A randomized, double-blind, placebo-controlled, phase III study evaluating the efficacy and safety of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab as first line therapy for locally advanced or metastatic non-squamous and squamous non-small cell lung cancer subjects (CANOPY-1)
PHRR190130-002039
CACZ885U2301
2018-CT0469
A randomized, double-blind, placebo-controlled, phase III study evaluating the efficacy and safety of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab as first line therapy for locally advanced or
metastatic non-squamous and squamous non-small cell lung cancer subjects (CANOPY-1)
Safety run-in part
This is an open label part to determine RP3R of canakinumab in combination with
pembrolizumab and platinum-based doublet chemotherapy.
Double-blind, randomized, placebo controlled part
This is a double-blind, randomized, placebo-controlled part to evaluate the efficacy and safety of canakinumab vs. canakinumab matching-placebo in combination with pembrolizumab plus platinum-based doublet chemotherapy followed by maintenance therapy.
| Start Date | Duration in Months | Target Completion Date | Actual Completion Date |
|---|---|---|---|
| 2019-08-22 | 42 | 2023-02-22 | 0000-00-00 |
Ongoing
| Institution | Classification | Region | LTO # |
|---|---|---|---|
| Novartis Healthcare Philippines, Inc. | Private Business | NCR | 3000006283930 |
| Institution | Region |
|---|---|
| Novartis Healthcare Philippines, Inc. | NCR |
| Name | Institution and Institution Address | |
|---|---|---|
| Anna Liza Calingasin | anna_liza.calingasin@novartis.com | Novartis Healthcare Philippines, Inc. 5/F Ayala North Exchange Tower 1 Salcedo corner Amorsolo Streets Legaspi Village, Makati City 1229 Philippines |
| Name | Institution and Institution Address | |
|---|---|---|
| Jerome Gonzaga | jerome.gonzaga@novartis.com | Novartis Healthcare Philippines, Inc. 5/F Ayala North Exchange Tower 1 Salcedo corner Amorsolo Streets Legaspi Village, Makati City 1229 Philippines |
| Name | Expertise | Affiliation |
|---|---|---|
| Christina G. Galvez, MD | Oncology | St Luke Medical Center - Global City |
| Joseph Parra, MD | Oncology | Makati Medical Center |
| Ma. Luisa Abesamis-Tiambeng, MD | Oncology | Cardinal Santos Medical Center |
| Priscilla B. Caguioa, MD | Oncology | St. Luke's Medcal Center Quezon City |
| Project Location | Institutional Ethics Review Board |
|---|---|
| St Luke Medical Center - Global City | N/A |
| Makati Medical Center | Makati Medical Center Institutional Review Board |
| Cardinal Santos Medical Center | Cardinal Santos Medical Center Ethics Review Committee |
| St. Luke's Medcal Center Quezon City | N/A |
locally advanced or metastatic non-squamous and squamous non-small cell lung cancer
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 progressive free survival (PFS) between the two treatment arms
To compare overall survival (OS) between the two treatment arms.
Safety run-in part:
To characterize the pharmacokinetics of canakinumab in combination with
pembrolizumab plus platinum-based doublet chemotherapy
To characterize the safety and tolerability of canakinumab in combination with
pembrolizumab plus platinum-based doublet chemotherapy
To characterize the immunogenicity (anti-drug antibodies) of canakinumab and
pembrolizumab
To assess the preliminary clinical anti-tumor activity (overall response rate, disease control rate and duration of response) of canakinumab in combination with pemrolizumab plus platinum-based doublet chemotherapy
Double-blind, randomized, placebo-controlled part:
To evaluate overall response rate (ORR), disease control rate (DCR), time to
response (TTR) and duration of response (DOR)
To characterize the safety profile of the two treatment arms.
To characterize the pharmacokinetics of canakinumab, pembrolizumab and
chemotherapy
To characterize the immunogenicity (anti-drug antibodies, ADA) of canakinumab and pembrolizumab.
To assess PROs in the two treatment arms
Completed
- Argentina
- Australia
- Austria
- Belgium
- Brazil
- Canada
- Chile
- China
- Colombia
- Czech Republic
- Denmark
- Finland
- France
- Germany
- Greece
- Guatemala
- Hong Kong
- Hungary
- Iceland
- India
- Italy
- Japan
- Lebanon
- Malaysia
- Mexico
- Netherlands
- New Zealand
- Norway
- Peru
- Philippines
- Poland
- Portugal
- Romania
- Russia
- Singapore
- Slovakia
- South Africa
- South Korea
- Spain
- Sweden
- Switzerland
- Taiwan
- Thailand
- Turkey
- United Kingdom
- United States
- Vietnam
Clinical Trial
20181012103520
2019-01-07
0000-00-00
8
8
Unspecified
2019-08-22
INCLUSION CRITERIA
1. Written informed consent must be obtained prior to any screening procedures
2. Adult male/female ≥ 18 years of age at the time of informed consent
3. Histologically confirmed locally advanced stage IIIB (and is not eligible for definitive
chemo-radiation curative therapy) or stage IV (metastatic) NSCLC for treatment in the
first-line setting
Subjects who received previous neo-adjuvant or adjuvant systemic therapy (other than
immunotherapies) will be eligible if neo-adjuvant or adjuvant therapy was completed at least 12 months prior to the development of metastatic disease. Last dose of neoadjuvant or adjuvant therapy must be more than 12 months prior to enrollment/randomization
4. Subject is a suitable candidate for platinum-doublet chemotherapy and pembrolizumab,
and does not have any contraindication(s) to these drugs as per locally approved label.
5. Known PD-L1 status determined by a Novartis designated central laboratory.
A newly obtained tissue biopsy or an archival biopsy (block or slides) is required for
PD-L1 determination (PD-L1 IHC 22C3 pharmDx assay), prior to study
randomization.
Note: For the safety run-in part, known PD-L1 status is not required.
6. ECOG performance status (PS) of 0 or 1.
7. At least 1 measurable lesion by RECIST 1.1 in solid tumors criteria; a previously irradiated lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation.
8. Subject must have recovered from all toxicities related to prior systemic therapy to grade
≤ 1 (CTCAE v5.0). Exception to this criterion: patients with any grade of alopecia
9. Subjects must have adequate bone marrow organ function including the following
laboratory values at the screening visit:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without growth factor support)
Platelets ≥ 100 x 109/L (without growth factor support or transfusion)
Hemoglobin (Hgb) > 9 g/dL (4 weeks without transfusions or erythropoietin)
Creatinine clearance greater than 60 mL/min by calculation using Cockcroft-Gault
formula
Total bilirubin (TBIL) ≤ 1.5 x ULN
Aspartate aminotransferase (AST) ≤ 3 x ULN
Alanine aminotransferase (ALT) ≤ 3 x ULN
Serum amylase ≤ 2 x ULN or pancreatic amylase ≤ 1.5 x ULN
Serum lipase ≤ ULN
10. Subject is able to communicate with the investigator, and has the ability to comply with
the requirements of the study procedures.
EXCLUSION CRITERIA
EXCLUSION CRITERIA
1. Previous immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody,
or any other antibody or drug specifically targeting T-cell co-stimulation or immune
checkpoint pathways).
2. Prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1β
inhibitor).
3. Subjects with epidermal growth factor receptor (EGFR) sensitizing mutations (identified
in exons 19, 20, or 21), and/or ALK rearrangement by locally approved laboratory testing
(If local testing is not available, a Novartis designated central laboratory will perform EGFR and/or ALK testing).
Subjects with NSCLC of pure squamous cell histology can initiate treatment without EGFR testing or result, however, subjects with pure squamous cell histology that are known to have EGFR sensitizing mutations are excluded.
4. History of severe hypersensitivity reaction to monoclonal antibodies, platinum containing
drugs, paclitaxel, nab-paclitaxel, pemetrexed or any known excipients of these drugs (i.e.
Polysorbate-80-containing infusions, mannitol, histidine).
7. Previously untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease.
Subjects with known CNS metastases that have been treated with radiotherapy and/or
surgery, without evidence of CNS disease progression ≥ 4 weeks after treatment
completion, and off corticosteroid therapy for ≥ 2 weeks prior to treatment start are
eligible
8. Presence or history of a malignant disease, other than NSCLC, that has been diagnosed
and/or required therapy within the past 3 years. Exceptions to this exclusion include the
following: completely resected basal cell and squamous cell skin cancers, and completely
resected carcinoma in situ of any type
9. Active, known, or suspected autoimmune disease or documented history of autoimmune
disease. Subjects with vitiligo, controlled type I diabetes mellitus on stable insulin, residual autoimmune-related hypothyroidism only requiring hormone replacement, or psoriasis not requiring systemic treatment are permitted.
10. Subject with suspected or proven immunocompromised state or infections, including:
Evidence of active or latent tuberculosis (TB) as determined by locally approved screening methods. If presence of TB (active or latent) is established then treatment for TB must have been completed according to locally approved country guidelines prior to screening for the study.
Chronic or active hepatitis B or C
Known history of testing positive for Human Immunodeficiency Virus (HIV)
infections. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
Any other medical condition (such as active infection, treated or untreated), which in the opinion of the investigator places the patient at an unacceptable risk for participation in immunomodulatory therapy.
Note: Subjects with localized condition unlikely to lead to a systemic infection
e.g. chronic nail fungal infection are eligible.
Allogeneic bone marrow or solid organ transplant
Treatment with any immune modulating
Interventional
pembrolizumab plus platinum-based doublet chemotherapy, canakinumab
Canakinumab (ACZ885) is a high-affinity human anti-interleukin-1β (IL-1β) monoclonal
antibody that belongs to the Immunoglobulin G1 (IgG1)/κ isotype subclass. Canakinumab is
manufactured in a murine SP2/0 cell line. Currently canakinumab is approved and marketed as Ilaris® for the treatment of IL
| Date | Amendment Classification | Reason |
|---|---|---|
| 2019-04-01 | Amendments related to the protocol | Informed consent |
| 2019-10-03 | Amendments related to the protocol | Informed consent |
| 2020-03-06 | Amendments related to the protocol | Informed consent |
| 2020-12-01 | Amendments related to the protocol | Informed consent |
Randomized
Double Blind
Only the investigational drug (canakinumab) will be blinded in this study. At the time of the final PFS analysis, both PFS and 1st IA for OS will be performed by an independent statistician and reviewed by a data monitoring committee (DMC). Unblinded results from the final PFS analysis and IA for OS will not be communicated to the Sponsor's clinical team or to any party involved in the study conduct (apart from the independent statistician and DMC members) until the DMC has determined that either:(i) final PFS or interim OS analyses has crossed the pre-specified boundary for efficacy or (ii) the study needs to be terminated due to any cause including safety reasons. If the final PFS and 1st IA for OS are not statistically significant, the 2nd IA for OS will also be done by an independent statistician. If the final PFS analysis is statistically significant, the sponsor’s clinical team will be unblinded and will perform the second OS interim and/or final OS analyses. Subjects, investigator, site personnel, persons performing the assessments, will remain blinded to the identity of the treatment from the time of randomization until OS results are statistically significant at one of the interim or final analyses.
Parallel
The purpose of this multicenter, randomized, double-blind, placebo-controlled phase III study
is to evaluate the efficacy and safety of canakinumab vs. canakinumab matching-placebo in
combination with pembrolizumab in addition to 4 cycles of platinum-based doublet induction
chemotherapy, followed by maintenance therapy in subjects with the overall response of stable
disease (SD) or better after completion of induction therapy, in subjects with locally advanced
stage or metastatic NSCLC. The double-blind, randomized, placebo-controlled part will be
preceded by a safety run-in part where the recommended dose of the combination of
canakinumab with pembrolizumab plus platinum-based doublet chemotherapy will be confirmed.
Phase III