Safety and Efficacy Study of a Dual PI3K Delta/Gamma Inhibitor in T-cell Lymphoma

Safety: Treatment-Emergent AE; Treatment-Related AE, SAE and Clinical significant AE; Dose Limiting Toxicities (DLT). PK: Peak Plasma Concentration (Cmax), Area under the plasma concentration versus time curve (AUC), Time of Maximum concentration observed (Tmax). Efficacy: Overall Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS) and Duration of Response.

• RP6530 (Drug), also known as PI3K inhibitor: Tablet starting at 200 mg

Primary outcomes

• Safety of RP6530 [28 days]: Number of participants with Treatment-Related Adverse Events as Assessed by CTACE v4.0

Secondary outcomes

• Overall Response Rate (ORR) With RP6530 [8 months]: ORR is defined as sum of CR and PR rates, Response assessment for PTCL based on IWG criteria (Cheson 2007) and CTCL on mSWAT/Global assessment (ISCL/EORTC guideline).
• Duration of Response (DOR) With RP6530 [24 months]: The time period from the response achieved in patient until the disease progression.
• Peak Plasma Concentration (Cmax) [Day 1 of Cycle 1]: Peak Plasma Concentration (Cmax) of RP6530

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Histologically confirmed T cell Non-Hodgkin Lymphoma (T-NHL)
* 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 3 weeks or limited palliative radiation <2 weeks
* Patients with HBV, HCV or HIV infection
* Previous therapy with GS-1101 (CAL-101, Idelalisib), IPI-145 (Duvelisib), TGR-1202 or any drug that specifically inhibits PI3K/ mTOR (including temsirolimus, everolimus), AKT or BTK Inhibitor (including Ibrutinib) in last 6 months
* Patients on immunosuppressive therapy including systemic corticosteroids.
* 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.

Participant flow

Outcome results

• Safety of RP6530 (Primary), Count of participants, Participants: Dose escalation_Cohort 1_200 mg 0; Dose escalation_Cohort 2_400 mg 0; Dose escalation_Cohort 3_800 mg (Fasting) 0; Dose escalation_Cohort 4_800 mg (Fed) 2; Dose expansion_PTCL_800 mg (Fasting) 0; Dose expansion_CTCL_800 mg (Fasting) 0
• Overall Response Rate (ORR) With RP6530 (Secondary), Count of participants, Participants: Dose escalation_Cohort 1_200 mg 1; Dose escalation_Cohort 2_400 mg 2; Dose escalation_Cohort 3_800 mg (Fasting) 2; Dose escalation_Cohort 4_800 mg (Fed) 2; Dose expansion_PTCL_800 mg (Fasting) 4; Dose expansion_CTCL_800 mg (Fasting) 5
• Duration of Response (DOR) With RP6530 (Secondary), Median, Days: Dose escalation_Cohort 1_200 mg 147 (147 to 147); Dose escalation_Cohort 2_400 mg 72 (29 to 115); Dose escalation_Cohort 3_800 mg (Fasting) 313 (68 to 557); Dose escalation_Cohort 4_800 mg (Fed) 99 (50 to 148); Dose expansion_PTCL_800 mg (Fasting) 141 (56 to 391); Dose expansion_CTCL_800 mg (Fasting) 307 (67 to 588)
• Peak Plasma Concentration (Cmax) (Secondary), Mean, ng/mL: Dose escalation_Cohort 1_200 mg 1297.65 +/- 622.81; Dose escalation_Cohort 2_400 mg 2196.65 +/- 676.45; Dose escalation_Cohort 3_800 mg (Fasting) 3995.68 +/- 1392.74; Dose escalation_Cohort 4_800 mg (Fed) 2668.05 +/- 1713.17

Adverse events

Time frame: 24 months

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2018-05-23)
• Statistical Analysis Plan (PDF, 2018-05-23)

• Auris Huen, MD, Principal investigator, MD Anderson Cancer Center, Houston, Tx.