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)

NCT ID: NCT02346955

Last Updated: 2020-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-28

Study Completion Date

2017-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

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.

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

Pembrolizumab (MK-3475)

Intervention Type BIOLOGICAL

200 mg of Pembrolizumab by IV infusion

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.

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

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.

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

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.

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

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).

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

Pembrolizumab (MK-3475)

Intervention Type BIOLOGICAL

200 mg of Pembrolizumab by IV infusion

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).

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

Pembrolizumab (MK-3475)

Intervention Type BIOLOGICAL

200 mg of Pembrolizumab by IV infusion

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).

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

Pembrolizumab (MK-3475)

Intervention Type BIOLOGICAL

200 mg of Pembrolizumab by IV infusion

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).

Group Type EXPERIMENTAL

CM-24 (MK-6018)

Intervention Type BIOLOGICAL

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

Pembrolizumab (MK-3475)

Intervention Type BIOLOGICAL

200 mg of Pembrolizumab by IV infusion

Interventions

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CM-24 (MK-6018)

humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

Intervention Type BIOLOGICAL

Pembrolizumab (MK-3475)

200 mg of Pembrolizumab by IV infusion

Intervention Type BIOLOGICAL

Other Intervention Names

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Anti-CEACAM1 KEYTRUDA®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Famewave Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Call for Information (Investigational Site 0003)

Los Angeles, California, United States

Site Status

Call for Information (Investigational Site 0004)

New Haven, Connecticut, United States

Site Status

Merck Sharp & Dohme Co. Ltd.

Hod HaSharon, , Israel

Site Status

Countries

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United States Israel

Other Identifiers

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CB-24-01

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-6018-001

Identifier Type: OTHER

Identifier Source: secondary_id

6018-001

Identifier Type: -

Identifier Source: org_study_id

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