Study of Oral cMET Inhibitor INC280 in Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC) (Geometry Mono-1)

NCT02414139 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CINC280A22012014-003850-15
• Study Type: interventional
• Target: 373
• Locations: 20 countries
• Sites: 95

Brief Summary

Study to evaluate the efficacy and safety of capmatinib as a single-agent treatment for subjects with advanced/metastatic (stage IIIB or IV) non-small cell lung cancer (NSCLC) who had wild-type epidermal growth factor receptor (EGFR wt) (for exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK)-negative rearrangement, and mesenchymal epithelial transition (MET) mutations leading to exon 14 deletion (referred to as MET mutation hereafter) and/or MET amplification.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non Small Cell Lung; Non Small Cell Lung Cancer; Non-small cell lung cancer; NSCLC; INC280; EGFR wild-type (wt); advanced non-small cell lung cancer; advanced/metastatic disease; Non-small cell lung carcinoma (NSCLC); treatment of lung cancer after first metastasis; lung cancer; lung adenocarcinoma; Non small cell lung carcinoma; MET exon 14 deletion; METex14del; MET exon 14 skipping; MET exon 14 mutation; MET mutation; MET amplification; MET inhibitor; MET dysregulation; MET activation; MET signaling; MET pathway; met; cMET; Geometry mono-1; Geometry

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment

  Percentage of participants with a best overall response defined as confirmed complete response (CR) or partial response (PR) by BIRC assessment per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  Up to approximately 5 years

Secondary Outcomes (17)

• Duration of Response (DOR) by BIRC Assessment

  Up to approximately 5 years

• ORR by Investigator Assessment

  Up to approximately 5 years

• DOR by Investigator Assessment

  Up to approximately 5 years

• Time to Response (TTR) by BIRC Assessment

  Up to approximately 5 years

• TTR by Investigator Assessment

  Up to approximately 5 years

Study Arms (10)

Cohort 1a: Pre-treated patients with MET GCN ≥ 10 (2/3L)

EXPERIMENTAL

Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)

Drug: Capmatinib

Cohort 1b:Pre-treated patients with MET GCN ≥ 6 and < 10 (2/3L)

EXPERIMENTAL

Pre-treated patients with MET GCN ≥ 6 and \< 10 treated with INC280 at 400 mg BID as second or third line (2/3L)

Drug: Capmatinib

Cohort 2: Pre-treated patients with MET GCN ≥ 4 and < 6 (2/3L)

EXPERIMENTAL

Pre-treated patients with MET GCN ≥ 4 and \< 6 treated with INC280 at 400mg BID as second or third line (2/3L)

Drug: Capmatinib

Cohort 3: Pre-treated patients with MET GCN < 4 (2/3L)

EXPERIMENTAL

Pre-treated patients with MET GCN \< 4 treated with INC280 at 400mg BID as second or third line (2/3L)

Drug: Capmatinib

Cohort 4: Pre-treated patients with MET mutation regardless of MET GCN (2/3L)

EXPERIMENTAL

Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)

Drug: Capmatinib

Cohort 5a: Treatment-naïve patients with MET GCN ≥10 (1L)

EXPERIMENTAL

Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)

Drug: Capmatinib

Cohort 5b: Treatment-naïve patients with MET mutation regardless of MET GCN (1L)

EXPERIMENTAL

Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)

Drug: Capmatinib

Cohort 6.1 (expansion of Cohort 1a): Pre-treated patients MET GCN ≥ 10 without MET mutation (2L)

EXPERIMENTAL

Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)

Drug: Capmatinib

Cohort 6.2 (expansion of Cohort 4): Pre-treated patients with MET mutation (2L)

EXPERIMENTAL

Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)

Drug: Capmatinib

Cohort 7 (expansion of Cohort 5b): Treatment-naïve with MET mutation regardless of MET GCN (1L)

EXPERIMENTAL

Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)

Drug: Capmatinib

Interventions

Capmatinib DRUG

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. Capmatinib was administered to participants in Cohorts 1a, 1b, 2, 3, 4, 5a and 5b in a fasted state. For Cohorts 6.1. 6.2 and 7, capmatinib was administered either with or without food.

Also known as: INC280

Cohort 1a: Pre-treated patients with MET GCN ≥ 10 (2/3L); Cohort 1b:Pre-treated patients with MET GCN ≥ 6 and < 10 (2/3L); Cohort 2: Pre-treated patients with MET GCN ≥ 4 and < 6 (2/3L); Cohort 3: Pre-treated patients with MET GCN < 4 (2/3L); Cohort 4: Pre-treated patients with MET mutation regardless of MET GCN (2/3L); Cohort 5a: Treatment-naïve patients with MET GCN ≥10 (1L); Cohort 5b: Treatment-naïve patients with MET mutation regardless of MET GCN (1L); Cohort 6.1 (expansion of Cohort 1a): Pre-treated patients MET GCN ≥ 10 without MET mutation (2L); Cohort 6.2 (expansion of Cohort 4): Pre-treated patients with MET mutation (2L); Cohort 7 (expansion of Cohort 5b): Treatment-naïve with MET mutation regardless of MET GCN (1L)

Eligibility Criteria

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

You may qualify if:

• Subjects with Stage IIIB or IV NSCLC (any histology) at the time of study entry
• Subjects with histologically or cytologically confirmed diagnosis of NSCLC that is:
• EGFR wt status (for exon 19 deletions and exon 21 L858R substitution mutations)
• and ALK rearrangement-negative
• and MET-mutation and/or amplification status (as defined in the protocol).
• For Cohorts 1a, 1b, 2, 3, 4 subjects must have failed one or two prior lines of systemic therapy for advanced disease (stage IIIB or IV NSCLC). For Cohort 6, subjects must have failed one prior line of systemic therapy for advanced disease (stage IIIB or IV NSCLC).
• For Cohorts 5a, 5b, and 7, subjects must not have received any systemic therapy for advanced disease (stage IIIB or IV NSCLC).
• Subjects with at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there was clear sign of progression since the irradiation.
• Subjects who recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] v 4.03). Subjects with any grade of alopecia were allowed to enter the study.
• Subjects with adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

You may not qualify if:

• Prior treatment with crizotinib, or any other MET or HGF inhibitor
• Characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations.
• Characterized ALK-positive rearrangement.
• Symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
• Clinically significant, uncontrolled heart diseases
• Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting capmatinib or subjects who had not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy ≤ 2 weeks prior to starting capmatinib or subjects who had not recovered from radiotherapy-related toxicities.
• Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting capmatinib was allowed.
• Receiving treatment with strong inducers of CYP3A4 and/or any enzyme-inducing anticonvulsant and could not be discontinued ≥ 1 week prior to the start of treatment with capmatinib and for the duration of the study.
• Receiving treatment with unstable or increasing doses of corticosteroids.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of capmatinib.
• Applicable to Cohorts 1-4 and Cohort 6 only: previous anticancer and investigational agents within 4 weeks or ≤ 5 × half-life of the agent (whichever was longer) before first dose of- capmatinib. If previous treatment was a monoclonal antibody, then the treatment must have been discontinued ≥ 4 weeks before first dose of capmatinib. If previous treatment was an oral targeted agent, then the treatment must have been discontinued ≥ 5 × half-life of the agent before the first dose of capmatinib.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 7 days after stopping treatment
• Sexually active males unless they used a condom during intercourse while taking drug and for 7 days after stopping treatment and should not father a child in this period.
• Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (95)

Pacific Shores Medical Group SC

Long Beach, California, 90813, United States

Location

University Of California Los Angeles Dept of Onc

Los Angeles, California, 90095, United States

Location

University of California Irvine Medical Center Chao Family Chao Family Comp Cancer Center

Orange, California, 92868, United States

Location

H Lee Moffitt Cancer Center and Research Institute .

Tampa, Florida, 33612, United States

Location

University of Iowa Hospitals and Clinics SC-3

Iowa City, Iowa, 52242, United States

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Massachusetts General Hospital MGH Cancer Center

Boston, Massachusetts, 02114, United States

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VA Ann Arbor Health System VA Ann Arbor Health System

Ann Arbor, Michigan, 48105, United States

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Mayo Clinic Rochester .

Rochester, Minnesota, 55905, United States

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Oregon Health and Science University SC

Portland, Oregon, 97239, United States

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Lehigh Valley Health Network SC

Allentown, Pennsylvania, 18103, United States

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Andrew and Patel Associates

Camp Hill, Pennsylvania, 17011, United States

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Mays Cancer Ctr Uthsa Mdacc SC-5

San Antonio, Texas, 78229, United States

Location

University of Utah / Huntsman Cancer Institute Oncology

Salt Lake City, Utah, 84103, United States

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Novartis Investigative Site

CABA, Buenos Aires, C1426ANZ, Argentina

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Novartis Investigative Site

Buenos Aires, Buenos Aires F.D., C1431FWO, Argentina

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Novartis Investigative Site

La Rioja, 5300, Argentina

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Novartis Investigative Site

Vienna, 1210, Austria

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Marseille, Bouches Du Rhone, 13915, France

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Novartis Investigative Site

Dijon, Cote D Or, 21034, France

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Novartis Investigative Site

Clermont-Ferrand, 63011, France

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Novartis Investigative Site

La Tronche, 38700, France

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Novartis Investigative Site

Lille, 59000, France

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Novartis Investigative Site

Marseille, 13273, France

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Novartis Investigative Site

Paris, 75970, France

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Novartis Investigative Site

Pierre-Bénite, 69495, France

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Novartis Investigative Site

Rennes, 35043, France

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Novartis Investigative Site

Strasbourg, 67091, France

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Novartis Investigative Site

Heidelberg, Baden-Wurttemberg, 69126, Germany

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Novartis Investigative Site

Berlin, 13125, Germany

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Cologne, 50937, Germany

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Frankfurt, 60590, Germany

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Novartis Investigative Site

Göttingen, 37075, Germany

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Novartis Investigative Site

Halle, 06120, Germany

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Novartis Investigative Site

Hamburg, 20251, Germany

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Novartis Investigative Site

Hanover, 30625, Germany

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Novartis Investigative Site

Homburg, 66421, Germany

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München, 81925, Germany

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Nuremberg, 90419, Germany

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Novartis Investigative Site

Ravensburg, 88214, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Ulm, 89081, Germany

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Novartis Investigative Site

Ramat Gan, 52621, Israel

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Novartis Investigative Site

Tel Aviv, 6423906, Israel

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Novartis Investigative Site

Bologna, BO, 40138, Italy

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Novartis Investigative Site

Brescia, BS, 25123, Italy

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Catania, CT, 95124, Italy

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Catanzaro, CZ, 88100, Italy

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Meldola, FC, 47014, Italy

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Florence, FI, 50134, Italy

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Novartis Investigative Site

Monza, MB, 20900, Italy

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Novartis Investigative Site

Milan, MI, 20141, Italy

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Novartis Investigative Site

Milan, MI, 20162, Italy

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Novartis Investigative Site

Modena, MO, 41124, Italy

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Novartis Investigative Site

Roma, RM, 00155, Italy

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Novartis Investigative Site

Verona, VR, 37126, Italy

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Novartis Investigative Site

Napoli, 80131, Italy

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Novartis Investigative Site

Nagoya, Aichi-ken, 464 8681, Japan

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Novartis Investigative Site

Nagoya, Aichi-ken, 466 8560, Japan

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Novartis Investigative Site

Fukuoka, Fukuoka, 811-1395, Japan

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Novartis Investigative Site

Akashi, Hyōgo, 673-8558, Japan

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Novartis Investigative Site

Sendai, Miyagi, 980 0873, Japan

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Novartis Investigative Site

Okayama, Okayama-ken, 700-8558, Japan

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Novartis Investigative Site

Ōsaka-sayama, Osaka, 589 8511, Japan

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Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

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Novartis Investigative Site

Koto Ku, Tokyo, 135 8550, Japan

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Novartis Investigative Site

Ube, Yamaguchi, 755-0241, Japan

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Novartis Investigative Site

El Achrafiyé, 166830, Lebanon

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Novartis Investigative Site

Mexico City, Mexico City, 14080, Mexico

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Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

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Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

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Novartis Investigative Site

Maastricht, 6229 HX, Netherlands

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Novartis Investigative Site

Rotterdam, 3015 GD, Netherlands

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Novartis Investigative Site

Oslo, NO 0424, Norway

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Novartis Investigative Site

Moscow, 109028, Russia

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Novartis Investigative Site

Saint Petersburg, 192148, Russia

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Novartis Investigative Site

Tambov, 392000, Russia

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Novartis Investigative Site

Singapore, 119228, Singapore

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Novartis Investigative Site

Singapore, 168583, Singapore

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Novartis Investigative Site

Bundang Gu, Gyeonggi-do, 13620, South Korea

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Novartis Investigative Site

Gyeonggi-do, Korea, 10408, South Korea

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Novartis Investigative Site

Seoul, 03080, South Korea

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Novartis Investigative Site

Seville, Andalusia, 41009, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

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Novartis Investigative Site

A Coruña, Galicia, 15006, Spain

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Novartis Investigative Site

Oviedo, Principality of Asturias, 33011, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Stockholm, SE-171 76, Sweden

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Novartis Investigative Site

Kaohsiung City, 82445, Taiwan

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Novartis Investigative Site

Taipei, 10002, Taiwan

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Novartis Investigative Site

Taoyuan District, 33305, Taiwan

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Novartis Investigative Site

Birmingham, B9 5SS, United Kingdom

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Novartis Investigative Site

London, W6 8RF, United Kingdom

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Related Publications (3)

• Wolf J, Hochmair M, Han JY, Reguart N, Souquet PJ, Smit EF, Orlov SV, Vansteenkiste J, Nishio M, de Jonge M, Akerley W, Garon EB, Groen HJM, Tan DSW, Seto T, Frampton GM, Robeva A, Carbini M, Le Mouhaer S, Yovine A, Boran A, Bossen C, Yang Y, Ji L, Fairchild L, Heist RS. Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial. Lancet Oncol. 2024 Oct;25(10):1357-1370. doi: 10.1016/S1470-2045(24)00441-8.

  PMID: 39362249 DERIVED

• Wolf J, Garon EB, Groen HJM, Tan DSW, Gilloteau I, Le Mouhaer S, Hampe M, Cai C, Chassot-Agostinho A, Reynolds M, Sherif B, Heist RS. Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study. Eur J Cancer. 2023 Apr;183:98-108. doi: 10.1016/j.ejca.2022.10.030. Epub 2022 Dec 10.

  PMID: 36822130 DERIVED

• Wolf J, Seto T, Han JY, Reguart N, Garon EB, Groen HJM, Tan DSW, Hida T, de Jonge M, Orlov SV, Smit EF, Souquet PJ, Vansteenkiste J, Hochmair M, Felip E, Nishio M, Thomas M, Ohashi K, Toyozawa R, Overbeck TR, de Marinis F, Kim TM, Laack E, Robeva A, Le Mouhaer S, Waldron-Lynch M, Sankaran B, Balbin OA, Cui X, Giovannini M, Akimov M, Heist RS; GEOMETRY mono-1 Investigators. Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Sep 3;383(10):944-957. doi: 10.1056/NEJMoa2002787.

  PMID: 32877583 DERIVED

Related Links

• For interim results on this study, please click the link below to the NovartisClinicalTrial.com website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Lung Neoplasms; Adenocarcinoma of Lung

Interventions

capmatinib

Condition Hierarchy (Ancestors)

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

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2015
• First Posted: April 10, 2015
• Study Start: June 11, 2015
• Primary Completion: April 12, 2023
• Study Completion: May 16, 2023
• Last Updated: March 20, 2024
• Results First Posted: March 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

IT (13); JP (10); TW (3); SE (1); US (13); DE (14); NO (1); FR (10); NL (4); ES (7); GB (2); SG (2); BE (1); KR (3); AR (3); AU (1); ME (1); IL (2); RU (3); LE (1)