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.

Study Overview

• Status: Terminated
• Conditions: Classical Hodgkin Lymphoma
• Intervention / Treatment: Drug: Tenalisib; Biological: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Rhizen Pharmaceuticals investigational trial site; Karmanos Cancer Institute,
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rhizen Pharmaceuticals SA

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2018
• Primary Completion (Actual): February 13, 2019
• Study Completion (Actual): February 13, 2019

Study Registration Dates

• First Submitted: February 15, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 20, 2018

Study Record Updates

• Last Update Posted (Actual): December 27, 2019
• Last Update Submitted That Met QC Criteria: December 24, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Pembrolizumab; Hodgkin lymphoma; Tenalisib; RP6530
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Phosphoinositide-3 Kinase Inhibitors; Pembrolizumab; Tenalisib
• Other Study ID Numbers: RP6530+Pembrolizumab-1701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No