A Study of CC-95251, a Monoclonal Antibody Directed Against SIRPα, With Cetuximab in Subjects With Advanced Solid Cancers

Neoplasms Clinical Trial

Official title:

A Phase 1, Open-label, Dose Finding Study of CC-95251, a Monoclonal Antibody Directed Against SIRPα, Alone and in Combination With Cetuximab in Subjects With Advanced Solid Cancers

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03816254
• Other study ID #: CC-95251-ST-001
• Secondary ID: U1111-1224-8251
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: January 24, 2019
• Est. completion date: November 2, 2023

Study information

• Verified date: January 2019
• Source: Celgene
• Contact: Shailaja Uttamsingh
• Phone: 415-839-7053
• Email: suttamsingh[@]celgene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

Study CC-95251-ST-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), first-in-human clinical study of CC-95251 in subjects with advanced solid cancers. The dose escalation part (Part A) of the study will be conducted in two 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: November 2, 2023
• Est. primary completion date: April 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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 SIRPa.

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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• CC-95251
CC-95251 administered by IV (intravenous) infusion.
• Cetuximab
Cetuximab administered by IV (intravenous) infusion.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Event(s)	Number of subjects with adverse event	From enrollment until at least 56 days after completion of study treatment
Primary	Non-Tolerated Dose (NTD)	A dose that causes unacceptable side effects.	18 months
Primary	Maximum Tolerated Dose (MTD)	The highest dose that does not cause unacceptable side effects.	18 months
Primary	Dose-Limiting Toxicity (DLT)	Any adverse events meeting the protocol-defined DLT criteria.	30 months
Secondary	Overall response rate (ORR)	The percent of subjects whose best response is CR or PR.	42 Months
Secondary	Time to response (TTR)	Time from the first dose to the first objective tumor response observed for patients who achieved a CR or PR.	42 Months
Secondary	Duration of response (DOR)	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.	42 Months
Secondary	Progression free survival (PFS)	Time from the first dose to the first occurrence of disease progression or death from any cause.	42 Months
Secondary	Overall survival (OS)	Time from the first dose to death due to any cause.	42 Months
Secondary	Pharmacokinetic - Cmax	Maximum serum concentration of the drug	30 Months
Secondary	Pharmacokinetic - Cmin	Minimum serum concentration of the drug.	30 Months
Secondary	Pharmacokinetic - AUC	Area under the serum concentration time-curve of the drug.	30 Months
Secondary	Pharmacokinetic - tmax	Time to peak (maximum) serum concentration of the drug.	30 Months
Secondary	Pharmacokinetic - t1/2	Terminal half-life of the drug.	30 Months
Secondary	Pharmacokinetic - CL	Total body clearance of the drug from the serum.	30 Months
Secondary	Pharmacokinetic - Vss	Volume of distribution of the drug at steady state.	30 Months
Secondary	Anti-CC-95251 antibody (ADA) assessment	Determine the presence and frequency of anti-drug antibodies of the drug.	30 Months