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

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

CC-90002-ST -001 is an open-label, Phase 1, dose escalation clinical study in subjects with advanced, refractory solid and hematologic cancers.

Study Overview

• Status: Completed
• Conditions: Hematologic Neoplasms
• Intervention / Treatment: Drug: Rituximab; Drug: CC-90002

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Badalona (Barcelona), Spain, 08916
    • Hospital Universitari Germans Trias i Pujol Can Ruti
  • Barcelona, Spain, 08035
    • Hospital Val d'Hebron
  • Barcelona, Spain, 08907
    • Duran i Reynals Institut Catala d'Oncologia
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Marques de Valdecilla
  • Valencia, Spain, 46009
    • Hospital de la Fe
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare Research Institute
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • San Francisco, California, United States, 94143-1270
      • University of California San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8073
      • Yale University School Of Medicine
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. At least one site of measurable disease in subjects with solid tumors and NHL.
3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
4. Subjects must have adequate hematopoietic, liver, renal and coagulation function as assessed by specific laboratory criteria.
5. 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:

1. High grade lymphomas (Burkitts or lymphoblastic), plasma cell leukemia.
2. High grade, rapidly proliferative solid tumors (eg, small cell lung cancer, germ cell tumors, neuroblastoma) with extensive tumor burden.
3. Symptomatic central nervous system involvement.
4. Impaired cardiac function or clinically significant cardiac disease.
5. Prior Red blood cell (RBC) transfusion < 3 months prior to starting CC-90002 (Part A only).
6. Prior autologous stem cell transplant ≤ 3 months prior to starting CC-90002.
7. Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-90002.
8. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks prior to starting CC-90002, whichever is shorter.
9. Major surgery ≤ 2 weeks prior to starting CC-90002.
10. Pregnant or nursing females.
11. Known HIV infection.
12. Known chronic, active hepatitis B or C (HBV/HCV) infection.
13. Ongoing treatment with chronic, therapeutic dosing of anti-coagulants.
14. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
15. History of concurrent second cancers requiring active, ongoing systemic treatment.

concurrent second cancers requiring active, ongoing systemic treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: CC-90002; CC-90002 will be given by intravenous (IV) infusion on a 28 day cycle	Drug: CC-90002
Experimental: 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	Drug: Rituximab; Drug: CC-90002

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Michael Burgess, MD, PhD, Celgene

Publications and helpful links

General Publications

• Narla RK, Modi H, Bauer D, Abbasian M, Leisten J, Piccotti JR, Kopytek S, Eckelman BP, Deveraux Q, Timmer J, Zhu D, Wong L, Escoubet L, Raymon HK, Hariharan K. Modulation of CD47-SIRPalpha innate immune checkpoint axis with Fc-function detuned anti-CD47 therapeutic antibody. Cancer Immunol Immunother. 2022 Feb;71(2):473-489. doi: 10.1007/s00262-021-03010-6. Epub 2021 Jul 10.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2015
• Primary Completion (Actual): December 24, 2020
• Study Completion (Actual): December 24, 2020

Study Registration Dates

• First Submitted: February 13, 2015
• First Submitted That Met QC Criteria: February 19, 2015
• First Posted (Estimate): February 20, 2015

Study Record Updates

• Last Update Posted (Actual): August 12, 2021
• Last Update Submitted That Met QC Criteria: August 10, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Antibody; Advanced; Hematologic Cancers; CD47; Monoclonal; Solid Cancers; CC-90002
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: CC-90002-ST-001; 2015-000101-39 (EudraCT Number)