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

Classical Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03471351
• Other study ID #: RP6530+Pembrolizumab-1701
• Status: Terminated
• Phase: Phase 1
• Start date: July 18, 2018
• Est. completion date: February 13, 2019

Study information

• Verified date: December 2019
• Source: Rhizen Pharmaceuticals SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 13, 2019
• Est. primary completion date: February 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Classical Hodgkin Lymphoma
• Hodgkin Disease

Intervention

Drug:
• Tenalisib
Tenalisib, BID, orally and Pembrolizumab 200 mg IV Q3W

Biological:
• Pembrolizumab
Tenalisib, BID, orally and Pembrolizumab 200 mg IV Q3W

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	Rhizen Pharmaceuticals investigational trial site; Karmanos Cancer Institute,	Detroit	Michigan
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Rhizen Pharmaceuticals SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Maximum observed plasma concentration (Cmax)	Assessment of Cmax in subjects treated with RP6530 and pembrolizumab combination	21 days
Secondary	Overall response rate (ORR) with Tenalisib and Pembrolizumab combination	No of patients with partial and complete response	12 weeks
Secondary	Duration of Response (DoR) with Tenalisib and Pembrolizumab combination	The time period from the response achieved in patient until the disease progression.	12 weeks
Secondary	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
Secondary	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
Secondary	Proportion of patients achieving CR and PR with Tenalisib and Pembrolizumab combination		12 weeks