A Study of CC-95251, a Monoclonal Antibody Directed Against SIRPα, in Subjects With Advanced Solid and Hematologic Cancers
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT03783403 Recruiting December 21, 2018 October 2, 2020

study description
Brief Summary

Study CC-95251-ST-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Parts B and C), first-in-human clinical study of CC-95251 in subjects with advanced cancers.

Condition or Disease: Neoplasms
Intervention/treatment: Drug: CC-95251
Drug: Rituximab
Drug: Cetuximab
Phase: Phase 1
Detailed Description

Study CC-95251-ST-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part
B & Part C), first-in-human clinical study of CC-95251 in subjects with advanced solid &
hematologic cancers. The dose escalation part (Part A) of the study will be conducted in
three stages. Stage 1 will evaluate the safety and tolerability of escalating doses of
CC-95251, administered IV, to determine the maximum tolerated dose (MTD), non-tolerated dose
(NTD), and/or recommended Phase 2 dose (RP2D) of CC-95251. Stage 2 will evaluate the safety
and tolerability of escalating doses of CC-95251 in combination with weekly cetuximab, both
administered IV, to determine the MTD, NTD, and/or RP2D of CC-95251 plus cetuximab. Stage 3
will evaluate the safety and tolerability of escalating doses of CC-95251 in combination with
rituximab, both administered IV, to establish MTD, NTD, and/or RP2D of CC-95251 plus
rituximab.


study design
Study Type: Interventional
Estimated Enrollment : 230 participants
Intervention Model : Single Group Assignment
Masking: None (Open Label) ()
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose Finding Study of CC-95251, A Monoclonal Antibody Directed Against SIRPa, Alone and in Combination With Cetuximab or Rituximab in Subjects With Advanced Solid and Hematologic Cancers
Actual Study Start Date: February 2019
Estimated Primary Completion Date: December 2022
Estimated Study Completion Date: December 2024

Arms and interventions
Arm Intervention/treatment
Experimental: CC-95251 alone
CC-95251 administered by IV (intravenous) infusion
Drug: CC-95251
CC-95251 administered by IV (intravenous) infusion.
Experimental: CC-95251 in combination with cetuximab
CC-95251 administered by IV (intravenous) infusion; Cetuximab administered by IV (intravenous) infusion.
Drug: CC-95251
CC-95251 administered by IV (intravenous) infusion.

Drug: Cetuximab
Cetuximab administered by IV (intravenous) infusion.
Experimental: CC-95251 in combination with rituximab
CC-95251 administered by IV (intravenous) infusion; Rituximab administered by IV (intravenous) infusion.
Drug: CC-95251
CC-95251 administered by IV (intravenous) infusion.

Drug: Rituximab
Rituximab administered by IV (intravenous) infusion.
outcome measures
Primary Outcome Measures: 1. Adverse Event(s) [ Time Frame: From enrollment until at least 56 days after completion of study treatment ]
Number of subjects with adverse event
2. Non-Tolerated Dose (NTD) [ Time Frame: 18 months ]
A dose that causes unacceptable side effects.
3. Maximum Tolerated Dose (MTD) [ Time Frame: 18 months ]
The highest dose that does not cause unacceptable side effects.
4. Dose-Limiting Toxicity (DLT) [ Time Frame: 30 months ]
Any adverse events meeting the protocol-defined DLT criteria.
Secondary Outcome Measures: 1. Overall response rate (ORR) [ Time Frame: 66 Months ]
The percent of subjects whose best response is CR or PR.
2. Time to response (TTR) [ Time Frame: 66 Months ]
Time from the first dose to the first objective tumor response observed for patients who achieved a CR or PR.
3. Duration of response (DOR) [ Time Frame: 66 Months ]
Time from the first objective tumor response observed for patients who achieved a CR or PR until the first date at progressive disease is objectively documented.
4. Progression free survival (PFS) [ Time Frame: 66 Months ]
Time from the first dose to the first occurrence of disease progression or death from any cause.
5. Overall survival (OS) [ Time Frame: 66 Months ]
Time from the first dose to death due to any cause.
6. Pharmacokinetic - Cmax [ Time Frame: 36 Months ]
Maximum serum concentration of the drug
7. Pharmacokinetic - Cmin [ Time Frame: 36 Months ]
Minimum serum concentration of the drug.
8. Pharmacokinetic - AUC [ Time Frame: 36 Months ]
Area under the serum concentration time-curve of the drug.
9. Pharmacokinetic - tmax [ Time Frame: 36 Months ]
Time to peak (maximum) serum concentration of the drug.
10. Pharmacokinetic - t1/2 [ Time Frame: 36 Months ]
Terminal half-life of the drug.
11. Pharmacokinetic - CL [ Time Frame: 36 Months ]
Total body clearance of the drug from the serum.
12. Pharmacokinetic - Vss [ Time Frame: 36 Months ]
Volume of distribution of the drug at steady state.
13. Anti-CC-95251 antibody (ADA) assessment [ Time Frame: 36 Months ]
Determine the presence and frequency of anti-drug antibodies of the drug.

Eligibility Criteria
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. Subject must understand and voluntarily sign an informed consent form (ICF).

2. Subject (male or female) is ≥ 18 years of age at the time of signing the ICF.

3. Subject must have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer therapy or for whom no other approved conventional therapy exists and have histological or cytological confirmation of advanced unresectable solid tumors.

4. Subject must have at least one site of measurable disease as determined by RECIST v1.1. NHL subjects must have bi-dimensionally measurable disease on cross sectional imaging by CT or MRI as defined by Lugano/IWG criteria.

5. Subject has an ECOG PS of 0 or 1.

6. Subjects must exhibit acceptable hematopoietic, liver, renal, and coagulation function as assessed by laboratory tests.

7. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

1. Subject has received prior investigational therapy directed at CD47 or SIRPα.

2. Subject has cancer with symptomatic central nervous system involvement.

3. Subject is on chronic systemic immunosuppressive therapy or corticosteroids.

4. Subjects with a history of clinically significant cardiac disease within the previous 6 months.

5. Subject had a prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting CC-95251, whichever is shorter.

6. Subject had major surgery ≤ 2 weeks prior to starting CC-95251.

7. Subject is a pregnant or lactating female.

8. Subject has known human immunodeficiency virus (HIV) infection.

9. Subject has known chronic, active hepatitis B or C (HBV/HCV) infection.

10. Ongoing treatment with chronic, therapeutic dosing of anti-coagulants.

11. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.

12. History of concurrent second cancers requiring active, ongoing systemic treatment.

13. For subjects receiving cetuximab, known history of cetuximab intolerance.


Contacts and Locations
Contacts

Contact:

Locations
United States, Alabama University of Alabama Birmingham Birmingham
United States, Arizona HonorHealth Research Institute Scottsdale
United States, California UC Davis Medical Center Sacramento
United States, Colorado Rocky Mountain Cancer Centers, LLP [Aurora-COAU] Aurora
United States, New York NYU Langone Laura and Isaac Perlmutter Cancer Center New York
United States, North Carolina Levine Cancer Institute Charlotte
United States, Oklahoma University of Oklahoma Peggy and Charles Stephenson Cancer Center Oklahoma City
United States, Oregon Providence Cancer Center/Earle A. Chiles Res. Inst. Portland
United States, Pennsylvania University of Pittsburgh Medical Center - Cancer Pavilion Pittsburgh
United States, Tennessee Tennessee Oncology Nashville
United States, Texas The University of Texas - MD Anderson Cancer Center Houston
United States, Texas US Oncology Research Irving
United States, Texas South Texas Accelerated Research Therapeutics San Antonio
United States, Texas Texas Oncology - San Antonio Medical Center San Antonio
Australia, New South Wales Chris O'Brien Lifehouse Camperdown
Australia, Victoria Austin Health - Austin Hospital Heidelberg
Australia, Victoria Peter MacCallum Cancer Centre Melbourne
Canada, Alberta Cross Cancer Institute Edmonton
Canada, Ontario Princess Margaret Cancer Centre Toronto
Sponsors and Collaborators
Celgene
Investigator
Study Director : Amar Patel, MD Celgene
More Information
Responsible Party : Celgene
ClinicalTrials.gov Identifier : NCT03783403     
Other Study ID Numbers : CC-95251-ST-001, U1111-1224-8251, NCT03816254
First Posted : December 21, 2018
Last Update Posted : October 2, 2020
Last Verified : September 2020
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene: Antibody
CC-95251
SIRPα
Advanced Solid Cancers
Advanced Hematologic Cancers
Additional relevant MeSH terms :
Hematologic Neoplasms