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

NCT03626545 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CACZ885V23012018-002480-26
• Study Type: interventional
• Target: 245
• Locations: 26 countries
• Sites: 78

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.

Conditions

Non-Small-Cell Lung

Keywords

ACZ885; canakinumab; docetaxel; NSCLC; Non Small Cell Lung Cancer; Carcinoma; IL-1β; PD-(L)1; CANOPY; CANOPY-2; second or third line therapy; PD-(L)1 inhibitors; platinum-based chemotherapy

Outcome Measures

Primary Outcomes (2)

• Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)

  Percentage of participants with DLTs. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 42 days of docetaxel and canakinumab treatment.

  During the first 42 days of dosing

• Randomized Part: Overall Survival (OS)

  OS is defined as the time from randomization to date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a subject was not known to have died, then OS was censored at the latest date the subject was known to be alive (on or before the cut-off date).

  From randomization until death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approximately (approx.) 18 months)

Secondary Outcomes (22)

• Overall Response Rate (ORR)

  Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)

• Duration of Response (DOR)

  From first documented response of CR or PR to date of first documented progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 10 months for the safety run-in and 18 months for the randomized)

• Disease Control Rate (DCR)

  Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)

• Randomized Part: Progression-Free Survival (PFS)

  From randomization until disease progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (assessed up to approx. 18 months)

• Randomized Part: Time to Response (TTR)

  From randomization until first documented response or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 18 months)

Study Arms (3)

Safety run-in part: Canakinumab+docetaxel

EXPERIMENTAL

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.

Drug: Canakinumab; Drug: Docetaxel

Randomized part: Canakinumab + docetaxel

EXPERIMENTAL

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

Drug: Canakinumab; Drug: Docetaxel

Randomized part: Placebo + docetaxel

PLACEBO COMPARATOR

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

Drug: Docetaxel; Other: Placebo

Interventions

Canakinumab DRUG

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

Also known as: ACZ885

Randomized part: Canakinumab + docetaxel; Safety run-in part: Canakinumab+docetaxel

Docetaxel DRUG

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

Randomized part: Canakinumab + docetaxel; Randomized part: Placebo + docetaxel; Safety run-in part: Canakinumab+docetaxel

Placebo OTHER

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

Randomized part: Placebo + docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (78)

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

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

Kansas City, Missouri, 64111, United States

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Montefiore Medical Center Albert Einstein College of Med

The Bronx, New York, 10461, United States

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University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

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MD Anderson

Houston, Texas, 77030, United States

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Huntsman Cancer Institute Univ of Utah .

Salt Lake City, Utah, 84112 0550, United States

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Novartis Investigative Site

Berazategui, Buenos Aires, B1884BBF, Argentina

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Novartis Investigative Site

CABA, Buenos Aires, C1426ANZ, Argentina

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Mar del Plata, Buenos Aires, B7600FZN, Argentina

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La Rioja, 5300, Argentina

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Santiago del Estero, 4200, Argentina

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Greenslopes, Queensland, 4120, Australia

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Shepparton, Victoria, 3630, Australia

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Sint-Niklaas, Oost Vlaanderen, 9100, Belgium

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Brussels, 1200, Belgium

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Charleroi, 6000, Belgium

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Ghent, 9000, Belgium

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Roeselare, 8800, Belgium

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Salvador, Estado de Bahia, 40170-110, Brazil

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Porto Alegre, Rio Grande do Sul, 90880-480, Brazil

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Itajaí, Santa Catarina, 88301-229, Brazil

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Vancouver, British Columbia, V5Z 4E6, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Santiago, 7500006, Chile

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Chengdu, Sichuan, 610041, China

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Shanghai, 200433, China

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Brno-Bohunice, 625 00, Czechia

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Ostrava Vitkovice, 703 84, Czechia

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Herlev, DK 2730, Denmark

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Odense C, DK 5000, Denmark

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Le Mans, Cedex 09, 72037, France

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Besançon, 25030, France

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Bordeaux, 33000, France

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Bron, 69677, France

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Strasbourg, 67091, France

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Berlin, 13125, Germany

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Cologne, 51109, Germany

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Dresden, 01307, Germany

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Frankfurt, 60488, Germany

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Gerlingen, 70839, Germany

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Großhansdorf, 22947, Germany

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Ulm, 89081, Germany

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Heraklion Crete, Greece, 711 10, Greece

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Thessaloniki, 57001, Greece

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Törökbálint, Pest County, 2045, Hungary

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Ramat Gan, 52621, Israel

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Lucca, LU, 55100, Italy

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Rozzano, MI, 20089, Italy

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Aviano, PN, 33081, Italy

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Nagoya, Aichi-ken, 464 8681, Japan

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Himeji, Hyōgo, 670-8520, Japan

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Yokohama, Kanagawa, 241-8515, Japan

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Chuo Ku, Tokyo, 104 0045, Japan

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Osaka, 545-8586, Japan

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Amman, 11941, Jordan

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El Achrafiyé, 166830, Lebanon

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Amsterdam, 1081 HV, Netherlands

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Groningen, 9713 GZ, Netherlands

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Maastricht, 6229 HX, Netherlands

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Gdansk, 80 952, Poland

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Rzeszów, 35-021, Poland

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Warsaw, 02 781, Poland

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Pushkin Saint Petersburg, 196603, Russia

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Saint Petersburg, 197758, Russia

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Singapore, 168583, Singapore

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Seoul, Seocho Gu, 06591, South Korea

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Seoul, 03722, South Korea

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Novartis Investigative Site

Seoul, 05505, South Korea

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Málaga, Andalusia, 29010, Spain

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Badalona, Catalonia, 08916, Spain

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A Coruña, Galicia, 15006, Spain

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Valencia, Valencia, 46014, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, 28040, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Madrid, 28222, Spain

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Tainan, 70403, Taiwan

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Novartis Investigative Site

Taipei, 103616, Taiwan

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Related Publications (1)

• 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.

  PMID: 38354535 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma; Neoplasm Metastasis

Interventions

canakinumab; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Study director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2018
• First Posted: August 13, 2018
• Study Start: January 23, 2019
• Primary Completion: January 8, 2021
• Study Completion: December 20, 2021
• Last Updated: August 21, 2023
• Results First Posted: June 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

LE (1); TW (2); AR (5); RU (2); AU (2); CL (1); DK (2); US (6); CA (2); JO (1); HU (1); ES (8); GR (2); CZ (2); BE (5); IL (1); FR (5); IT (3); DE (7); BR (3); PL (3); KR (3); JP (5); NL (3); SG (1); CN (2)