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)

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05460273

Collaborator

Daiichi Sankyo, Inc. (Industry)

118

Enrollment

Locations

Arm

23.4

Anticipated Duration (Months)

4.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung Triple Negative Breast Cancer	Drug: Datopotamab Deruxtecan (Dato-DXd)	Phase 1/Phase 2

Detailed Description

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 cohorts of participants 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 without actionable genomic alterations (ie, alterations in genes with approved therapies, such as EGFR, ALK, or other known actionable driver oncogenes).Eligible participants will have been previously treated with platinum-based chemotherapy and anti-PD-1/anti-PD-L1 monoclonal antibody either in combination or sequentially. Participants 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. A total of approximately 40 eligible participants in China will be enrolled in this cohort.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

118 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a Phase 1/Phase 2, multicentre, open-label, multiple-cohort study, which is designed to evaluate the efficacy, safety, PK, and immunogenicity of Dato-DXd in adult Chinese participants with advanced or metastatic solid tumours.This is a Phase 1/Phase 2, multicentre, open-label, multiple-cohort study, which is designed to evaluate the efficacy, safety, PK, and immunogenicity of Dato-DXd in adult Chinese participants with advanced or metastatic solid tumours.

Masking:

None (Open Label)

Masking Description:

It is a single-arm, multi-cohort study with no blinding.

Primary Purpose:

Treatment

Official Title:

Phase 1/2, Multicentre, Open-label, Multiple-cohort Study of Dato-DXd in Chinese Patients With Advanced Non-small-cell Lung Cancer, Triple-negative Breast Cancer, Gastric/Gastroesophageal Junction Cancer, Urothelial Cancer, and Other Solid Tumours (TROPION-PanTumor02)

Actual Study Start Date :

Jul 11, 2022

Anticipated Primary Completion Date :

Dec 20, 2023

Anticipated Study Completion Date :

Jun 23, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dato-DXd Arm This single-arm study consists of multiple cohorts, divided by indication.	Drug: Datopotamab Deruxtecan (Dato-DXd) Dato-DXd is an antibody-drug conjugate (ADC) that binds to TROP2. Other Names: DS-1062a

Arm

Intervention/Treatment

Experimental: Dato-DXd Arm

This single-arm study consists of multiple cohorts, divided by indication.

Drug: Datopotamab Deruxtecan (Dato-DXd)

Dato-DXd is an antibody-drug conjugate (ADC) that binds to TROP2.

Other Names:

DS-1062a

Outcome Measures

Primary Outcome Measures

Confirmed Objective Response Rate(ORR) assessed by independent central review(ICR). [Up to approximately 36 months]
Confirmed ORR assessed by ICR is defined as the proportion of participants in each cohort who have a confirmed complete response(CR) or confirmed partial response(PR), as assessed by ICR per RECIST 1.1. The measure of interest is the estimate of confirmed ORR.

Secondary Outcome Measures

Confirmed Objective Response Rate(ORR) assessed by investigator [Up to approximately 36months]
Confirmed ORR assessed by investigator 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) [Up to approximately 36 months]
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 ICR and by investigator, or death due to any cause.
Disease Control Rate (DCR) [Up to approximately 36 months]
Disease control rate is defined as the percentage of participants who have a confirmed CR or PR or who have stable disease (SD) per RECIST 1.1, as assessed by ICR and by investigator.
Best Overall Response (BoR) [Up to approximately 36 months]
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. Best overall response will be assessed by ICR and by investigator per RECIST 1.1.
Time To Response (TTR) [Up to approximately 36 months]
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, as assessed by ICR and by investigator.
Progression-Free Survival (PFS) [Up to approximately 36 months]
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 and by investigator, or death due to any cause.
Overall Survival (OS) [Up to approximately 36 months]
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.
Number of participants with treatment-emergent adverse event(TEAE), adverse event of special interest (AESI) as assessed by CTCAE version 5.0 [Up to approximately 36 months]
Evaluated from first dose to safety follow up visit.
Pharmacokinetic Parameter: Time to maximum plasma concentration (Tmax) [Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2 Day 1:predose Cycle 4 and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days)]
Immunogenicity of Dato-DXd [Up to approximately 36 months]
The presence of ADAs against Dato-DXd will be evaluated. Titre and neutralising antibodies will be determined when ADA is positive.
Pharmacokinetic Parameter: Area under the plasma concentration- time curve (AUC) [Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2 Day 1 predose; Cycle 4 and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days)]
Pharmacokinetic Parameter: Maximum plasma concentration (Cmax) [Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2 Day 1:predose Cycle 4 and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days)]
Percentage of participants with TEAEs, AESIs as assessed by CTCAE version 5.0 [Up to approximately 36 months]
Evaluated from first dose to safety follow up visit.

Other Outcome Measures

TROP Protein Expression Level [Tumor samples collected before first dose of study intervention]
Expression of TROP2 will be measured in tumour samples.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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.

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Beijing	China	100039
2	Research Site	Beijing	China	100039
3	Research Site	Beijing	China	100044
4	Research Site	Beijing	China	100142
5	Research Site	Bengbu	China	233060
6	Research Site	Changchun	China	130012
7	Research Site	Changchun	China	130021
8	Research Site	Changchun	China	130021
9	Research Site	Chengdu	China	610000
10	Research Site	Chongqing	China	400030
11	Research Site	Dalian	China	116023
12	Research Site	Fuzhou	China	350001
13	Research Site	Guangzhou	China	510060
14	Research Site	Guangzhou	China	510100
15	Research Site	Guangzhou	China	510100
16	Research Site	Hangzhou	China	310022
17	Research Site	Harbin	China	150081
18	Research Site	Jinan	China	250030
19	Research Site	Jinan	China	2501117
20	Research Site	Nanchang	China	330006
21	Research Site	Nanchang	China	330009
22	Research Site	Qingdao	China	110016
23	Research Site	Shanghai	China	201199
24	Research Site	Shenyang	China	110016
25	Research Site	Shenyang	China	110042
26	Research Site	Urumqi	China	830000
27	Research Site	Wuhan	China	430022
28	Research Site	Wuhan	China	430030