A Phase I, Open-Label, Dose Finding Study of CC-90002, a Monoclonal Antibody Directed Against CD47, in Subjects With Advanced Solid and Hematologic Cancers
Overview
- Phase
- Phase 1
- Intervention
- CC-90002
- Conditions
- Hematologic Neoplasms
- Sponsor
- Celgene
- Enrollment
- 60
- Locations
- 13
- Primary Endpoint
- Dose-Limiting Toxicity (DLT)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
CC-90002-ST -001 is an open-label, Phase 1, dose escalation clinical study in subjects with advanced, refractory solid and hematologic cancers.
Detailed Description
CC-90002-ST-001 is an open-label, Phase 1, dose escalation, first in human (FIH) clinical study of CC-90002, administered by intravenous (IV) infusion, in subjects with advanced, refractory solid and hematologic cancers. The study will be conducted in two parts. Part A dose escalation phase will explore escalating dose cohorts of the study drug CC-90002. Part B dose escalation will explore escalating doses of CC-90002 in combination with rituximab in subjects with CD20-positive NHL.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women, 18 years or older, with advanced, relapsed or refractory solid tumors, Multiple Myeloma (MM) or non-Hodgkin's lymphoma (NHL) in Part A. In Part B, relapsed and/or refractory CD20-positive NHL subjects only.
- •At least one site of measurable disease in subjects with solid tumors and NHL.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or
- •Subjects must have adequate hematopoietic, liver, renal and coagulation function as assessed by specific laboratory criteria.
- •Females and males must agree to contraceptive methods and avoid conceiving throughout the study, and for up to 8 weeks following the last dose of CC-
- •If participating in Part B, females of child bearing potential should continue to use effective contraceptive methods for 12 months following treatment with rituximab
Exclusion Criteria
- •High grade lymphomas (Burkitts or lymphoblastic), plasma cell leukemia.
- •High grade, rapidly proliferative solid tumors (eg, small cell lung cancer, germ cell tumors, neuroblastoma) with extensive tumor burden.
- •Symptomatic central nervous system involvement.
- •Impaired cardiac function or clinically significant cardiac disease.
- •Prior Red blood cell (RBC) transfusion \< 3 months prior to starting CC-90002 (Part A only).
- •Prior autologous stem cell transplant ≤ 3 months prior to starting CC-
- •Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-
- •Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks prior to starting CC-90002, whichever is shorter.
- •Major surgery ≤ 2 weeks prior to starting CC-
- •Pregnant or nursing females.
Arms & Interventions
Part A: CC-90002
CC-90002 will be given by intravenous (IV) infusion on a 28 day cycle
Intervention: CC-90002
Part B: CC-90002 with Rituximab
CC-90002 in combination with Rituximab will be given by intravenous (IV) infusion on a 28 day cycle in subjects with CD20-positive NHL
Intervention: CC-90002
Part B: CC-90002 with Rituximab
CC-90002 in combination with Rituximab will be given by intravenous (IV) infusion on a 28 day cycle in subjects with CD20-positive NHL
Intervention: Rituximab
Outcomes
Primary Outcomes
Dose-Limiting Toxicity (DLT)
Time Frame: Up to 18 months
Number of participants with a DLT
Maximum Tolerated Dose (MTD) - Part A
Time Frame: Up to 18 months
Dose that is the last dose level below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during Cycle 1.
Non-Tolerated Dose (NTD) - Part B
Time Frame: Up to 24 months
Dose at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in Cycle 1.
Maximum Tolerated Dose (MTD) - Part B
Time Frame: Up to 24 months
Dose that is the last dose level below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during Cycle 1.
Non-Tolerated Dose (NTD) - Part A
Time Frame: Up to 18 months
Dose at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in Cycle 1.
Secondary Outcomes
- Pharmacokinetics - AUC(Cycle 1 and beyond; and after discontinuation)
- Progression-free survival- Part B(Up to 2 years)
- Antitumor efficacy(Up to 36 months)
- Pharmacokinetics - tmax(Cycle 1 and beyond; and after discontinuation)
- Pharmacokinetics - T1/2(Cycle 1 and beyond; and after discontinuation)
- Pharmacokinetics - CL(Cycle 1 and beyond; and after discontinuation)
- Pharmacokinetics - Vmax(Cycle 1 and beyond; and after discontinuation)
- Overall Survival - Part B(Up to 2 years)
- Pharmacokinetics - Cmax(Cycle 1 and beyond; and after discontinuation)
- Anti-Drug Antibodies (ADAs)(Cycle 1 and beyond; and after discontinuation)