The study of Trastuzumab Deruxtecan to assess its efficacy, safety and tolerability in Patients with Selected HER2 Expressing Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Dec 2020 → ongoing

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-504721-39-02

EudraCT number

2020-001574-29

ClinicalTrials.gov

NCT04482309

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the efficacy of T-DXd in patients with metastatic or unresectable tumors in selected HER2 expressing tumor types.

Secondary objectives 4

1. To further assess the efficacy of T-DXd in patients with metastatic or unresectable tumors in selected HER2-expressing tumor types (DoR, DCR, PFS and OS)
2. To assess the safety and tolerability of T-DXd
3. To assess the PK of T-DXd, total anti-HER2 antibody and MAAA-1181 in serum
4. To investigate the immunogenicity of T-DXd

Conditions and MedDRA coding

HER2 Expressing Tumors

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002978-PIP02-24

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Locally advanced, unresectable, or metastatic disease based on most recent imaging
2. 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.
3. 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+.
4. Progressed following prior treatment or who have no satisfactory alternative treatment option.
5. Prior HER2 targeting therapy is permitted.
6. 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
7. Has measurable target disease assessed by the Investigator based on RECIST version 1.1.
8. Has protocol-defined adequate organ function including cardiac, renal and hepatic function.

Exclusion criteria 7

1. History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening
2. Lung-specific intercurrent clinically significant severe illnesses
3. Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
4. Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART
5. Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.
6. Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastroesophageal 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.
7. Medical conditions that may interfere with the subject's participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) according to RECIST v1.1, as assessed by investigator

Secondary endpoints 9

1. Based on RECIST 1.1, as assessed by Investigator: 1) Duration of response (DoR).
2. Disease control rate (DCR).
3. Progression free survival (PFS).
4. Proportion of patients alive and progression-free at 3 monthly intervals staring from 6 months.
5. Overall survival (OS).
6. Proportion of patients alive at 3 monthly intervals staring from 6 months
7. Occurrence of adverse events (AEs) and serious adverse events (SAEs).
8. Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181.
9. The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Locations

3 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications