A Study of Calderasib (MK-1084) Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004/KANDLELIT-004)

Official title

A Phase 3, Randomized, Double-blind, Multicenter Study of MK-1084 in Combination With Pembrolizumab Compared With Pembrolizumab Plus Placebo as Firstline Treatment of Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic NSCLC With PD-L1 TPS ≥50% (KANDLELIT-004)

Overview

This is a study evaluating the efficacy and safety of calderasib with pembrolizumab as first-line treatment in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with identified Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. There are two primary study hypotheses: Hypothesis 1: Combination of calderasib and pembrolizumab is superior to placebo plus pembrolizumab with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). Hypothesis 2: Combination of calderasib plus pembrolizumab is superior to placebo plus pembrolizumab with respect to overall survival (OS).

Interventions

• Drug Calderasib
  Oral tablets
• Other Placebo
  Oral tablets
• Biological Pembrolizumab
  IV infusion

Primary outcome measures

• Progression-Free Survival (PFS) [Time frame: Up to approximately 42 months]
• Overall Survival (OS) [Time frame: Up to approximately 56 months]

Secondary outcome measures (12)

• Objective Response Rate (ORR) [Time frame: Up to approximately 42 months]
• Duration of Response (DOR) [Time frame: Up to approximately 42 months]
• Number of Participants Who Experience One or More Adverse Event (AEs) [Time frame: Up to approximately 56 months]
• Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [Time frame: Up to approximately 56 months]
• Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score [Time frame: Baseline and Up to approximately 24 months]
• Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score [Time frame: Baseline and Up to approximately 24 months]
• Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Role Functioning (Items 6 and 7) Score [Time frame: Baseline and Up to approximately 24 months]
• Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score [Time frame: Baseline and Up to approximately 24 months]
• Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Cough (Item 31) Score [Time frame: Baseline and Up to approximately 24 months]
• Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13) Chest pain (Item 40) Score [Time frame: Baseline and Up to approximately 24 months]
• Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score [Time frame: Baseline and Up to approximately 24 months]
• Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score [Time frame: Baseline and Up to approximately 24 months]

Eligibility criteria

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion criteria

• Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
• Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8
• Provides an archival tumor tissue sample (≤5 years) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, PD-L1 status, and biomarker research
• If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to < Grade 1 or baseline
• If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)
• If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
• If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable

Exclusion criteria

• Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
• Has known history of, or active, neurologic paraneoplastic syndrome
• Has an active infection requiring systemic therapy, with exceptions
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
• Has one or more of the following ophthalmological findings/conditions: intraocular pressure >21 mmHg and/or any diagnosis of glaucoma, diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative disease
• Has received prior systemic anticancer therapy for their locally advanced or metastatic NSCLC
• Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention
• Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not required corticosteroids, and not have had radiation pneumonitis
• Has known active central nervous system metastases and/or carcinomatous meningitis
• Known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Is HIV-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has history of allogenic tissue/solid organ transplant
• Has not fully recovered from any effects of major surgical procedure

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 45 centers

• Anhui Provincial Cancer Hospital ( Site 3136) — Hefei
• Beijing Cancer hospital ( Site 3133) — Beijing
• Beijing Cancer hospital ( Site 3134) — Beijing
• Beijing Peking Union Medical College Hospital-pneumology department ( Site 3102) — Beijing
• Beijing Chest Hospital,Capital Medical University ( Site 3104) — Beijing
• Chongqing University Cancer Hospital ( Site 3119) — Chongqing
• Army Medical Center of People's Liberation Army ( Site 3142) — Chongqing
• Fujian Cancer Hospital ( Site 3127) — Fuzhou
• … and 37 more centers

Japan · 25 centers

Center list to be confirmed — check the primary protocol.

United States · 15 centers

• CBCC Global Research, Inc. ( Site 0123) — Bakersfield
• Beverly Hills Cancer Center ( Site 0116) — Beverly Hills
• Stamford Hospital ( Site 0136) — Stamford
• Mount Sinai Cancer Center ( Site 0137) — Miami Beach
• Orchard Healthcare Research Inc. ( Site 0115) — Skokie
• Truman Medical Center ( Site 0126) — Kansas City
• Cox Medical Center North ( Site 0133) — Springfield
• St. Vincent Frontier Cancer Center-Research ( Site 0105) — Billings
• … and 7 more centers

South Korea · 12 centers

Center list to be confirmed — check the primary protocol.

Ukraine · 11 centers

Center list to be confirmed — check the primary protocol.

Brazil · 10 centers

• Hospital Mario Penna ( Site 0436) — Belo Horizonte
• Hospital de Câncer de Recife ( Site 0447) — Recife
• Oncoclínica Oncologistas Associados ( Site 0441) — Teresina
• Liga Norte Riograndense Contra o Câncer ( Site 0439) — Natal
• Hospital de Caridade de Ijuí ( Site 0438) — Ijuí
• Hospital de Clínicas de Passo Fundo ( Site 0442) — Passo Fundo
• Irmandade da Santa Casa de Misericórdia de Porto Alegre-Centro Multidisciplinar de Pesquis — Porto Alegre
• Fundação Pio XII - Hospital de Câncer de Barretos-Unidade de Pesquisa Clínica ( Site 0437) — Barretos
• … and 2 more centers

Italy · 10 centers

Center list to be confirmed — check the primary protocol.

Georgia · 8 centers

Center list to be confirmed — check the primary protocol.

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 8 centers

Center list to be confirmed — check the primary protocol.

Greece · 7 centers

Center list to be confirmed — check the primary protocol.

Canada · 6 centers

• CancerCare Manitoba ( Site 0210) — Winnipeg
• QEII Health Sciences Centre - Victoria General Site-Dept. of Medical Oncology ( Site 0208) — Halifax
• Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0205) — Hamilton
• Sunnybrook Research Institute ( Site 0206) — Toronto
• St. Marys Hospital Center ( Site 0204) — Montreal
• Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-centre-d — Trois-Rivières

France · 6 centers

Center list to be confirmed — check the primary protocol.

Poland · 6 centers

Center list to be confirmed — check the primary protocol.

Romania · 6 centers

Center list to be confirmed — check the primary protocol.

Argentina · 5 centers

• AUSTRAL MEDICAL CENTER ( Site 0302) — CABA
• Centro Oncologico Korben ( Site 0304) — CABA
• Instituto de Investigaciones Clínicas Mar del Plata ( Site 0300) — Mar del Plata
• Fundacion Estudios Clinicos ( Site 0306) — Rosario
• Sanatorio Parque ( Site 0301) — Rosario

Bulgaria · 5 centers

• MBAL Uni Hospital-Department of Medical Oncology ( Site 1000) — Panagyurishte
• Multiprofile Hospital for Active Treatment SerdikaМЕD EOOD-Second Department of Medical On — Sofia
• MHAT - Heart and Brain ( Site 1006) — Pleven
• Medical Center Futuremeds ( Site 1007) — Plovdiv
• Complex Oncology Center - Plovdiv EOOD ( Site 1003) — Plovdiv

Chile · 5 centers

• Clinica Universidad Catolica del Maule-Oncology ( Site 0500) — Talca
• Orlandi Oncologia-Oncology ( Site 0503) — Santiago
• FALP-UIDO ( Site 0501) — Santiago
• Centro de Oncología de Precisión-Oncology ( Site 0502) — Santiago
• Bradfordhill-Clinical Area ( Site 0504) — Santiago

Australia · 4 centers

• Chris O'Brien Lifehouse ( Site 3000) — Camperdown
• Cancer Care Service Hervey Bay ( Site 3003) — Urraween
• Frankston Hospital ( Site 3002) — Frankston
• One Clinical Research ( Site 3001) — Nedlands

India · 4 centers

Center list to be confirmed — check the primary protocol.

Netherlands · 4 centers

Center list to be confirmed — check the primary protocol.

Philippines · 4 centers

Center list to be confirmed — check the primary protocol.

Germany · 3 centers

Center list to be confirmed — check the primary protocol.

Mexico · 3 centers

Center list to be confirmed — check the primary protocol.

Austria · 2 centers

• Medizinische Universität Graz-Klinische Abteilung für Pulmonologie ( Site 2401) — Graz
• Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 2400) — Vienna

United Kingdom · 2 centers

Center list to be confirmed — check the primary protocol.

New Zealand · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06345729 · 1084-004 · MK-1084-004 · U1111-1296-8093 · 2023-507776-42-00 · jRCT2031240213 · PHRR241128-007796 · KANDLELIT-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗