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

Sponsor

Rhizen Pharmaceuticals SA (Industry)

Overall Status

Terminated

CT.gov ID

NCT03471351

Collaborator

(none)

Enrollment

Locations

Arm

6.9

Actual Duration (Months)

0.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Classical Hodgkin Lymphoma	Drug: Tenalisib Biological: Pembrolizumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 18, 2018

Actual Primary Completion Date :

Feb 13, 2019

Actual Study Completion Date :

Feb 13, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Maximum observed plasma concentration (Cmax) [21 days]
Assessment of Cmax in subjects treated with RP6530 and pembrolizumab combination
Overall response rate (ORR) with Tenalisib and Pembrolizumab combination [12 weeks]
No of patients with partial and complete response
Duration of Response (DoR) with Tenalisib and Pembrolizumab combination [12 weeks]
The time period from the response achieved in patient until the disease progression.
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
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
Provide written informed consent prior to any study-specific screening procedures.
Willingness and capability to comply with the requirements of the study.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637
2	Rhizen Pharmaceuticals investigational trial site; Karmanos Cancer Institute,	Detroit	Michigan	United States	48201
3	University of Washington	Seattle	Washington	United States	98109