Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy

NCT ID: NCT03626545

Last Updated: 2023-08-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 245 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-23
• Study Completion Date: 2021-12-20

Brief Summary

This study was designed to evaluate the role of canakinumab in combination with docetaxel in subjects with advanced non-small cell lung cancer (NSCLC) previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy.

Detailed Description

This was a multicenter, Phase III study designed to evaluate the efficacy and safety of canakinumab in combination with docetaxel versus placebo in combination with docetaxel, as second- or third-line treatment. The study included adult subjects with advanced NSCLC whose disease had progressed after prior treatment with a PD-(L)1 inhibitor. Subjects had also been pre-treated with platinum-based chemotherapy, either given together with PD-(L)1 inhibitor or sequentially.

The study consisted of 2 parts:

• Part 1: Safety run-in. This part was conducted to confirm the Recommended Phase 3 Regimen (RP3R) of the canakinumab and docetaxel combination. Participants were treated for at least 2 complete cycles of treatment (21 days per cycle) for safety evaluation (DLT-Dose Limiting Toxicities) to define RP3R. Participants from the safety run-in part were treated until any discontinuation criteria were met. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow up period (up to 130 days). Additionally, subjects who discontinued study treatment without prior documented disease progression continued efficacy assessments in the efficacy follow-up phase irrespective of the start of new antineoplastic therapy and until documented progressive disease as per protocol. After the RP3R was determined, enrollment in this part was closed and additional participants were enrolled in the randomized part (part 2) of the study. Ongoing patients from the safety run-in part continued their treatment at the assigned dose level according to the dose and schedule for the safety run-in part.
• Part 2: Randomized part. The randomized, double-blind, placebo-controlled part of the study opened after confirmation of the RP3R for the combination of canakinumab and docetaxel. Participants from the randomized part were treated until any discontinuation criteria were met as per protocol. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow up period (up to 130 days). Additionally, subjects who discontinued study treatment without prior documented disease progression continued efficacy assessments in the efficacy follow-up phase irrespective of the start of new antineoplastic therapy and until documented progressive disease as per protocol.

Based on the lack of efficacy observed in the primary analysis, Novartis decided to halt canakinumab/placebo treatment. Subjects continued to receive docetaxel if they were deriving clinical benefit as per investigator assessment until discontinuation

Conditions

Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Safety run-in part: Canakinumab+docetaxel

Participants were treated with full doses of docetaxel 75mg/m\^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1). Subjects were assessed for at least 2 complete cycles of treatment (21 days per cycle; a total of 42 days) for safety evaluation (DLT) to define RP3R. De-escalation to canakinumab 200 mg subcutaneous every 6 weeks + docetaxel 75 mg/m\^2, every 3 weeks could also be considered.

Group Type: EXPERIMENTAL

Canakinumab

Intervention Type: DRUG

Canakinumab, 200 mg, subcutaneous. The initial dose regimen was once every 3 weeks (on Day 1 of each 21-day cycle)

Docetaxel

Intervention Type: DRUG

Docetaxel 75mg/m\^2, intravenous, administered on Day 1 of each 21-day cycle

Randomized part: Canakinumab + docetaxel

Participants were treated with canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m\^2 every 3 weeks

Group Type: EXPERIMENTAL

Canakinumab

Intervention Type: DRUG

Canakinumab, 200 mg, subcutaneous. The initial dose regimen was once every 3 weeks (on Day 1 of each 21-day cycle)

Docetaxel

Intervention Type: DRUG

Docetaxel 75mg/m\^2, intravenous, administered on Day 1 of each 21-day cycle

Randomized part: Placebo + docetaxel

Participants were treated with placebo subcutaneous at RP3R and docetaxel at 75 mg/m\^2 every 3 weeks

Group Type: PLACEBO_COMPARATOR

Docetaxel

Intervention Type: DRUG

Docetaxel 75mg/m\^2, intravenous, administered on Day 1 of each 21-day cycle

Placebo

Intervention Type: OTHER

Placebo, sub-cutaneous, admnistered at the RP3R defined in Part 1-safety run-in.

Interventions

Canakinumab

Canakinumab, 200 mg, subcutaneous. The initial dose regimen was once every 3 weeks (on Day 1 of each 21-day cycle)

Intervention Type: DRUG

Docetaxel

Docetaxel 75mg/m\^2, intravenous, administered on Day 1 of each 21-day cycle

Intervention Type: DRUG

Placebo

Placebo, sub-cutaneous, admnistered at the RP3R defined in Part 1-safety run-in.

Intervention Type: OTHER

Other Intervention Names

ACZ885

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed advanced (stage IIIB) or metastatic NSCLC.
• Subject had received one prior platinum-based chemotherapy and one prior PD-(L)1 inhibitor therapy for locally advanced or metastatic disease.
• Subject with ECOG performance status (PS) of 0 or 1.
• Subject with at least 1 evaluable (measurable or non-measurable) lesion by RECIST 1.1 in solid tumors criteria.

Exclusion Criteria

• Subject who previously received docetaxel, canakinumab (or another IL-1β inhibitor), or any systemic therapy for their locally advanced or metastatic NSCLC other than one platinum-based chemotherapy and one prior PD-(L)1 inhibitor.
• Subject with EGFRor ALK positive tumor.
• History of severe hypersensitivity reaction to monoclonal antibodies, taxanes or excipients of docetaxel or canakinumab.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Emory Winship Cancer Institute

Atlanta, Georgia, United States

Saint Luke's Hospital/Marion Bloch Neuroscience Institute Dept of Regulatory

Kansas City, Missouri, United States

Montefiore Medical Center Albert Einstein College of Med

The Bronx, New York, United States

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

MD Anderson

Houston, Texas, United States

Huntsman Cancer Institute Univ of Utah .

Salt Lake City, Utah, United States

Novartis Investigative Site

Berazategui, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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La Rioja, , Argentina

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Santiago del Estero, , Argentina

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Greenslopes, Queensland, Australia

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Shepparton, Victoria, Australia

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Sint-Niklaas, Oost Vlaanderen, Belgium

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Brussels, , Belgium

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Charleroi, , Belgium

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Ghent, , Belgium

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Roeselare, , Belgium

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Salvador, Estado de Bahia, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Itajaí, Santa Catarina, Brazil

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Vancouver, British Columbia, Canada

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Montreal, Quebec, Canada

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Santiago, , Chile

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Chengdu, Sichuan, China

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Shanghai, , China

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Brno - Bohunice, , Czechia

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Ostrava Vitkovice, , Czechia

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Herlev, , Denmark

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Odense C, , Denmark

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Le Mans, Cedex 09, France

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Besançon, , France

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Bordeaux, , France

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Bron, , France

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Strasbourg, , France

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Berlin, , Germany

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Cologne, , Germany

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Dresden, , Germany

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Frankfurt, , Germany

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Gerlingen, , Germany

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Großhansdorf, , Germany

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Ulm, , Germany

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Heraklion Crete, Greece, Greece

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Thessaloniki, , Greece

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Törökbálint, Pest County, Hungary

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Ramat Gan, , Israel

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Lucca, LU, Italy

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Rozzano, MI, Italy

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Aviano, PN, Italy

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Nagoya, Aichi-ken, Japan

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Himeji, Hyōgo, Japan

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Yokohama, Kanagawa, Japan

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Chuo Ku, Tokyo, Japan

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Osaka, , Japan

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Amman, , Jordan

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El Achrafiyé, , Lebanon

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Maastricht, , Netherlands

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Gdansk, , Poland

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Rzeszów, , Poland

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Warsaw, , Poland

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Pushkin Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Singapore, , Singapore

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Seoul, Seocho Gu, South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Málaga, Andalusia, Spain

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Badalona, Catalonia, Spain

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A Coruña, Galicia, Spain

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Valencia, Valencia, Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Tainan City, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; Chile; China; Czechia; Denmark; France; Germany; Greece; Hungary; Israel; Italy; Japan; Jordan; Lebanon; Netherlands; Poland; Russia; Singapore; South Korea; Spain; Taiwan

References

Paz-Ares L, Goto Y, Wan-Teck Lim D, Halmos B, Chul Cho B, Cobo M, Luis Gonzalez Larriba J, Zhou C, Demedts I, Atmaca A, Baka S, Mookerjee B, Portella S, Zhu Z, Wu J, Demanse D, Dharan B, Reck M. Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced non-small cell lung cancer following platinum-based doublet chemotherapy and immunotherapy (CANOPY-2): A multicenter, randomized, double-blind, phase 3 trial. Lung Cancer. 2024 Mar;189:107451. doi: 10.1016/j.lungcan.2023.107451. Epub 2024 Jan 16.

Reference Type: DERIVED

PMID: 38354535 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1221

A Plain Language Trial Summary is available on novctrd.com

Other Identifiers

2018-002480-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CACZ885V2301

Identifier Type: -

Identifier Source: org_study_id