Safety and Efficacy Study of a Dual PI3K Delta/Gamma Inhibitor in Hematological Malignancies

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and efficacy of RP6530, a dual PI3K delta/gamma inhibitor in patients with hematologic malignancies.

Detailed Description
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The Maximum tolerated dose (MTD) will be determined based on the safety, pharmacokinetic (PK) and efficacy data. Safety analyses include AE's, AE's related to the drug, SAE's, laboratory values, vitals/ ECG and dose limiting toxicity (DLT). PK include measurement of peak plasma concentration (Cmax), area under the plasma concentration versus the time curve (AUC), time of maximum concentration observed (Tmax). Efficacy analyses include overall response rate (ORR) and duration of response (DOR).

Official Title
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A Phase I, Dose Escalation Study to Evaluate Safety and Efficacy of RP6530, a Dual PI3K Delta/Gamma Inhibitor, in Patients With Relapsed or Refractory Hematologic Malignancies

Conditions
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Lymphoma, B-Cell, T-Cell Lymphoma

Intervention / Treatment
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* Drug: RP6530


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory to or relapsed after at least 1 prior treatment line. ECOG performance status ≤2 Patients must be ≥18 years of age Able to give a written informed consent. Exclusion Criteria: Any cancer therapy in the last 4 weeks or limited palliative radiation <2 weeks Patients with HBV, HCV or HIV infection Autologous hematologic stem cell transplant within 3 months of study entry. Allogeneic hematologic stem cell transplant within 12 months. Previous therapy with GS-1101 (CAL-101, idelalisib), IPI-145, TGR-1202 or any drug that specifically inhibits PI3K/ mTOR (including temsirolimus, everolimus), AKT or BTK Inhibitor (including Ibrutinib). Patients on immunosuppressive therapy including systemic corticosteroids. Patients who are receiving chronic systemic anticoagulation therapy (warfarin sodium or heparin, etc.). Patients with known history of liver disorders. Patients with uncontrolled Diabetes Type I or Type II Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study. Women who are pregnant or lactating.

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: Single arm<br>RP6530 administered orally | Drug: RP6530<br>* Escalating doses starting at 25 mg BID<br>* Other names: PI3k Delta/ Gamma inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) and pharmacokinetics (PK) of RP6530 | To access maximum tolerated dose by clinical laboratory assessments, adverse events and dose limiting toxicities. PK parameter AUC, Cmax, tmax, t1/2 will be determined. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response following administration of RP6530 | Overall response rate (ORR) and duration of response (DOR). | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, SLL, NHL, SLL, PTCL, CTCL, MM, AML