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)

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.

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.