INCB040093 and INCB040093 Combined With Itacitinib (INCB039110) in Relapsed/Refractory Hodgkin Lymphoma

Study Overview
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Brief Summary
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A Phase 2, open-label study to evaluate the safety and efficacy of INCB040093 as monotherapy and as combination therapy with itacitinib (INCB039110) in subjects with relapsed or refractory Hodgkin Lymphoma.

Official Title
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A Phase 2, Open-Label Study of the Safety and Efficacy of INCB40093 and INCB40093 Combined With Itacitinib (INCB039110) in Subjects With Relapsed or Refractory Hodgkin Lymphoma

Conditions
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Refractory Hodgkin Lymphoma, Recurrent Adult Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: INCB040093 Monotherapy
* Drug: INCB040093
* Drug: itacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, aged 18 years or older Histologically confirmed diagnosis of classical HL Must be relapsed or refractory after autologous stem cell transplant (ASCT) and/or 2 or more prior chemotherapy regimens Must have had prior treatment with brentuximab vedotin or not a candidate for treatment with brentuximab vedotin Eastern Cooperative Oncology Group (ECOG) 0 to 2 Exclusion Criteria: Laboratory parameters not within the protocol-defined range Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study drug. Received any approved anticancer medications within 21 days or 5 half-lives (whichever is longer) prior to receiving their first dose of study drug EXCEPT steroids at ≤ 10 mg prednisone daily (or equivalent). Has any unresolved toxicity ≥ Grade 2 from previous anticancer therapy Received autologous stem cell transplant within 28 days or allogeneic transplant within 3 months prior to first dose of study drug History of lymphoma involving the central nervous system Evidence of active or prior hepatitis infection.

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INCB040093 Monotherapy<br>INCB040093 sustained release (SR) tablets will be administered orally twice daily (BID) without regard to food. | Drug: INCB040093 Monotherapy<br>* INCB040093 sustained release (SR) tablets will be administered orally twice daily (BID) without regard to food.<br>|
| Experimental: INCB040093 and itacitinib (INCB039110) Combination Therapy<br>Subjects allocated to Group B will be given INCB040093 BID in combination with itacitinib SR tablets. The dose of itacitinib will be orally given once daily (QD). Doses should be taken in the morning on an empty stomach if possible. | Drug: INCB040093<br>* INCB040093 sustained release (SR) tablets will be administered orally twice daily (BID) without regard to food.<br>Drug: itacitinib<br>* The dose of itacitinib will be given orally once daily (QD).<br>* Other names: INCB039110;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) as determined by the percentage of subjects achieving a partial response (PR) or complete response (CR) | Evaluate the efficacy of INCB040093 as monotherapy and when given in combination with itacitinib by assessing the objective response rate (ORR) determined by an independent review committee. | Measured every 9 weeks from baseline until progression (estimated to be 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants reporting adverse events in the monotherapy group | Safety and tolerability of INCB040093 as monotherapy in subjects with relapsed or refractory Hodgkin's lymphoma (HL) as determined by clinical laboratory assessments, physical exams, 12-lead ECG and summary of adverse events | every 3 weeks for the duration of participation in the study [estimated to be 12 months] | 
| Percentage of participants reporting adverse events in the combination therapy group | Safety and tolerability of INCB040093 when given in combination with itacitinib in subjects with relapsed or refractory Hodgkin's lymphoma (HL) as determined by clinical laboratory assessments, physical exams, 12-lead ECG and summary of adverse events | every 3 weeks for the duration of participation in the study [estimated to be 12 months] | 
| Percentage of subjects achieving a complete response (CR) determined by the independent review committee and based on standard response criteria | Complete Response is determined by the independent review committee and based on standard response criteria defined by the Response Evaluation Criteria in Solid Tumor (RECIST) criteria. CR: Disappearance of all target and nontarget lesions. | Week 36 disease evaluation | 
| To evaluate the duration of response (DOR) | Duration of response is defined as the time from the first assessment showing response (CR or PR) determined by the independent review committee to the first documented disease progression determined by the independent review committee or death due to any cause, whichever occurs first. | Week 36 disease evaluation | 
| To evaluate the progression-free survival (PFS) | PFS was defined as the time from first dose to the first documented disease progression or relapse as assessed by independent review committee or death from any cause. | Week 36 disease evaluation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory Hodgkin lymphoma, Relapsed Hodgkin Lymphoma