A clinical trial to evaluate if CC-486 plus pembrolizumab works and is safe in patients with advanced or metastatic non-small cell lung cancer who have previously received platinum containing treatment.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Dec 2015 → 8 Jul 2025

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Celgene Corporation

External identifiers

EU CT number

2024-513405-31-00

EudraCT number

2014-005614-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To estimate the efficacy of CC-486 plus pembrolizumab versus pembrolizumab plus placebo based on PFS as measured using RECIST 1.1 criteria

Secondary objectives 5

1. To estimate DCR of CC-486 plus pembrolizumab versus pembrolizumab plus placebo
2. To estimate OS of CC-486 plus pembrolizumab versus pembrolizumab plus placebo
3. To estimate ORR of CC-486 plus pembrolizumab versus pembrolizumab plus placebo
4. To evaluate safety and tolerability of CC-486 plus pembrolizumab versus pembrolizumab plus placebo
5. To evaluate the impact of pembrolizumab on the pharmacokinetics of CC-486

Conditions and MedDRA coding

Second-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Subject is ≥ 18 years of age at the time of signing the informed consent form.
2. Subject has histologically or cytologically confirmed squamous or nonsquamous NSCLC.
3. Subject has stage IIIB or IV NSCLC and was pretreated with only 1 prior systemic platinum based chemotherapy.
4. Subject has provided a formalin fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated to assess for PD-L1 status.
5. Subject has radiographically-documented measurable disease, as per RECIST 1.1.
6. Subject has an ECOG performance status of 0 to 1.
7. Subject has adequate organ and bone marrow functions

Exclusion criteria 7

1. Subject with non-squamous histology has known or unknown sensitizing EGFR and/or positive ALK mutation Note: Subjects with squamous histology and unknown EGFR and ALK mutational status are eligible.
2. Subject has received more than one line of therapy for stage IIIB or IV disease.
3. Subject has received prior therapy with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanism
4. Subject has had radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting IP, and/or from whom ≥ 30% of the bone marrow was irradiated.
5. Subject has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
6. Subject has active autoimmune disease that has required systemic treatment within the past 2 years
7. Subject with uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. *Subjects with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases (must include radiotherapy and/or surgery) >= 28 days (>= 14 days for stereotactic radiosurgery). Patients must not be receiving corticosteroids for brain metastases.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS measured as time from randomization to progression according to RECIST 1.1 (based on Investigator assessment)

Secondary endpoints 5

1. Number (%) of subj. with SD for ≥ 18 weeks, complete response (CR) or PR (DCR).
2. Overall survival.
3. Number (%) of subj. who achieve an objective CR or PR (ORR).
4. Safety to include the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, Grade 3-4 TEAEs, TEAEs of special interest, and laboratory abnormalities and other safety parameters.
5. Plasma PK parameters such as maximum observed concentration (Cmax), area under the concentration-time curve (AUC), time to maximum concentration (Tmax), terminal half-life (t1/2), apparent total body clearance (CL/F) and apparent volume of distribution (Vz/F) for CC-486.

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 4

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

Documents 7 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