Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation 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

11 Feb 2019 → ongoing

Decision date (initial)

2024-06-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-509602-29-00

EudraCT number

2018-000867-10

ClinicalTrials.gov

NCT03703297

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS
To assess the efficacy of durvalumab monotherapy compared to placebo in terms of OS

Secondary objectives 1

1. To assess : - the efficacy of durvalumab and tremelimumab combination (D+T) vs placebo in terms of PFS and OS - the efficacy of durvalumab monotherapy (D) and D+T combination vs placebo in terms of ORR, PFS18, PFS24, TTDM, OS24, OS36 and PFS2 - the efficacy of D+T combination vs D in terms of PFS, ORR and OS - disease-related symptoms and HRQoL in patients treated with D and D+T combination vs placebo using the EORTC QLQ-C30 v3 and QLQ-LC13 - PK of D and D+T combination - safety and tolerability of D and D+T combination vs placebo To investigate: - the immunogenicity of D and D+T combination - the relationship between PD L1 expression and spatial distribution for D or D+T combination therapy

Conditions and MedDRA coding

Patients with Limited Stage Small-Cell Lung Cancer (LS-SCLC)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

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 1

1. Histologically or cytologically documented limited-stage SCLC (Stage I-III SCLC any, N any, i.e., patients whose disease can be encompassed within a radical radiation portal - Patients with Stage I to IIA disease must be medically inoperable as determined by investigator. Received an appropriate first line concurrent chemoradiotherapy regimen as defined below, unless after consultation with the global study medical team an alternative is acceptable, received 4 cycles of platinum-based chemotherapy concurrent with RT, which must be completed within 1 to 42 days prior to first dose of IP. The chemotherapy regimen must contain platinum and IV etoposide administered, as per local standard-of-care regimens. The radiotherapy must have commenced no later than the end of Cycle 2 of chemotherapy and patients must have received a total dose of radiation of 60 to 66 Gy over 6 weeks for standard QD radiation schedules or 45 Gy over 3 weeks for hyperfractionated BID radiation schedules. Patients must have achieved CR, PR, or SD and not have progressed following definitive, platinum-based chemotherapy, concurrent with RT. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment and randomization. Mandatory availability of tumor sample, which may include a core needle biopsy, newly cut unstained slides, or fine needle aspirate (FNA) cell block samples. Tissue sample should be submitted before or within 60 days of randomization. However, patients may be enrolled into the study before the pre-treatment tumor tissue sample is submitted. A newly acquired tumor biopsy (taken following completion of chemoradiotherapy) is optional, provided that a biopsy procedure is technically feasible, and the procedure is not associated with unacceptable clinical risk. PCI may be delivered at the discretion of investigator and per local standard of care, and completion within 42 days of completion of concurrent CRT.

Exclusion criteria 1

1. Extensive-stage SCLC. Mixed SCLC and NSCLC histology. Brain metastases or spinal cord compression. All patients will have an MRI (preferred) or CT, preferably with IV contrast of the brain, after completion of first line concurrent chemoradiotherapy and within 1 to 42 days prior to randomization and the first dose of IP. Patients who received sequential chemoradiation therapy for LS-SCLC (no overlap of RT with chemotherapy). Receipt of chemotherapy that exceeds 4 cycles in total. Chemotherapy regimens other than etoposide and platinum are not permitted. Any history of Grade ≥2 pneumonitis Active or prior documented autoimmune/inflammatory disorders, uncontrolled intercurrent illness or active infections Prior exposure to immune-mediated therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS using BICR assessments according to RECIST 1.1 OS

Secondary endpoints 2

1. PFS, ORR, PFS18, PFS24, and TTDM using BICR assessments according to RECIST 1.1 OS, OS24, OS36 PFS2 EORTC QLQ-C30 and QLQ-LC13: change in symptoms, functioning, and global health status/QoL Concentration of durvalumab and tremelimumab in serum (such as peak concentration and trough; sparse sampling) Presence of ADA for durvalumab and tremelimumab
2. PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS, and ORR). Safety assessment: AEs; laboratory findings including clinical chemistry, hematology, urinalysis; physical examinations; vital signs including blood pressure and pulse; and electrocardiograms

Investigational products

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

Test 2

Placebo 2

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

Locations

7 EU/EEA countries · 44 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 58 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