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

NCT03471351 | Terminated Phase 1 FDA Drug

• 1 other identifier: RP6530+Pembrolizumab-1701
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Classical Hodgkin Lymphoma

Keywords

Hodgkin lymphoma; RP6530; Pembrolizumab; Tenalisib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Maximum observed plasma concentration (Cmax)

  21 days

• Overall response rate (ORR) with Tenalisib and Pembrolizumab combination

  12 weeks

• Duration of Response (DoR) with Tenalisib and Pembrolizumab combination

  12 weeks

• Progression free survival (PFS) with Tenalisib and Pembrolizumab combination

  12 weeks

• Conversion Rate with Tenalisib and Pembrolizumab combination

  12 weeks

Study Arms (1)

Tenalisib+Pembrolizumab

EXPERIMENTAL

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

Drug: Tenalisib; Biological: Pembrolizumab

Interventions

Tenalisib DRUG

Tenalisib, BID, orally and Pembrolizumab 200 mg IV Q3W

Also known as: RP6530

Tenalisib+Pembrolizumab

Pembrolizumab BIOLOGICAL

Tenalisib, BID, orally and Pembrolizumab 200 mg IV Q3W

Tenalisib+Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years on the day of signing informed consent.
• Histologically confirmed diagnosis of cHL.
• 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
• Must have ECOG performance status of 0 or 1
• At least one bi-dimensional measurable lesion with minimum measurement of \> 15 mm in the longest diameter.
• Toxicities related to prior therapy must have returned to Grade 1 or less, except for alopecia.
• 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)
• Absolute neutrophil count (ANC) ≥1,000/µL
• Platelet count ≥75,000/μL
• Total bilirubin ≤1.5 times the ULN (or ≤3 x ULN, if patient has Gilbert syndrome)
• ALT and AST ≤2.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or CrCl \> 60 ml/min (Cockcroft-Gault formula)
• Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential

You may not qualify if:

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

Sponsors & Collaborators

• Rhizen Pharmaceuticals SA: lead

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Rhizen Pharmaceuticals investigational trial site; Karmanos Cancer Institute,

Detroit, Michigan, 48201, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

tenalisib; pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2018
• First Posted: March 20, 2018
• Study Start: July 18, 2018
• Primary Completion: February 13, 2019
• Study Completion: February 13, 2019
• Last Updated: December 27, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)