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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)

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ClinicalTrials.gov Identifier: NCT02346955
Recruitment Status : Terminated
First Posted : January 27, 2015
Last Update Posted : March 16, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Carcinoma (NSCLC) Melanoma Bladder Cancer Colorectal Cancer Gastric Cancer Ovarian Cancer Biological: CM-24 (MK-6018) Biological: Pembrolizumab (MK-3475) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : February 2015
Actual Primary Completion Date : February 2017
Actual Study Completion Date : February 2017


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 Name: 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 Name: Anti-CEACAM1

Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: Anti-CEACAM1

Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Name: 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 Name: Anti-CEACAM1

Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Name: 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 Name: Anti-CEACAM1

Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Name: 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 Name: Anti-CEACAM1

Biological: Pembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Other Name: KEYTRUDA®




Primary Outcome Measures :
  1. Number of participants with Adverse Events (AEs) [ Time Frame: From time of first dose until the end of follow-up (up to 123 weeks) ]
  2. 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) ]
  3. 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) ]

Secondary Outcome Measures :
  1. 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. ]
  2. 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. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]
  6. 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) ]
  7. 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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02346955


Locations
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United States, California
Call for Information (Investigational Site 0003)
Los Angeles, California, United States, 90095
United States, Connecticut
Call for Information (Investigational Site 0004)
New Haven, Connecticut, United States, 06513
Israel
Merck Sharp & Dohme Co. Ltd.
Hod Hasharon, Israel
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02346955     History of Changes
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 )
First Posted: January 27, 2015    Key Record Dates
Last Update Posted: March 16, 2017
Last Verified: March 2017
Keywords provided by Merck Sharp & Dohme Corp.:
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
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Neoplasms
Neoplasms by Site
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents