Clinical trial • Phase II • Oncology
MK-1084 for Non-squamous non-small cell lung cancer | KRAS G12C-mutant NSCLC
Phase II trial of MK-1084 for Non-squamous non-small cell lung cancer | KRAS G12C-mutant NSCLC.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Non-squamous non-small cell lung cancer | KRAS G12C-mutant NSCLC
- Trial Stage
- Phase II
- Drug Modality
- Small molecule | Monoclonal antibody
Key dates
- Initial CTIS Submission Date
- 17-10-2025
- First CTIS Authorization Date
- 24-02-2026
Trial design
Randomised, pemetrexed (intravenous infusion; max 1250 mg/m2 stated) and carboplatin (intravenous infusion; max 750 mg stated)-controlled, adaptive Phase II trial across 14 sites in Italy, Spain, Poland and others.
- Randomised
- Yes
- Comparator
- Pemetrexed (intravenous infusion; max 1250 mg/m2 stated) and Carboplatin (intravenous infusion; max 750 mg stated)
- Adaptive
- True, study described as a randomized phase 2 umbrella study with rolling arms of investigational agents ("Randomized Phase 2 Umbrella Study With Rolling Arms of Investigational Agents"). No further adaptive rules (e.g., interim analyses or stopping rules) are specified in the available record.
- Biomarker Stratified
- True, biomarker: KRAS G12C mutation
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 85
Eligibility
Recruits 85 No vulnerable population selected (isVulnerablePopulationSelected = false). Participants are adult patients; consent is obtained from participants. No assent/child consent procedures or other special vulnerable-population consent arrangements are described in the available record..
- Vulnerable Population
- No vulnerable population selected (isVulnerablePopulationSelected = false). Participants are adult patients; consent is obtained from participants. No assent/child consent procedures or other special vulnerable-population consent arrangements are described in the available record.
Inclusion criteria
- {"criterion_text":"- Has histologically or cytologically confirmed diagnosis of advanced or metastatic nonsquamous Non-Small Cell Lung Cancer (NSCLC)\n- Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations\n- Can provide an archival tumor tissue sample or newly obtained core, incisional, excisional biopsy of a tumor lesion not previously irradiated\n- Has recovered to ≤Grade 1 or baseline from any Adverse events (AEs) due to previous anticancer therapies and/or ≤Grade 2 neuropathy and/or endocrine-related AEs adequately treated with hormone replacement\n- Has well controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART) if HIV-infected\n- Has undetectable hepatitis B (HBV) viral load and have received HBV antiviral therapy for at least 4 weeks if hepatitis B surface antigen (HBsAg) positive\n- Has undetectable hepatitis C (HCV) viral load if HCV-infected"}
Exclusion criteria
- {"criterion_text":"- Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements\n- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention\n- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years\n- Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis\n- Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed\n- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease\n- Has a history of stem cell/solid organ transplant\n- Has not adequately recovered from major surgery or has ongoing surgical complications\n- Has HIV-infection with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease\n- Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease\n- Has uncontrolled, clinically significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval corrected for heart rate by Fridericia's formula (QTcF) interval to >470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention\n- Has received prior systemic anticancer therapy for advanced or metastatic NSCLC\n- Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE) (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis\n- Has received previous treatment with an agent targeting KRAS\n- Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) and has not recovered to grade ≤ 1 or baseline from AE associated with anticancer therapy before allocation/randomization\n- Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Percentage of Participants with a Dose Limiting Toxicity (DLT)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Percentage of Participants who Experience at Least One Adverse Event (AE)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Percentage of Participants who Discontinue Study Intervention Due to an AE","definition_or_measurement_approach":""}
- {"endpoint_text":"- Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR)","definition_or_measurement_approach":"ORR measured per RECIST 1.1 with assessment by Blinded Independent Central Review (BICR)"}
Secondary endpoints
- {"endpoint_text":"- Duration of Response (DOR) per RECIST 1.1 as assessed by BICR","definition_or_measurement_approach":"DOR measured per RECIST 1.1 as assessed by BICR"}
- {"endpoint_text":"- Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR","definition_or_measurement_approach":"PFS measured per RECIST 1.1 as assessed by BICR"}
- {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Area Under the Concentration-Time Curve (AUC) for MK-1084","definition_or_measurement_approach":"Pharmacokinetic parameter AUC for MK-1084"}
- {"endpoint_text":"- Maximum Concentration (Cmax) of MK-1084","definition_or_measurement_approach":"Pharmacokinetic parameter Cmax for MK-1084"}
- {"endpoint_text":"- Trough Concentration (Ctrough) of MK-1084","definition_or_measurement_approach":"Pharmacokinetic parameter Ctrough for MK-1084"}
Recruitment
- Planned Sample Size
- 85
- Recruitment Window Months
- 69
- Consent Approach
- Informed consent is obtained from participants via country-specific informed consent forms. Country-specific ICF documents are listed for Finland, Italy, Spain, Poland, Netherlands (languages indicated in document titles: English, Italian, Spanish, Polish, Dutch, Finnish). Consent appears to be provided by the participant; no separate assent or minor/parent consent procedures are described in the available record.
Geography
- Total Number Of Sites
- 14
- Total Number Of Participants
- 43
Italy
- Earliest CTIS Part Ii Submission Date
- 08-11-2025
- Latest Decision Or Authorization Date
- 25-02-2026
- Processing Time Days
- 109
- Number Of Sites
- 3
- Number Of Participants
- 6
Sites
- Site Name
- Azienda Ospedaliera S Giovanni Addolorata
- Department Name
- Unità Clinica di Fase I di Oncologia, Ematologia, Medicina Nucleare
- Principal Investigator Name
- Antonio Lugini
- Principal Investigator Email
- alugini@hsangiovanni.roma.it
- Contact Person Name
- Antonio Lugini
- Contact Person Email
- alugini@hsangiovanni.roma.it
- Site Name
- Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
- Department Name
- Unità Clinica di Fase I di Oncologia, Ematologia, Medicina Nucleare
- Principal Investigator Name
- Angelo Delmonte
- Principal Investigator Email
- angelo.delmonte@irst.emr.it
- Contact Person Name
- Angelo Delmonte
- Contact Person Email
- angelo.delmonte@irst.emr.it
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- Oncologia Medica 1
- Principal Investigator Name
- Marta Brambilla
- Principal Investigator Email
- marta.brambilla@istitutotumori.mi.it
- Contact Person Name
- Marta Brambilla
- Contact Person Email
- marta.brambilla@istitutotumori.mi.it
Spain
- Earliest CTIS Part Ii Submission Date
- 13-01-2026
- Latest Decision Or Authorization Date
- 02-03-2026
- Processing Time Days
- 48
- Number Of Sites
- 2
- Number Of Participants
- 12
Sites
- Site Name
- Hospital Universitario Virgen De La Macarena
- Department Name
- Medical Oncology
- Principal Investigator Name
- David Vicente Baz
- Principal Investigator Email
- david.vbaz@gmail.com
- Contact Person Name
- David Vicente Baz
- Contact Person Email
- david.vbaz@gmail.com
- Site Name
- Hospital Universitario Quironsalud Madrid
- Department Name
- Medical Oncology
- Principal Investigator Name
- Belén Rubio Viqueira
- Principal Investigator Email
- ensayosoncologia.mad@quironsalud.es
- Contact Person Name
- Belén Rubio Viqueira
- Contact Person Email
- ensayosoncologia.mad@quironsalud.es
Poland
- Earliest CTIS Part Ii Submission Date
- 22-01-2026
- Latest Decision Or Authorization Date
- 26-02-2026
- Processing Time Days
- 35
- Number Of Sites
- 3
- Number Of Participants
- 9
Sites
- Site Name
- Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
- Department Name
- Klinika Nowotworów Płuca i Klatki Piersiowej
- Principal Investigator Name
- Sylwia Tabor
- Principal Investigator Email
- paulina.kukwa@nio.gov.pl
- Contact Person Name
- Sylwia Tabor
- Contact Person Email
- paulina.kukwa@nio.gov.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Centrum Wsparcia Badań Klinicznych UCK, Ośrodek Badań Klinicznych Wczesnych Faz
- Principal Investigator Name
- Rafał Dziadziuszko
- Principal Investigator Email
- obkwf@uck.gda.pl
- Contact Person Name
- Rafał Dziadziuszko
- Contact Person Email
- obkwf@uck.gda.pl
- Site Name
- Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie
- Department Name
- Oddział Onkologii Klinicznej z Pododdziałem Chemioterapii Jednodniowej
- Principal Investigator Name
- Mariusz Kwiatkowski
- Principal Investigator Email
- sekretariat.odch@swk.med.pl
- Contact Person Name
- Mariusz Kwiatkowski
- Contact Person Email
- sekretariat.odch@swk.med.pl
Netherlands
- Earliest CTIS Part Ii Submission Date
- 19-02-2026
- Latest Decision Or Authorization Date
- 02-03-2026
- Processing Time Days
- 11
- Number Of Sites
- 2
- Number Of Participants
- 7
Sites
- Site Name
- Deventer Ziekenhuis
- Department Name
- Department of Pulmonology
- Principal Investigator Name
- Rogier C. Boshuizen
- Principal Investigator Email
- researchoncologie@dz.nl
- Contact Person Name
- Rogier C. Boshuizen
- Contact Person Email
- researchoncologie@dz.nl
- Site Name
- Leids Universitair Medisch Centrum (LUMC)
- Department Name
- Department of Pulmonary Diseases
- Principal Investigator Name
- Egbert Frederik Smit
- Principal Investigator Email
- e.f.smit@lumc.nl
- Contact Person Name
- Egbert Frederik Smit
- Contact Person Email
- e.f.smit@lumc.nl
Finland
- Earliest CTIS Part Ii Submission Date
- 30-01-2026
- Latest Decision Or Authorization Date
- 17-03-2026
- Processing Time Days
- 46
- Number Of Sites
- 4
- Number Of Participants
- 9
Sites
- Site Name
- HUS-yhtymae
- Department Name
- Helsinki University Hospital - Comprehensive Cancer Center
- Principal Investigator Name
- Ilkka Liikanen
- Principal Investigator Email
- ilkka.liikanen@hus.fi
- Contact Person Name
- Ilkka Liikanen
- Contact Person Email
- ilkka.liikanen@hus.fi
- Site Name
- Vaasa Central Hospital
- Department Name
- Department of Clinical Oncology
- Principal Investigator Name
- Ravichandra Ravi
- Principal Investigator Email
- ravichandra.ravi@ovph.fi
- Contact Person Name
- Ravichandra Ravi
- Contact Person Email
- ravichandra.ravi@ovph.fi
- Site Name
- Turku University Hospital
- Department Name
- Department of pulmonary diseases
- Principal Investigator Name
- Maria Silvoniemi
- Principal Investigator Email
- maria.silvoniemi@varha.fi
- Contact Person Name
- Maria Silvoniemi
- Contact Person Email
- maria.silvoniemi@varha.fi
- Site Name
- Kuopio University Hospital
- Department Name
- Oncology
- Principal Investigator Name
- Okko Kääriäinen
- Principal Investigator Email
- okko.kaariainen@pshyvinvointialue.fi
- Contact Person Name
- Okko Kääriäinen
- Contact Person Email
- okko.kaariainen@pshyvinvointialue.fi
Sponsor
Primary sponsor
- Full Name
- Merck Sharp & Dohme LLC
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Pharmaceutical Product Development LLC
- Responsibilities
- sponsorDuties codes: 4
- Name
- Syneos Health Clinique Inc.
- Responsibilities
- sponsorDuties codes: 4
- Name
- Bioclinica Inc.
- Responsibilities
- Central imaging
- Name
- Parexel International Corp.
- Responsibilities
- EUB services (call center and medical services)
- Name
- Almac Clinical Technologies LLC
- Responsibilities
- sponsorDuties codes: 3
- Name
- PPD Global Central Labs
- Responsibilities
- sponsorDuties codes: 4
Third parties
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central imaging","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- MK-1084
- Active Substance
- MK-1084
- Modality
- Small molecule
- Routes Of Administration
- ORAL / ORAL USE
- Route
- Oral
- Authorisation Status
- Investigational
- Investigational Product Name
- KEYTRUDA (pembrolizumab)
- Active Substance
- PEMBROLIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- Intravenous infusion
- Authorisation Status
- Authorised (marketing authorisation EU/1/15/1024/002)
- Maximum Dose
- 400 mg (max daily amount stated)
- Investigational Product Name
- CETUXIMAB
- Active Substance
- CETUXIMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- Intravenous infusion
- Authorisation Status
- Authorised
- Maximum Dose
- 1250 mg (max daily amount stated)
- Investigational Product Name
- CARBOPLATIN
- Active Substance
- CARBOPLATIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- Intravenous infusion
- Authorisation Status
- Authorised
- Maximum Dose
- 750 mg (max daily amount stated)
- Investigational Product Name
- PEMETREXED (pemetrexed disodium)
- Active Substance
- PEMETREXED DISODIUM
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- Intravenous infusion
- Authorisation Status
- Authorised
- Maximum Dose
- 1250 mg/m2 (max daily amount stated)
- Combination Treatment
- Yes
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