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

Phase 2

Recruiting

• Conditions: Part 1: Bladder, Biliary Tract, Cervical, Endometrial, Ovarian, Pancreatic Cancer, Rare Tumors, Any Tumor Type Excluding Breast, Gastric, Colorectal Cancer; Part 2: HER2 Expressing/Amplified Solid Tumors Excluding Breast, Gastric, Colorectal Cancer
• Interventions: Drug: Trastuzumab deruxtecan

• Registration Number: NCT04482309
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-20
• Study First Submitted QC: 2020-07-20
• Study First Posted: 2020-07-22
• Study Start: 2020-08-18
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-20
• Primary Completion: 2027-07-30
• Study Completion: 2027-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 468

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 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.

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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.
• Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer for Part 1. For Part 2, 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1 Cohort 7	Trastuzumab deruxtecan	Rare tumors
Part 1 Cohort 5	Trastuzumab deruxtecan	Ovarian cancer
Part 1 Cohort 6	Trastuzumab deruxtecan	Pancreatic cancer
Part 2 Cohort A	Trastuzumab deruxtecan	Any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer)
Part 2 Cohort C	Trastuzumab deruxtecan	HER2 IHC 2+ or 1+ endometrial cancer
Part 1 Cohort 1	Trastuzumab deruxtecan	Biliary tract cancer
Part 1 Cohort 2	Trastuzumab deruxtecan	Bladder cancer
Part 1 Cohort 3	Trastuzumab deruxtecan	Cervical cancer
Part 1 Cohort 4	Trastuzumab deruxtecan	Endometrial cancer
Part 2 Cohort B	Trastuzumab deruxtecan	Any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer)
Part 2 Cohort E	Trastuzumab deruxtecan	HER2 IHC 2+ or 1+ cervical cancer
Part 2 Cohort D	Trastuzumab deruxtecan	HER2 IHC 2+ or 1+ ovarian cancer

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	An average of approximately 6 months	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
Occurrence of adverse events (AEs) and serious adverse events (SAEs)	An average of approximately 8 months	Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
Duration of response (DoR)	An average of approximately 6 months	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)	An average of approximately 6 months	DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD).
Progression free survival (PFS)	An average of approximately 6 months	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 at 6 and 12 months	Up to 12 months	The proportion of patients alive at 6 and 12 months (Kaplan-Meier estimates).
Overall survival (OS)	An average of approximately 14 months	OS is the time from date of first dose of study treatment until death due to any cause.
Proportion of patients alive and progression-free at 6 months and 12 months	Up to 12 months	The proportion of patients alive and progression-free at 6 and 12 months (Kaplan-Meier estimates).
Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181	An average of approximately 8 months	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	An average of approximately 6 months	Individual participant data and descriptive statistics will be provided for data at each time point.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sutton, United Kingdom