Phase II umbrella study of novel anti-cancer agents in patients with NSCLC who progressed on an anti-PD-1/PD-L1 containing therapy.

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

20 Feb 2018 → ongoing

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-509004-15-00

EudraCT number

2017-002208-28

ClinicalTrials.gov

NCT03334617

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Therapy, Safety

To obtain an assessment of the efficacy of each treatment by evaluation of objective response rate.

Secondary objectives 1

1. To assess the efficacy of each therapy by evaluation of tumour response (Disease control rate, Best percentage change in tumour size, Duration of response, Progression free survival) and Overall Survival.

Conditions and MedDRA coding

Patients with non-small cell lung cancer (NSCLC).

Study design 6 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. At least 18 years of age at the time of signing the informed consent form.
2. Patient must have histologically or cytologically confirmed metastatic or locally advanced and recurrent NSCLC which is progressing.
3. Patients eligible for second- or later-line therapy, who must have received an anti PD 1/PD-L1 containing therapy and a platinum-doublet regimen for locally advanced or metastatic NSCLC either separately or in combination. Prior durvalumab is acceptable. The patient must have had disease progression on a prior line of anti PD 1/PD-L1 therapy.
4. Suitable for a new tumour biopsy. For Module 10 and Module 11 only: If in agreement with the sponsor study physician, a patient may be exempt from a biopsy at pre-screening if a tumour tissue sample is obtained after progression on prior anti-PD-(L)1 therapy and ≤ 3 months prior to pre-screening; a tumour sample taken within the previous 24 months is acceptable if no such sample is available.
5. ECOG/WHO performance status of 0 to 1, and a minimum life expectancy of 12 weeks.
6. Patient must have at least 1 lesion that can be accurately measured. A previously irradiated lesion can be considered a target lesion if the lesion has clearly progressed.
7. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.

Exclusion criteria 8

1. Patients whose tumour samples have targetable alterations in EGFR and/or ALK at initial diagnosis are excluded. In addition, patients whose tumour samples are known to have targetable alterations in ROS1, BRAF, MET or RET, are to be excluded.
2. Active or prior documented autoimmune or inflammatory disorders.
3. Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
4. Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control.
5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients or history of severe hypersensitivity reactions to other monoclonal antibodies.
6. Patient has spinal cord compression or symptomatic brain metastases.
7. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Patients may receive treatment with bisphosphonates or receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors for the treatment of bone metastases.
8. History of active primary immunodeficiency.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1) Objective response rate (ORR)

Secondary endpoints 5

1. Overall Survival (OS).
2. Endpoints based on RECIST 1.1 including: Disease control rate (DCR)
3. Endpoints based on RECIST 1.1 including: Best percentage change in tumour size
4. Endpoints based on RECIST 1.1 including: Duration of response (DoR)
5. Endpoints based on RECIST 1.1 including: Progression free survival (PFS).

Investigational products

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

Test 3

Auxiliary 2

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

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

4 EU/EEA countries · 10 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 30 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