A Safety and Preliminary Efficacy Study of CC-99282, Alone and in Combination With Anti-lymphoma Agents in Participants With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of CC-99282 alone and in combination with anti-lymphoma agents in participants with relapsed or refractory non-Hodgkin's lymphomas.

Detailed Description
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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.

Official Title
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A Phase 1/2, Multi-center, Open-label Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of an Orally Available Small Molecule, CC-99282, Alone and in Combination With Anti-Lymphoma Agents in Subjects With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL).

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: CC-99282
* Drug: Rituximab
* Drug: Obinutuzumab
* Drug: Tafasitamab
* Drug: Valemetostat


Participation Criteria
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Eligibility Criteria
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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

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Dose Escalation<br> | Drug: CC-99282<br>* Specified dose on specified days<br>* Other names: BMS-986369;|
| Experimental: Part B: Dose Expansion<br> | Drug: CC-99282<br>* Specified dose on specified days<br>* Other names: BMS-986369;Drug: Rituximab<br>* Specified dose on specified days<br>Drug: Obinutuzumab<br>* Specified dose on specified days<br>Drug: Tafasitamab<br>* Specified dose on specified days<br>Drug: Valemetostat<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) |  | From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) | 
| Number of participants with laboratory abnormalities |  | From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) | 
| Number of participants with vital sign abnormalities |  | From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) | 
| Number of participants with electrocardiogram (ECG) abnormalities |  | From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) | 
| Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities |  | From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) | 
| Number of participants with left ventricular ejection fraction (LVEF) assessment abnormalities |  | From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) | 
| Number of participants with physical examination abnormalities |  | From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) | 
| Dose Limiting Toxicity (DLT) |  | Up to 28 days in Cycle 1 | 
| Maximum tolerated dose (MTD) |  | Up to 28 days in cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics - Maximum plasma concentration of drug (Cmax) |  | Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) | 
| Pharmacokinetics - Area under the plasma concentration-time curve (AUC) |  | Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) | 
| Pharmacokinetics - Time to peak (maximum) plasma concentration (Tmax) |  | Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) | 
| Pharmacokinetics - Terminal-phase elimination half-life (T-HALF) |  | Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) | 
| Pharmacokinetics - Apparent total body clearance of the drug from the plasma (CLT/F) |  | Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) | 
| Pharmacokinetics: Apparent volume of distribution (Vz/F) |  | Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) | 
| Objective response rate (ORR) | 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 | Up to approximately 6 years | 
| Time to response (TTR) | Determined by the Lugano Classification for NHL response criteria | Up to approximately 6 years | 
| Duration of response (DoR) | Determined by the Lugano Classification for NHL response criteria | Up to approximately 6 years | 
| Progression free survival (PFS) | 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 | Up to approximately 6 years | 
| Overall survival (OS) | Time from first dose of CC-99282 to death from any cause Determined by the Lugano Classification for NHL response criteria | Up to approximately 6 years | 
| ORR | 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 | Up to approximately 4 years | 
| TTR | Determined using the modified International PCNSL Collaborative Group (IPCG) criteria | Up to approximately 4 years | 
| DOR | Determined using the modified International PCNSL Collaborative Group (IPCG) criteria | Up to approximately 4 years | 
| PFS | Determined using the modified International PCNSL Collaborative Group (IPCG) criteria | Up to approximately 4 years | 
| OS | Determined using the modified International PCNSL Collaborative Group (IPCG) criteria | Up to approximately 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkin Lymphomas (NHL), Safety, Efficacy, CC-99282, Rituximab, Relapsed, Refractory, Pharmacokinetics, Obinutuzumab, Tafasitamab, Valemetostat, Anti-lymphoma agents