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)

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02346955
• Other study ID #: 6018-001
• Secondary ID: CB-24-01MK-6018-
• Status: Terminated
• Phase: Phase 1
• Start date: February 2015
• Est. completion date: February 2017

Study information

• Verified date: August 2020
• Source: Kitov Pharma Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Gastric Cancer
• Melanoma
• Non-small Cell Lung Carcinoma (NSCLC)
• Ovarian Cancer

Intervention

Biological:
• CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
• Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion

Locations

Country	Name	City	State
Israel	Merck Sharp & Dohme Co. Ltd.	Hod Hasharon
United States	Call for Information (Investigational Site 0003)	Los Angeles	California
United States	Call for Information (Investigational Site 0004)	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Famewave Ltd.

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs)		From time of first dose until the end of follow-up (up to 123 weeks)
Primary	Number of participants discontinuing study drug due to AEs		From time of first dose until the end of follow-up (up to 105 weeks)
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Area under the plasma/serum concentration versus time curve from time zero to infinity (AUC 0-8)		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.
Secondary	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)
Secondary	Time from ORR to disease progression or death (DOR)		From time of screening until the end of follow-up (up to 123 weeks)