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)

A Phase 1, Open-Label, Multicenter, Multi-Dose Escalation Study of CM-24 (MK-6018) as Monotherapy and In Combination With Pembrolizumab (MK-3475) in Subjects With Selected Advanced or Recurrent Malignancies

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.

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