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)

Conditions: Non-small Cell Lung Carcinoma (NSCLC); Melanoma; Bladder Cancer; Colorectal Cancer; Gastric Cancer; Ovarian Cancer

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.


Eligibility criteria:
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

Keywords: cancer oncology ccam biotherapeutics ltd immunomodulatory therapy cm-24 carcinoembryonic antigen-related cell adhesion molecule 1 (ceacam1) nsclc (adenocarcinoma) uveal acral mucosal cutaneous colorectal gastric ovarian bladder mk-6018-001