Detailed Description:
Participants with relapsed or refractory non-Hodgkin's lymphomas (R/R NHL) who have failed at
least 2 lines of therapy (or have received at least one prior line of standard therapy and
are not eligible for any other therapy).
The dose escalation will evaluate the safety and tolerability of escalating doses of CC-99282
in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) and/or relapsed or
refractory follicular lymphoma (R/R FL) participants to determine the maximum tolerated dose
(MTD) of CC-99282 as monotherapy.
The dose expansion will further evaluate the safety and preliminary efficacy of single agent
CC-99282 or the safety and preliminary efficacy of CC-99282 in combination with anti-lymphoma
agents in participants with R/R DLBCL and NHL.
Part B Cohort B will further evaluate the potential effects of food on the PK and safety of
CC-99282.
Inclusion Criteria:
- History of Non-Hodgkin's Lymphoma (NHL) with relapsed or refractory disease
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion Criteria:
- Life expectancy ≤ 2 months
- Received prior systemic anti-cancer treatment (approved or investigational) ≤ 5
half-lives or 4 weeks prior to starting CC-99282, whichever is shorter
- Is on chronic systemic immunosuppressive therapy or corticosteroids or has clinically
significant graft-versus-host disease (GVHD)
- Impaired cardiac function or clinically significant cardiac disease
Other protocol-defined inclusion/exclusion criteria apply
Primary outcome:
1. Incidence of Adverse Events (AEs) (Time Frame - From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years))
2. Number of participants with laboratory abnormalities (Time Frame - From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years))
3. Number of participants with vital sign abnormalities (Time Frame - From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years))
4. Number of participants with electrocardiogram (ECG) abnormalities (Time Frame - From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years))
5. Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities (Time Frame - From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years))
6. Number of participants with left ventricular ejection fraction (LVEF) assessment abnormalities (Time Frame - From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years))
7. Number of participants with physical examination abnormalities (Time Frame - From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years))
8. Dose Limiting Toxicity (DLT) (Time Frame - Up to 28 days in Cycle 1)
9. Maximum tolerated dose (MTD) (Time Frame - Up to 28 days in cycle 1)
Secondary outcome:
1. Pharmacokinetics - Maximum plasma concentration of drug (Cmax) (Time Frame - Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
2. Pharmacokinetics - Area under the plasma concentration-time curve (AUC) (Time Frame - Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
3. Pharmacokinetics - Time to peak (maximum) plasma concentration (Tmax) (Time Frame - Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
4. Pharmacokinetics - Terminal-phase elimination half-life (T-HALF) (Time Frame - Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
5. Pharmacokinetics - Apparent total body clearance of the drug from the plasma (CLT/F) (Time Frame - Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
6. Pharmacokinetics: Apparent volume of distribution (Vz/F) (Time Frame - Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
7. Objective response rate (ORR) (Time Frame - Up to approximately 6 years):
Defined as the percent of subjects whose best response is Complete Response (CR) or Partial Response (PR).
Determined by the Lugano Classification for NHL response criteria
8. Time to response (TTR) (Time Frame - Up to approximately 6 years):
Determined by the Lugano Classification for NHL response criteria
9. Duration of response (DoR) (Time Frame - Up to approximately 6 years):
Determined by the Lugano Classification for NHL response criteria
10. Progression free survival (PFS) (Time Frame - Up to approximately 6 years):
Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause
Determined by the Lugano Classification for NHL response criteria
11. Overall survival (OS) (Time Frame - Up to approximately 6 years):
Time from first dose of CC-99282 to death from any cause
Determined by the Lugano Classification for NHL response criteria
12. ORR (Time Frame - Up to approximately 4 years):
Defined as the percent of subjects whose best response is Complete Response (CR) or Partial Response (PR).
Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
13. TTR (Time Frame - Up to approximately 4 years):
Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
14. DOR (Time Frame - Up to approximately 4 years):
Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
15. PFS (Time Frame - Up to approximately 4 years):
Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
16. OS (Time Frame - Up to approximately 4 years):
Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
- Experimental: Part A: Dose Escalation
- Experimental: Part B: Dose Expansion
- CC-99282 (BMS-986369):
Specified dose on specified days - Rituximab:
Specified dose on specified days - Obinutuzumab:
Specified dose on specified days - Tafasitamab:
Specified dose on specified days - Valemetostat:
Specified dose on specified days
Quelle: ClinicalTrials.gov
