A Clinical Study of MK-1084 and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007)
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT07190248
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Researchers want to learn if the study medicines MK-1084 and subcutaneous (SC) pembrolizumab can be used to treat non-small cell lung cancer (NSCLC) when given together. MK-1084 is a targeted therapy for the KRAS G12C mutation.
The goal of this study is to learn if people who receive MK-1084 with SC pembrolizumab live longer without the cancer growing or spreading than in people who receive SC pembrolizumab with chemotherapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 675
The main inclusion criteria include but are not limited to the following:
- Has nonsquamous NSCLC (Stage IIIB, Stage IIIC) not eligible for curative resection or chemoradiation or Stage IV: M1a, M1b, or M1c
- If human immunodeficiency virus (HIV) positive, must have well controlled HIV on antiretroviral therapy (ART)
The main exclusion criteria include but are not limited to the following:
- Has diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
- Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea)
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- Has a gastrointestinal disorder affecting absorption
- Is HIV positive and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Has received prior systemic anticancer therapy for their advanced or metastatic NSCLC
- Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has active autoimmune disease that has required systemic treatment in the past 2 years
- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has active infection requiring systemic therapy except those specified by protocol
- Has history of stem cell/solid organ transplant
- Has not adequately recovered from major surgery or has ongoing surgical complications
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MK-1084 + Pembrolizumab (+) Berahyaluronidase alfa MK-1084 Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) plus MK-1084 100 mg once daily until discontinuation criterion is met. MK-1084 + Pembrolizumab (+) Berahyaluronidase alfa Pembrolizumab (+) Berahyaluronidase alfa Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) plus MK-1084 100 mg once daily until discontinuation criterion is met. Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy Pembrolizumab (+) Berahyaluronidase alfa Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m\^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m\^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks). Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy Pemetrexed Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m\^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m\^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks). Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy Cisplatin Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m\^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m\^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks). Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy Carboplatin Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m\^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m\^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks).
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) in Participants with Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1% Up to approximately 48 months PFS is defined as the time from randomization until either documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. PFS as determined by blinded independent central review (BICR) will be presented.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) Up to approximately 48 months For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
Number of Participants Who Experienced One or More Adverse Events (AEs) Up to approximately 81 months An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be presented.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to approximately 81 months An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be presented.
Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire (EORTC QLQ-LC13) Baseline and up to approximately 81 months The EORTC QLQ-C13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). The change from baseline in the score of EORTC QLQ-C13 Item 31 will be presented. A higher score indicates more frequent coughing.
Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 Baseline and up to approximately 81 months The EORTC QLQ-C13 is lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). The change from baseline in the score of EORTC QLQ-C13 Item 40 will be presented. A higher score indicates a worse level of chest pain.
Change from Baseline in Global Health Status/Quality of Life (GHS/QoL) (Items 29, 30) on the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30) Baseline and up to approximately 81 months The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. Higher scores indicate a better overall health status.
Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 Baseline and up to approximately 81 months The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). The change from baseline in the score of EORTC QLQ-C30 Item 8 will be presented. A higher score indicates a worse level of dyspnea.
PFS in All Participants Up to approximately 48 months PFS is defined as the time from randomization until either documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first. PFS as determined by BICR will be presented.
Overall Survival (OS) in Participants with PD-L1 TPS ≥1% Up to approximately 62 months OS is defined as the time from randomization to death due to any cause.
OS in Participants in All Participants Up to approximately 62 months OS is defined as the time from randomization to death due to any cause.
Overall Response Rate (ORR) in All Participants Up to approximately 48 months ORR is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) per RECIST1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
ORR in Participants with PD-L1 TPS ≥1% Up to approximately 48 months ORR is defined as the percentage of participants with CR or PR per RECIST1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
Time to Deterioration (TTD) in GHS/QoL (Items 29, 30) on the EORTC QLQ-C30 Baseline and up to approximately 81 months TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in global health status (GHS) and quality of life (QoL) (EORTC QLQ-C30 Items 29 and 30) score. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in GHS and QoL, will be presented. A longer TTD indicates a better outcome.
TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 Baseline and up to approximately 81 months TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in dyspnea (EORTC QLQ-C30 Item 8) score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in dyspnea score, will be presented. A longer TTD indicates a better outcome.
TTD in Cough Score (Item 31) on the EORTC QLQ-LC13 Baseline and up to approximately 81 months TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in cough (EORTC QLQ-C13 Item 31) score. The EORTC QLQ-C13 is lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in cough score, will be presented. A longer TTD indicates a better outcome.
TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 Baseline and up to approximately 81 months TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in chest pain (EORTC QLQ-C13 Item 40) score. The EORTC QLQ-C13 is lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline chest pain score, will be presented. A longer TTD indicates a better outcome.