A Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hematologic Neoplasms

Intervention / Treatment
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* Drug: CC-90002
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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 1. 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-90002. 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-90002. Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-90002. 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-90002. Pregnant or nursing females. Known HIV infection. Known chronic, active hepatitis B or C (HBV/HCV) infection. Ongoing treatment with chronic, therapeutic dosing of anti-coagulants. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia. History of concurrent second cancers requiring active, ongoing systemic treatment. concurrent second cancers requiring active, ongoing systemic treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: CC-90002<br>CC-90002 will be given by intravenous (IV) infusion on a 28 day cycle | Drug: CC-90002<br> <br> |
| Experimental: Part B: CC-90002 with Rituximab<br>CC-90002 in combination with Rituximab will be given by intravenous (IV) infusion on a 28 day cycle in subjects with CD20-positive NHL | Drug: CC-90002<br> <br> Drug: Rituximab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting Toxicity (DLT) | Number of participants with a DLT | Up to 18 months | 
| Non-Tolerated Dose (NTD) - Part A | Dose at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in Cycle 1. | Up to 18 months | 
| Maximum Tolerated Dose (MTD) - Part A | 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. | Up to 18 months | 
| Non-Tolerated Dose (NTD) - Part B | Dose at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in Cycle 1. | Up to 24 months | 
| Maximum Tolerated Dose (MTD) - Part B | 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. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor efficacy | Determined by response rates of each tumor type using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and other tumor-appropriate response criteria. | Up to 36 months | 
| Pharmacokinetics - Cmax | Maximum observed concentration in serum | Cycle 1 and beyond; and after discontinuation | 
| Pharmacokinetics - AUC | Area under the serum concentration - time curve | Cycle 1 and beyond; and after discontinuation | 
| Pharmacokinetics - tmax | Time to peak (maximum) serum concentration | Cycle 1 and beyond; and after discontinuation | 
| Pharmacokinetics - T1/2 | Terminal half-life (T1/2) | Cycle 1 and beyond; and after discontinuation | 
| Pharmacokinetics - CL | Total body clearance of the drug from serum | Cycle 1 and beyond; and after discontinuation | 
| Pharmacokinetics - Vmax | Volume of distribution at steady-state | Cycle 1 and beyond; and after discontinuation | 
| Anti-Drug Antibodies (ADAs) | Determine the presence and frequency of anti-drug antibodies | Cycle 1 and beyond; and after discontinuation | 
| Overall Survival - Part B | Measured as the time from the first dose of CC-90002 to death due to any cause. | Up to 2 years | 
| Progression-free survival- Part B | Defined as the time from the first dose of CC-90002 to the first occurrence of disease progression or death from any cause | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-90002, Monoclonal, Antibody, CD47, Advanced, Solid Cancers, Hematologic Cancers