A study to investigate anti-tumor activity and safety of trastuzumab deruxtecan in patients with solid tumors carrying specific HER2 mutations.

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

6 Jul 2021 → ongoing

Decision date (initial)

2024-07-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-516158-22-00

EudraCT number

2020-002368-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacodynamic, Safety, Pharmacogenomic, Pharmacogenetic, Pharmacokinetic

To assess the efficacy of T-DXd in patients with metastatic or unresectable tumors harboring specific HER2 activating mutations across tumor types.

Secondary objectives 4

1. 1. To further assess the efficacy of T-DXd in patients with metastatic or unresectable tumors harboring pre-specified HER2 activating mutations across tumor types.
2. 2. To assess the safety and tolerability of T-DXd.
3. 3. To assess the PK of T-DXd, total anti-HER2 antibody and MAAA-1181a in serum.
4. 4. To investigate the immunogenicity of T-DXd.

Conditions and MedDRA coding

Treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adults ≥18 years old. Other age restrictions may apply as per local regulations.
2. Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations locally determined by NGS on tumor tissue, who have progressed following prior treatment or who have no satisfactory alternative treatment options.
3. Prior HER2 targeted therapy is permitted.
4. All patients must provide an FFPE tumor sample for retrospective central HER2 testing.
5. LVEF ≥50%
6. ECOG 0-1

Exclusion criteria 8

1. HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma.
2. HER2 mutant NSCLC.
3. History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening
4. Lung-specific intercurrent clinically significant severe illnesses.
5. History of active primary immunodeficiency, known HIV, active HBV or HCV infection
6. Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
7. Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
8. Has spinal cord compression or clinically active central nervous system metastases.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Confirmed objective response rate by RECIST v1.1 based on independent central review (ICR).

Secondary endpoints 8

1. 1) Duration of response (DoR) based on ICR assessment.
2. 2) Disease control rate (DCR) based on ICR assessment.
3. 3) Progression free survival (PFS) based on ICR assessment.
4. 4) Confirmed Objective Response Rate (ORR) based on investigator assessment.
5. 5) Overall survival (OS).
6. 6) Occurrence of adverse events (AEs) and serious adverse events (SAEs).
7. 7) Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181.
8. 8) 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

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Third parties 1

Locations

2 EU/EEA countries · 2 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 11 files

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

Application history

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