharmacokinetic Parameter: Time to Maximum Plasma Concentration (Tmax) _ MAAA-1181a

PK parameters of MAAA-1181a\_Time to maximum plasma concentration

Immunogenicity of Dato-DXd

The prevalence of ADA (positive at any visit)

Duration of Response (DoR), Assessed by ICR

A Study of Dato-DXd in Chinese Patients With Advanced Non-Small Cell Lung Cancer, Triple-negative Breast Cancer and Other Solid Tumors (TROPION-PanTumor02)

Overview

Conditions

Interventions

Eligibility

Locations (21)

Outcomes

Primary Outcomes

Secondary Outcomes