Study of CM-24 (MK-6018) Alone and In Combination With Pembrolizumab (MK-3475) in Participants With Selected Advanced or Recurrent Malignancies (MK-6018-001)
Phase 1
Terminated
- Conditions
- Bladder CancerOvarian CancerNon-small Cell Lung Carcinoma (NSCLC)MelanomaColorectal CancerGastric Cancer
- Registration Number
- NCT02346955
- Lead Sponsor
- Famewave Ltd.
- Brief Summary
The purpose of this study is to evaluate the safety and tolerability of humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 (CM-24 \[MK-6018\]), administered intravenously as monotherapy and in combination with Pembrolizumab (MK-3475), in participants with selected advanced or recurrent malignancies. Escalating multiple doses will be evaluated to determine the recommended dose for Phase 2 clinical studies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 27
Inclusion Criteria
- Males and females ≥18 years of age
- Participants in the Dose Escalation portion must have one of the following advanced or recurrent malignancies: gastrointestinal (colorectal or gastric); ovarian; melanoma; non-small cell lung adenocarcinoma; or bladder.
- Participants in the Monotherapy Expansion Cohort must have one of the following advanced or recurrent malignancies: cutaneous melanoma showing primary progression following treatment with an anti-programmed cell death (PD) or anti-PDL1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III.
- Participants in the Combination Expansion Cohorts must have one of the following advanced or recurrent malignancies: non-small cell lung adenocarcinoma or cutaneous melanoma showing primary progression following treatment with an anti-PD1 or anti-PD-L1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III.
- Melanoma with BRAF V600E or V600K mutation-positive melanoma must have progressed on, or were intolerant to, prior BRAF- or MEK-inhibitor therapy
- Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with progressing or new tumors since last antitumor therapy
- Must have adequate hematologic, renal, and liver function
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Females must not be pregnant (negative human chorionic gonadotropin test within 72 hours prior to receiving the first dose of study medication) or breastfeeding
- Women of childbearing potential and male participants must agree to use adequate contraception throughout the study and for up to 180 days after study treatment
- An estimated life expectancy of at least 3 months
- Must consent to provide an archival tumor biopsy sample at any time point from screening to study exit
- Must consent to allow the acquisition of new tissue biopsy samples during the study
Exclusion Criteria
- History of severe hypersensitivity reactions or immune related adverse events to other monoclonal antibodies
- History of other active malignancy within the prior 2 years
- History of insulin-dependent or uncontrolled Diabetes Mellitus
- History of inflammatory bowel disease
- Autoimmune disorders
- Known HIV and/or Hepatitis B or C infections
- Known systemic bleeding or platelet disorder
- Receipt of live vaccines with 4 weeks (28 days) of study
- History or evidence of non-infectious pneumonitis that required steroids or current pneumonitis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Number of participants with Adverse Events (AEs) From time of first dose until the end of follow-up (up to 123 weeks) Number of participants discontinuing study drug due to AEs From time of first dose until the end of follow-up (up to 105 weeks) Number of participants with a Dose Limiting Toxicity (DLT) From time of first dose until the end of follow-up (up to 12 weeks)
- Secondary Outcome Measures
Name Time Method Maximum drug concentration in serum/plasma (Cmax) For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion. Time to reach Cmax in serum/plasma (Tmax) For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion. Terminal-phase elimination half-life in serum/plasma (t1/2) For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion. Area under the plasma/serum concentration versus time curve from time zero to infinity (AUC 0-∞) For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion. Area under the plasma/serum concentration versus time curve from time zero to the last measured time (AUC 0-T) For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion. Objective Response Rate (ORR) defined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria From time of screening until the end of follow-up (up to 123 weeks) Time from ORR to disease progression or death (DOR) From time of screening until the end of follow-up (up to 123 weeks)
Trial Locations
- Locations (3)
Call for Information (Investigational Site 0003)
🇺🇸Los Angeles, California, United States
Call for Information (Investigational Site 0004)
🇺🇸New Haven, Connecticut, United States
Merck Sharp & Dohme Co. Ltd.
🇮🇱Hod Hasharon, Israel
Call for Information (Investigational Site 0003)🇺🇸Los Angeles, California, United States