A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors

Inclusion Criteria:

• 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 thatexpress HER2, excluding the tumors mentioned above, and breast, non-small celllung 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+ (excludingbreast, gastric cancer, and colorectal cancer). Patients with non-small celllung cancer can be included.

• Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+/ISH+ anytumor type (excluding breast, gastric cancer, and colorectal cancer). Patientswith 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 alternativetreatment option.

• Prior HER2 targeting therapy is permitted.

• HER2 expression scored using current ASCO/CAP guidelines for scoring HER2 forgastric 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 eachcohort

• Has measurable target disease assessed by the Investigator based on RECIST version 1.1.

• Has protocol- defined adequate organ function including cardiac, renal and hepaticfunction.

Exclusion Criteria:

• History of non-infectious pneumonitis/ILD that required steroids, current ILD, orwhere suspected ILD that cannot be ruled out by imaging at screening

• Lung-specific intercurrent clinically significant severe illnesses

• Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, orantifungals

• Pleural effusion, ascites or pericardial effusion that requires drainage, peritonealshunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART

• Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.

• Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon orrectum, adenocarcinoma of the gastric body or gastro-esophageal junction, ornon-small cell lung cancer for Part 1. For Part 2, patients with primary diagnosisof adenocarcinoma of the breast, adenocarcinoma of the colon or rectum,adenocarcinoma of the gastric body or gastro-esophageal junction will be excluded.

• Medical conditions that may interfere with the subject's participation in the study.