Safety and Efficacy Study of Tenalisib (RP6530) in Combination With Pembrolizumab in Relapsed or Refractory cHL

Study Overview
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Brief Summary
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To characterize safety, tolerability and to establish the maximum tolerated dose (MTD) for Tenalisib in combination with Pembrolizumab in patients with cHL.

Official Title
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An Open Label, Phase I/II Study to Evaluate the Safety and Efficacy of RP6530, a Novel PI3K δ/γ Dual Inhibitor Given in Combination With an Anti-PD-1 Therapy, Pembrolizumab in Adult Patients With Relapsed or Refractory cHL

Conditions
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Classical Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Tenalisib
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years on the day of signing informed consent. Histologically confirmed diagnosis of cHL. Disease status as defined as. Refractory patients who are naïve to anti-PD-1/PDL-1 therapy OR Relapsed after 3 or more lines of therapies; and are naïve to anti-PD-1/PDL-1 therapy OR Patients currently on Pembrolizumab and achieve a less than complete response Must have ECOG performance status of 0 or 1 At least one bi-dimensional measurable lesion with minimum measurement of > 15 mm in the longest diameter. Toxicities related to prior therapy must have returned to Grade 1 or less, except for alopecia. Adequate bone marrows, liver and renal function as assessed by the following laboratory requirements. Hemoglobin ≥8.0 g/dL (may not be transfused or treated with erythropoietin in preceding week to maintain or exceed this level) Absolute neutrophil count (ANC) ≥1,000/µL Platelet count ≥75,000/μL Total bilirubin ≤1.5 times the ULN (or ≤3 x ULN, if patient has Gilbert syndrome) ALT and AST ≤2.5 x ULN Serum creatinine ≤ 1.5 x ULN or CrCl > 60 ml/min (Cockcroft-Gault formula) Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential Provide written informed consent prior to any study-specific screening procedures. Willingness and capability to comply with the requirements of the study. Exclusion Criteria: Patient receiving anticancer therapy (e.g. chemotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization) ≤3 weeks or 5 half-lives (whichever is shorter) prior to C1D1, Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) Radiotherapy within the last 21 days prior to C1D1 (limited field palliative radiation is allowed if ≥ 14 days prior to C1D1); Investigational drug therapy outside of this trial during or within 3 weeks prior to C1D1. Patients with Allo-SCT on active GVHD or immunosuppression therapy within 3 months prior to C1D1. Patient with active autoimmune disease or any medical condition requiring the use of systemic immunosuppressive medications . Pregnancy or lactation. Known clinically active CNS involvement. Evidence of active Hepatitis B, active Hepatitis C infection (HCV) or cytomegalovirus (CMV) or known history of HIV. Subjects with concomitant second malignancies Patient with any active immune toxicity of Grade 1 or greater or any other severe or Grade 3 treatment-related adverse event. History of Grade 4 anaphylactic reaction to monoclonal antibody therapy.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenalisib+Pembrolizumab<br>Participants receive Tenalisib in escalating doses Orally BID and pembrolizumab as a fixed dose intravenously (IV) in Escalation and Expansion. | Drug: Tenalisib<br>* Tenalisib, BID, orally and Pembrolizumab 200 mg IV Q3W<br>* Other names: RP6530;Biological: Pembrolizumab<br>* Tenalisib, BID, orally and Pembrolizumab 200 mg IV Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) for Tenalisib in combination with Pembrolizumab in patients with cHL | The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle of treatment. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) | Assessment of Cmax in subjects treated with RP6530 and pembrolizumab combination | 21 days | 
| Overall response rate (ORR) with Tenalisib and Pembrolizumab combination | No of patients with partial and complete response | 12 weeks | 
| Duration of Response (DoR) with Tenalisib and Pembrolizumab combination | The time period from the response achieved in patient until the disease progression. | 12 weeks | 
| Progression free survival (PFS) with Tenalisib and Pembrolizumab combination | Progression-free survival was defined as the time from enrollment in the study to disease progression | 12 weeks | 
| Conversion Rate with Tenalisib and Pembrolizumab combination | Defined as improved outcome status (i.e Improve from PR to CR or from SD to PR) | 12 weeks | 
| Proportion of patients achieving CR and PR with Tenalisib and Pembrolizumab combination |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RP6530, Hodgkin lymphoma, Pembrolizumab, Tenalisib