E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
stages AJCC v. 8 IIIB/IIIC (not eligible for definite chemoradiation
therapy) or stage IV (metastatic) non-small cell lung cancer (NSCLC) |
|
E.1.1.1 | Medical condition in easily understood language |
locally advanced or metastatic non-small cell lung cancer (NSCLC) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
Safety run-in part:
1. To characterize PK of canakinumab in combination with pembrolizumab plus platinum-based doublet chemotherapy
2. To characterize safety and tolerability of canakinumab in combination with pembrolizumab plus platinum-based doublet chemotherapy
3. To assess preliminary clinical anti-tumor activity (ORR, DCR and DOR) of canakinumab in combination with pembrolizumab plus platinum-based chemotherapy
4. To characterize immunogenicity (anti-drug antibodies) of canakinumab and pembrolizumab
Double-blind, randomized, placebo-controlled part:
1. To evaluate ORR, DCR, time to response and DOR by local investigator assessment per RECIST 1.1 in the treatment arms
2. To characterize the safety profile of the treatment arms
3. To characterize PK of canakinumab, pembrolizumab and chemotherapy
4. To characterize immunogenicity (ADA) of canakinumab and pembrolizumab
5. To assess PROs including symptoms, physical functioning and health-related QOL in the treatment arms |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed locally advanced or metastatic NSCLC
2. Measurable disease by RECIST 1.1
3. Known PD-L1 status
4. ECOG performance status (PS) ≤ 1.
5. Other protocol-defined inclusion criteria may apply. |
|
E.4 | Principal exclusion criteria |
1. Previous immunotherapy or treatment with IL-1β inhibitor.
2. Subjects with epidermal growth factor receptor (EGFR) sensitizing
mutations and/or ALK rearrangement
3. History of severe hypersensitivity reaction to monoclonal antibodies,
platinum containing drugs, nab-paclitaxel, paclitaxel, pemetrexed or any
known excipients of these drugs
4. Other protocol-defined exclusion criteria may apply.
5. Known active central nervous system (CNS) metastases and/or
carcinomatous meningitis.
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. 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.
13. History of (non-infectious) pneumonitis that required steroids or
current pneumonitis. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety run-in part: Incidence of dose limiting toxicities in the first 42 days of study treatment.
Double-blind, randomized, placebo-controlled part: PFS based on local investigator assessment as per RECIST 1.1 and OS |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety run-in part:
The analysis will be conducted when at least 6 evaluable subjects (among approximately 9 subjects enrolled) in each of the 3 treatment cohorts have been observed for dose limiting toxicity (DLT) for at least 42 days.
Double-blind, randomized, placebo-controlled part:
In the primary analysis, PFS analysis and OS analysis will occur when approximately 253 PFS events are observed. |
|
E.5.2 | Secondary end point(s) |
Safety run-in part:
1. Concentration and PK parameters of canakinumab, pembrolizumab and chemotherapy
2. Type, frequency and severity of adverse events and reactions, changes in laboratory values, vital signs, ECGs
3. ORR, DCR, DOR by investigator’s assessment according to RECIST 1.1
4. Anti-drug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment of canakinumab and pembrolizumab
Double-blind, randomized, placebo-controlled part:
1. ORR, DCR, TTR and DOR based on local investigator assessment as per RECIST 1.1
2. Frequency of adverse events, serious adverse events, AEs leading to treatment discontinuation, proportion of patients with laboratory abnormalities, ECG, and vital signs.
3. Concentration and PK parameters of canakinumab, pembrolizumab and chemotherapy
4. Anti-drug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment of canakinumab and pembrolizumab
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. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety run-in part:
The analysis will be conducted when at least 6 evaluable subjects (among approximately 9 subjects enrolled) in each of the 3 treatment cohorts have been observed for dose limiting toxicity (DLT) for at least 42 days.
Double-blind, randomized, placebo-controlled part:
Analysis will occur when approximately 253 PFS events are observed. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient reported outcomes |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 101 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
Chile |
China |
Colombia |
Guatemala |
Hong Kong |
India |
Japan |
Korea, Republic of |
Lebanon |
Malaysia |
Mexico |
Peru |
Philippines |
Russian Federation |
Singapore |
South Africa |
Taiwan |
Thailand |
Turkey |
United States |
Vietnam |
Austria |
Denmark |
Finland |
France |
Germany |
Hungary |
Iceland |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
Argentina |
Greece |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study will end when five years have passed from the time of the
last subject first treatment in the randomized part or when all subjects
discontinue the study treatment and complete their safety follow up,
die, withdraw consent or are lost to follow up, whichever comes first. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 4 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 25 |