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)

August 25, 2020 updated by: Famewave Ltd.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Hod Hasharon, Israel
        • Merck Sharp & Dohme Co. Ltd.
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Call for Information (Investigational Site 0003)
    • Connecticut
      • New Haven, Connecticut, United States, 06513
        • Call for Information (Investigational Site 0004)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A Monotherapy Dose Escalation
Participants will be enrolled in a staggered manner starting at a dose of 0.01 mg/kg of CM-24 (MK-6018) and continuing to 0.03, 0.1, 0.3, 1.0, 3.0, and 10 mg/kg to determine the recommended Phase 2 dose (RP2D). The dose will be escalated after a 6- to 8-week DLT window. Participants will be treated for 12 weeks during Cycle 1. Afterwards participants with clinical benefit and no dose-limiting toxicites (DLTs) are treated for up to 6 cycles.
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Experimental: Cohort B Combination Dose Escalation
Participants will be enrolled at the recommended phase 2 dose (RP2D) of CM-24 (MK-6018), determined by escalation studies, minus 1 dose level of MK-6018 in combination with a fixed dose of 200 mg pembrolizumab. Participants will be escalated to the RP2D of MK-6018 + 200 mg pembrolizumab. If the RP2D of MK-6018 + 200 mg pembrolizumab is not tolerated, the dose of MK-6018 will be de-escalated but will not fall below 1 mg/kg. Participants will be treated for 6 weeks during Cycle 1 and 2. Afterwards participants with clinical benefit and no DLTs are treated for up to 35 cycles.
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Names:
  • KEYTRUDA®
Experimental: Cohort C Monotherapy Expansion
Participants with advanced or recurrent cutaneous melanoma will be enrolled and treated at the recommended phase 2 dose of CM-24 (MK-6018) for up to 17 cycles.
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Experimental: Cohort D Monotherapy Expansion
Participants with advanced or recurrent colorectal cancer will be enrolled and treated at the recommended phase 2 dose of CM-24 (MK-6018) for up to 17 cycles.
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Experimental: Cohort E Monotherapy Expansion
Participants with advanced or recurrent gastric cancer will be enrolled and treated at the recommended phase 2 dose of CM-24 (MK-6018) for up to 17 cycles.
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Experimental: Cohort C1 Combination Expansion
Participants with advanced or recurrent cutaneous melanoma will be enrolled and treated at the recommended phase 2 dose of CM-24+ 200 mg of Pembrolizumab for up to 17 cycles and may continue to receive 200 mg of Pembrolizumab as monotherapy for up to an additional 18 cycles (up to 35 total cycles).
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Names:
  • KEYTRUDA®
Experimental: Cohort D1 Combination Expansion
Participants with advanced or recurrent colorectal cancer will be enrolled and treated at the recommended phase 2 dose of CM-24+ 200 mg of Pembrolizumab for up to 17 cycles and may continue to receive 200 mg of Pembrolizumab as monotherapy for up to an additional 18 cycles (up to 35 total cycles).
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Names:
  • KEYTRUDA®
Experimental: Cohort E1 Combination Expansion
Participants with advanced or recurrent gastric cancer will be enrolled and treated at the recommended phase 2 dose of CM-24+ 200 mg of Pembrolizumab for up to 17 cycles and may continue to receive 200 mg of Pembrolizumab as monotherapy for up to an additional 18 cycles (up to 35 total cycles).
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Names:
  • KEYTRUDA®
Experimental: Cohort F Combination Expansion
Participants with advanced or recurrent non-small cell lung adenocarcinoma will be enrolled and treated at the recommended phase 2 dose of CM-24+ 200 mg of Pembrolizumab for up to 17 cycles and may continue to receive 200 mg of Pembrolizumab as monotherapy for up to an additional 18 cycles (up to 35 total cycles).
Biological: CM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
Other Names:
  • Anti-CEACAM1
Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Names:
  • KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with Adverse Events (AEs)
Time Frame: From time of first dose until the end of follow-up (up to 123 weeks)
From time of first dose until the end of follow-up (up to 123 weeks)
Number of participants discontinuing study drug due to AEs
Time Frame: From time of first dose until the end of follow-up (up to 105 weeks)
From time of first dose until the end of follow-up (up to 105 weeks)
Number of participants with a Dose Limiting Toxicity (DLT)
Time Frame: From time of first dose until the end of follow-up (up to 12 weeks)
From time of first dose until the end of follow-up (up to 12 weeks)

Secondary Outcome Measures

Outcome Measure
Time Frame
Maximum drug concentration in serum/plasma (Cmax)
Time Frame: 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.
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)
Time Frame: 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.
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)
Time Frame: 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.
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)
Time Frame: 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.
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-∞)
Time Frame: 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.
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
Time Frame: From time of screening until the end of follow-up (up to 123 weeks)
From time of screening until the end of follow-up (up to 123 weeks)
Time from ORR to disease progression or death (DOR)
Time Frame: From time of screening until the end of follow-up (up to 123 weeks)
From time of screening until the end of follow-up (up to 123 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Famewave Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2015

Primary Completion (Actual)

February 1, 2017

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

December 9, 2014

First Submitted That Met QC Criteria

January 21, 2015

First Posted (Estimate)

January 27, 2015

Study Record Updates

Last Update Posted (Actual)

August 27, 2020

Last Update Submitted That Met QC Criteria

August 25, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6018-001
  • CB-24-01 (Registry Identifier: prior cCAM Biotherapeutics Ltd Protocol Number)
  • MK-6018-001 (Other Identifier: Merck Registration Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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