Study of efficacy and safety of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab in previously untreated locally advanced or metastatic non-squamous and squamous NSCLC subjects

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jan 2019 → 26 Jan 2026

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG, OMS ID: ORG-100003908

External identifiers

EU CT number

2024-511490-29-00

EudraCT number

2018-001547-32

ClinicalTrials.gov

NCT03631199

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Safety, Pharmacokinetic, Efficacy

Safety run-in part: To determine the recommended phase 3 dose regimen (RP3R) of canakinumab in combination with pembrolizumab plus platinum-based doublet chemotherapy.

Double-blind, randomized, placebo-controlled part: To compare progression free survival (PFS) by local investigator assessment as per RECIST 1.1 and overall survival (OS) between the two treatment arms.

Secondary objectives 9

1. Safety run-in part: 1. To characterize PK of canakinumab in combination with pembrolizumab plus platinum-based doublet chemotherapy
2. Safety Run-in part: 2. To characterize safety and tolerability of canakinumab in combination with pembrolizumab plus platinum-based doublet chemotherapy
3. Safety run-in part: 3. To assess preliminary clinical anti-tumor activity (ORR, DCR and DOR) of canakinumab in combination with pembrolizumab plus platinum-based chemotherapy
4. Safety run-in part: 4. To characterize immunogenicity (anti-drug antibodies) of canakinumab and pembrolizumab
5. Double-blind, randomized, placebo-controlled part: 1.To evaluate overall response rate (ORR), disease control rate (DCR), time to response (TTR) and duration of response (DOR) by local investigator assessment per RECIST 1.1 in the treatment arms.
6. Double-blind, randomized, placebo-controlled part: 2. To characterize the safety profile of the treatment arms.
7. Double-blind, randomized, placebo-controlled part: 3. To characterize pharmacokinetics of canakinumab, pembrolizumab and chemotherapy.
8. Double-blind, randomized, placebo-controlled part: 4. To characterize immunogenicity (anti-drug antibodies, ADA) of canakinumab and pembrolizumab
9. Double-blind, randomized, placebo-controlled part: 5. To assess PROs including symptoms, physical functioning and health-related quality of life in the treatment arms.

Conditions and MedDRA coding

Non-small cell lung cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Histologically confirmed locally advanced or metastatic NSCLC
2. 2. Measurable disease by RECIST 1.1
3. 3. Known PD-L1 status
4. 4. ECOG performance status (PS) ≤ 1.
5. 5. Other protocol-defined inclusion criteria may apply.

Exclusion criteria 8

1. 1. Previous immunotherapy or treatment with IL-1β inhibitor.
2. 2. Subjects with epidermal growth factor receptor (EGFR) sensitizing mutations and/or ALK rearrangement
3. 3. History of severe hypersensitivity reaction to monoclonal antibodies, platinum containing drugs, nab-paclitaxel, paclitaxel, pemetrexed or any known excipients of these drugs
4. 4. Other protocol-defined exclusion criteria may apply.
5. 5. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
6. 6. Presence or history of a malignant disease, other than NSCLC, that has been diagnosed and/or required therapy within the past 3 years prior to randomization.
7. 7. Active autoimmune disease that has required systemic treatment in the past 2 years prior to randomization (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Control of the disorder with replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is permitted.
8. 8. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Safety run-in part: Incidence of dose limiting toxicities in the first 42 days of study treatment.
2. Double-blind, randomized, placebo-controlled part: PFS based on local investigator assessment as per RECIST 1.1
3. Double-blind, randomized, placebo-controlled part: OS

Secondary endpoints 9

1. Safety run-in part: 1. Concentration and PK parameters of canakinumab, pembrolizumab and chemotherapy
2. Safety run-in part: 2. Type, frequency and severity of adverse events and reactions, changes in laboratory values, vital signs, ECGs
3. Safety run-in part: 3. ORR, DCR, DOR by investigator's assessment according to RECIST 1.1
4. Safety run-in part: 4. Anti-drug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment of canakinumab and pembrolizumab
5. Double-blind, randomized, placebo-controlled part: 1. ORR, DCR, TTR and DOR based on local investigator assessment as per RECIST 1.1
6. Double-blind, randomized, placebo-controlled part: 2. Frequency of adverse events, serious adverse events, AEs leading to treatment discontinuation, proportion of patients with laboratory abnormalities, ECG, and vital signs.
7. Double-blind, randomized, placebo-controlled part: 3. Concentration and PK parameters of canakinumab, pembrolizumab and chemotherapy
8. Double-blind, randomized, placebo-controlled part: 4. Anti-drug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment of canakinumab and pembrolizumab
9. Double-blind, randomized, placebo-controlled part: 5. Time to definitive 10-point deterioration symptom scores for chest pain, cough and dyspnea per QLQ-LC13 questionnaire as three primary PRO variables of interest and time to definitive deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30 as secondary PRO variables of interest.

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 13

Locations

2 EU/EEA countries · 3 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 26 files

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

Application history

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