Non-small Cell Lung Carcinoma (NSCLC), Melanoma, Bladder Cancer, Colorectal Cancer, Gastric Cancer, Ovarian Cancer
Conditions
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
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.
Interventions
BIOLOGICALCM-24 (MK-6018)
humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion
BIOLOGICALPembrolizumab (MK-3475)
200 mg of Pembrolizumab by IV infusion
Sponsors
Famewave Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with Adverse Events (AEs) | From time of first dose until the end of follow-up (up to 123 weeks) |
| Number of participants discontinuing study drug due to AEs | From time of first dose until the end of follow-up (up to 105 weeks) |
| 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
| Measure | Time frame |
|---|---|
| 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. |
| Area under the plasma/serum concentration versus time curve from time zero to infinity (AUC 0-∞) | 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. |
| 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. |
| Time from ORR to disease progression or death (DOR) | From time of screening until the end of follow-up (up to 123 weeks) |
| 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) |
| 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. |
| 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. |
Countries
Israel, United States
Outcome results
None listed