A Phase II Study of T-DXd in Patients with Selected HER2-expressing Tumors

Recruiting

Recruitment & Eligibility

Inclusion Criteria

Locally advanced, unresectable, or metastatic disease based on most recent imaging.

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.
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.

Exclusion Criteria

History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where 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, or antifungals
Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART
Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.
Patients with primary diagnosis of 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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)		Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)		PFS is the time from date of first dose of study treatment until the date of objective disease progression or death.
Proportion of patients alive and progression-free at 6 months and 12 months	6 and 12 months	The proportion of patients alive and progression-free at 6 and 12 months (Kaplan-Meier estimates).
Proportion of patients alive at 6 and 12 months	6 and 12 months	The proportion of patients alive at 6 and 12 months (Kaplan-Meier estimates).
Overall survival (OS)		OS is the time from date of first dose of study treatment until death due to any cause.
Duration of response (DoR)		DOR is defined as the time from the date of first documented response until the date of documented progression or death.
Disease control rate (DCR)		DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD).
Occurrence of adverse events (AEs) and serious adverse events (SAEs)		Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181		Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a
The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd		Individual participant data and descriptive statistics will be provided for data at each time point.