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

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

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

Inclusion Criteria:

1. Age ≥18 years on the day of signing informed consent.

2. Histologically confirmed diagnosis of cHL.

3. 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

4. Must have ECOG performance status of 0 or 1

5. At least one bi-dimensional measurable lesion with minimum measurement of > 15 mm in the longest diameter.

6. Toxicities related to prior therapy must have returned to Grade 1 or less, except for alopecia.

   1. 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)
   2. Absolute neutrophil count (ANC) ≥1,000/µL
   3. Platelet count ≥75,000/μL
   4. Total bilirubin ≤1.5 times the ULN (or ≤3 x ULN, if patient has Gilbert syndrome)
   5. ALT and AST ≤2.5 x ULN
   6. Serum creatinine ≤ 1.5 x ULN or CrCl > 60 ml/min (Cockcroft-Gault formula)

7. Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential

8. Provide written informed consent prior to any study-specific screening procedures.

9. Willingness and capability to comply with the requirements of the study.

Exclusion Criteria:

1. 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,
2. 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)
3. Radiotherapy within the last 21 days prior to C1D1 (limited field palliative radiation is allowed if ≥ 14 days prior to C1D1);
4. Investigational drug therapy outside of this trial during or within 3 weeks prior to C1D1.
5. Patients with Allo-SCT on active GVHD or immunosuppression therapy within 3 months prior to C1D1.
6. Patient with active autoimmune disease or any medical condition requiring the use of systemic immunosuppressive medications .
7. Pregnancy or lactation.
8. Known clinically active CNS involvement.
9. Evidence of active Hepatitis B, active Hepatitis C infection (HCV) or cytomegalovirus (CMV) or known history of HIV.
10. Subjects with concomitant second malignancies
11. Patient with any active immune toxicity of Grade 1 or greater or any other severe or Grade 3 treatment-related adverse event.
12. History of Grade 4 anaphylactic reaction to monoclonal antibody therapy.