Clinical trial NCT02346955: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-small Cell Lung Carcinoma (NSCLC)
Melanoma
Bladder Cancer
Colorectal Cancer
Gastric Cancer
Ovarian Cancer
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
Lead sponsor: KitovPharma
Sponsor class: UNKNOWN
First posted: 2015-01-27
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of participants with Adverse Events (AEs)
timeFrame: From time of first dose until the end of follow-up (up to 123 weeks)
measure: Number of participants discontinuing study drug due to AEs
timeFrame: From time of first dose until the end of follow-up (up to 105 weeks)
measure: Number of participants with a Dose Limiting Toxicity (DLT)
timeFrame: From time of first dose until the end of follow-up (up to 12 weeks)
Secondary outcomes:
measure: Maximum drug concentration in serum/plasma (Cmax)
timeFrame: 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.
measure: Time to reach Cmax in serum/plasma (Tmax)
timeFrame: 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.
measure: Terminal-phase elimination half-life in serum/plasma (t1/2)
timeFrame: 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.
measure: Area under the plasma/serum concentration versus time curve from time zero to the last measured time (AUC 0-T)
timeFrame: 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.
measure: Area under the plasma/serum concentration versus time curve from time zero to infinity (AUC 0-∞)
timeFrame: 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.
measure: Objective Response Rate (ORR) defined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
timeFrame: From time of screening until the end of follow-up (up to 123 weeks)
measure: Time from ORR to disease progression or death (DOR)
timeFrame: From time of screening until the end of follow-up (up to 123 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Call for Information (Investigational Site 0003)
state: California
city: New Haven
country: United States
facility: Call for Information (Investigational Site 0004)
state: Connecticut
city: Hod Hasharon
country: Israel
facility: Merck Sharp & Dohme Co. Ltd.
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: