Phase 1b Study of Dato-DXd in Combination with Immunotherapy with or without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer

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

21 Oct 2022 → ongoing

Decision date (initial)

2024-06-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-505992-54-00

EudraCT number

2021-000274-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others, Efficacy, Pharmacodynamic, Therapy

To assess the safety and tolerability of combination treatment with Dato-DXd and immunotherapy, with or without up to 4 cycles of carboplatin

Secondary objectives 3

1. To assess the efficacy of combination treatment with Dato-DXd and immunotherapy, with or without up to 4 cycles of carboplatin
2. To evaluate the PK of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789, with or without up to 4 cycles of carboplatin
3. To assess the immunogenicity of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 with or without up to 4 cycles of carboplatin

Conditions and MedDRA coding

Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant ≥18 years old on the day of signing the ICF (local regulatory requirement to consent should be followed)
2. Histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC, without EGFR or ALK genomic alterations (not required for squamous histology) and no known genomic alterations in other actionable driver kinases with approved therapies (KRAS mutations eligible). Cohort 4a will enroll participants with squamous histology only; cohorts 5 Part 2A and Part 2B as well as Cohorts 12 and 13 will enroll participants with non-squamous histology only
3. For Cohorts 1 to 4, participants must be treatment-naïve or have received and radiologically progressed after only 1 prior line of systemic chemotherapy, without concomitant immune checkpoint inhibitors for advanced or metastatic NSCLC. Cohorts 4a, 5 to 11 and 14 participants must be treatment-naïve for advanced or metastatic NSCLC. For Cohorts 12 & 13, participants must be CPI-acquired resistant after 1 or 2 prior lines of systemic therapy for advanced or metastatic NSCLC, of which at least 1 prior line of therapy should contain an approved anti-PD-1/PD-L1
4. Willing and able to undergo a mandatory tumor biopsy. A tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen may be substituted for the biopsy collected during screening. For Cohorts 12 and 13, a tumor sample taken ≤24 months prior to screening is acceptable.
5. Has measurable disease per RECIST1.1 within 28 days prior to Cycle 1 Day 1
6. Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 at screening
7. Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 day 1
8. For Cohorts 5 to 14 only: Documented IHC PD-L1 expression per analytically validated Ventana PD-L1 (SP263) IHC assay, 22C3 PharmDx assay, or 28-8 PharmDx assay

Exclusion criteria 9

1. Active or prior documented autoimmune or inflammatory disorders
2. Uncontrolled or significant cardiac disease
3. History of another primary malignancy with exceptions
4. active or uncontrolled hepatitis B or C virus or uncontrolled HIV infection
5. spinal cord compression or clinically active CNS metastases
6. History of (non-infectious) ILD/pneumonitis, including radiation pneumonitis, that required steroids
7. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illness
8. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
9. Clinically significant corneal disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability of combination treatment with Dato-DXd and immunotherapy with or without up to 4 cycles of carboplatin, as measured by DLTs, TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings

Secondary endpoints 3

1. Efficacy of combination treatment with Dato-DXd and immunotherapy, with or without up to 4 cycles of carboplatin as measured by ORR, DoR, DCR, PFS, TTR, Best percentage change in the SoD of measurable tumors and OS
2. PK of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789, with or without up to 4 cycles of carboplatin as assessed by plasma concentrations and PK parameters of Dato-Dxd, total anti-TROP2 antibody and DXd (MAAA-1181a). Serum concentrations and PK parameters of durvalumab, AZD2936, MEDI5752 and AZD7789
3. Immunogenicity of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 with or without 4 cycles of carboplatin as assessed by the prevalence and incidence of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA.

Investigational products

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

Test 6

Comparator 1

Auxiliary 2

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

Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

Clinical Study Information Center

Locations

4 EU/EEA countries · 17 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 45 files

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

Application history

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