A Phase II Study of MEDI4736 in Patients with Locally 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

23 Sep 2014 → 26 Mar 2025

Decision date (initial)

2024-05-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-512379-10-00

EudraCT number

2013-005427-16

ClinicalTrials.gov

NCT02087423

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Safety, Efficacy, Therapy, Pharmacokinetic

Cohort 1: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1 positive patients [abbr. PD-L1+pts] (≥25% of tumour cells with membrane staining [abbr. Tcwmst]).

Cohort 2: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1+pts (≥25% of Tcwmst).

Cohort 3: To assess the efficacy of MEDI4736 treatment in terms of ORR in PD-L1+pts with ≥90% of Tcwmst.

Secondary objectives 3

1. Assess efficacy of MEDI4736 Cohort 1: in terms of Duration of response (DoR), Disease control rate (DCR), Time to response (TTR), Progression free survival (PFS), and Overall survival (OS) in PD-L1+pts (≥25% of Tcwmst). Cohort 2, key sec objectives: in terms of ORR in Non-squamous [NSq] PD-L1+pts, PD-L1+pts with ≥90% of Tcwmst, NSq PD-L1+pts with ≥ 90% of Tcwmst.
2. Other sec objectives: In terms of DoR, DCR, TTR, PFS and OS in PDL1+ pts, NSq PD-L1+pts, PD-L1+pts with ≥90% of Tcwmst, NSq PDL1+ pts with ≥90% of Tcwmst. Assess efficacy of MEDI4736 in PD-L1-pts (<25% of Tcwmst), NSq PD-L1-pts, PD-L1 unselected pts, PD-L1+pts with <90% of TCwmst, NSq PD-L1+pts with <90% of TCwmst. Cohorts 2 and 3: in a combined population of Cohorts 2 and 3 for: PD-L1+ pts / NSq PD-L1+pts with ≥90% of Tcwmst. Cohort 3: in terms of DoR, DCR, TTR, PFS and OS in PD-L1+pts with ≥ 90% of Tcwmst.
3. All cohorts: Assess safety, tolerability, PK and immunogenicity profile of MEDI4736

Conditions and MedDRA coding

Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIBIV)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Provision of signed, written and dated informed consent prior to any study specific procedures
2. Male or female aged 18 years or older
3. Patients must have EITHER • Histologically- or cytologically-documented NSCLC, OR • Recurrent or progressive disease following multimodal therapy for locally advanced disease
4. Patients must have received at least 2 prior systemic treatment regimens for treatment of NSCLC
5. Patients must have experienced disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional systemic therapy
6. Patient's tumour sample must be PD-L1 positive with ≥25% of tumour cells with membrane staining (Cohorts 1 and 2) or PD-L1 positive with ≥ 90% of tumour cells with membrane staining (Cohort 3).
7. Patients must have measurable disease
8. Life expectancy ≥12 weeks at Day 1
9. World Health Organisation (WHO) Performance Status of 0 or 1
10. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients
11. Adequate organ and marrow function

Exclusion criteria 22

1. Participation in another clinical study with an investigational product (IMP) during the last 4 weeks
2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
3. Mixed small cell and NSCLC histology
4. Receipt of any immunotherapy, or IMP within 4 weeks prior to the first dose of study drug
5. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
6. Any unresolved toxicity CTCAE >Grade 2 from previous anti-cancer therapy
7. Any prior Grade ≥3 immune-related adverse event (irAE) while Receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
8. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
9. Receipt of radiation therapy within 4 weeks prior to starting MEDI4736, or limited field of radiation for palliation within 2 weeks of the first dose of MEDI4736
10. Recent major surgery within 4 weeks
11. Active or prior documented autoimmune disease within the past 2 years, except for: Vitiligo, Grave's disease, or psoriasis not requiring systemic treatment
12. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
13. History of primary immunodeficiency
14. History of allogeneic organ transplant
15. History of hypersensitivity to MEDI4736 or any excipient
16. Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 1 month prior to entry into the study
17. Uncontrolled intercurrent illness
18. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736
19. History of another primary malignancy except for: • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease • Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ.
20. Female patients who are pregnant or breast-feeding. Male or female patients of reproductive potential who are not using an effective method of birth control
21. Any condition that, in the opinion of the investigator, would interfere with evaluation of MEDI4736 or interpretation of patient safety or study results
22. Absence of a tumour sample (archival and recent).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR) (per RECIST 1.1) Timepoint(s) of evaluation of this end point For each cohort, the data cut-off for the analysis of ORR will take place approximately 24 weeks after the last patient is enrolled into each cohort.

Secondary endpoints 1

1. - Duration of response - Progression free survival - Disease control rate - Overall survival - Deep sustained response - AEs Timepoint(s) of evaluation of this end point The data cut-off for analysis of the secondary efficacy endpoints will take place approximately 8 months after recruitment ends. The final analysis of OS (secondary endpoint) will take place approximately 12 months after the last patient is enrolled into each cohort.

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

1 EU/EEA country · 1 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 29 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