A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)
This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors. This study will consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer. Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.
• Locally advanced, unresectable, or metastatic disease based on most recent imaging.
• Part 1:The respective cohorts for patient inclusion are:
‣ Cohort 1: Biliary tract cancer
⁃ Cohort 2: Bladder cancer
⁃ Cohort 3: Cervical cancer
⁃ Cohort 4: Endometrial cancer
⁃ Cohort 5: Epithelial ovarian cancer
⁃ Cohort 6: Pancreatic cancer
⁃ Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer.
• Part 2:The respective cohorts for patient inclusion are:
‣ Cohort A: Metastatic or advanced solid tumors that are HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included.
⁃ Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+/ISH+ any tumor type (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included.
⁃ Cohort C: Metastatic or advanced solid endometrial cancer that is HER2 IHC 2+ or 1+.
⁃ Cohort D: Metastatic or advanced ovarian cancer that is HER2 IHC 2+ or 1+.
⁃ Cohort E: Metastatic or advanced solid cervical cancer that is HER2 IHC 2+ or 1+.
• Progressed following prior treatment or who have no satisfactory alternative treatment option.
• Prior HER2 targeting therapy is permitted.
• HER2 expression scored using current ASCO/CAP guidelines for scoring HER2 for gastric cancer.
‣ Part 1: IHC 3+ or IHC 2+ by local or central assessment
⁃ Part 2: IHC and ISH results by central assessment as pre-defined for each cohort
• Has measurable target disease assessed by the Investigator based on RECIST version 1.1.
• Has protocol- defined adequate organ function including cardiac, renal and hepatic function.