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

Phase 1

Terminated

• Conditions: Classical Hodgkin Lymphoma
• Interventions: Drug: Tenalisib; Biological: Pembrolizumab

• Registration Number: NCT03471351
• Lead Sponsor: Rhizen Pharmaceuticals SA

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-15
• Study First Submitted QC: 2018-03-13
• Study First Posted: 2018-03-20
• Study Start: 2018-07-18
• Primary Completion: 2019-02-13
• Study Completion: 2019-02-13
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-24
• Last Update Posted: 2019-12-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tenalisib+Pembrolizumab	Pembrolizumab	Participants receive Tenalisib in escalating doses Orally BID and pembrolizumab as a fixed dose intravenously (IV) in Escalation and Expansion.
Tenalisib+Pembrolizumab	Tenalisib	Participants receive Tenalisib in escalating doses Orally BID and pembrolizumab as a fixed dose intravenously (IV) in Escalation and Expansion.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) for Tenalisib in combination with Pembrolizumab in patients with cHL	21 days	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.

Secondary Outcome Measures

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

Trial Locations

Locations (3)

University of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Rhizen Pharmaceuticals investigational trial site; Karmanos Cancer Institute,; 🇺🇸 Detroit, Michigan, United States