NAVAL-1: An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas

Sponsor

Viracta Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05011058

Collaborator

(none)

140

Enrollment

Locations

Arm

78.1

Anticipated Duration (Months)

2.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive lymphomas

Condition or Disease	Intervention/Treatment	Phase
Epstein-Barr Virus Associated Lymphoproliferative Disorder EBV-Related PTLD EBV Related Non-Hodgkin's Lymphoma Extranodal NK/T-cell Lymphoma EBV-Positive DLBCL, Nos EBV Associated Lymphoma EBV-Related Hodgkin Lymphoma EBV Related PTCL, Nos	Drug: Nanatinostat in combination with valganciclovir	Phase 2

Detailed Description

Patients with EBV-associated lymphomas have inferior outcomes with standard-of-care therapies compared to those with EBV-negative disease. Nanatinostat is a selective class I HDAC inhibitor which induces EBV lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form. This open-label, multicenter, multinational, single-arm, Phase 2 basket study employs a Simon's 2-stage design to allow termination of enrollment into cohorts where treatment appears futile, and will include the following cohorts of patients with EBV+ relapsed/refractory lymphomas:

EBV+ diffuse large B-cell lymphoma (DLBCL, NOS)
Extranodal NK/T-cell lymphoma (ENKTL)
Peripheral T-cell lymphoma (PTCL), including PTCL-NOS and AITL
Hodgkin lymphoma (HL)
Post-transplant lymphoproliferative disorder (PTLD)
HIV-associated lymphomas (Plasmablastic, Burkitt, Hodgkin, DLBCL)
EBV+ lymphoproliferative disorders other than the above

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is an open-label, single-arm study utilizing a basket trial design.This is an open-label, single-arm study utilizing a basket trial design.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas

Actual Study Start Date :

May 28, 2021

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nanatinostat with Valganciclovir Patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week with valganciclovir 900 mg orally once daily. Up to 10 PTCL patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week.	Drug: Nanatinostat in combination with valganciclovir Drug: Nanatinostat, 20 mg orally once daily, 4 days per week in 28 day cycles Other name: VRx-3996 Drug: Valganciclovir, 900 mg orally once daily in 28 day cycles

Arm

Intervention/Treatment

Experimental: Nanatinostat with Valganciclovir

Patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week with valganciclovir 900 mg orally once daily. Up to 10 PTCL patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week.

Drug: Nanatinostat in combination with valganciclovir

Drug: Nanatinostat, 20 mg orally once daily, 4 days per week in 28 day cycles Other name: VRx-3996 Drug: Valganciclovir, 900 mg orally once daily in 28 day cycles

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [Approximately 3 years]
Assessed by an Independent Review Committee (IRC) per the 2007 International Working Group Response Criteria (IWGRC)

Secondary Outcome Measures

Duration of response (DOR) [Approximately 3 years]
Time to next anti-lymphoma treatment (TTNLT) [Approximately 3 years]
Progression-free survival (PFS) [Approximately 3 years]
Time to progression (TTP) [Approximately 3 years]
Overall survival [Approximately 3 years]
Incidence and severity of treatment-emergent adverse events [Approximately 28 days following the last dose]
Pharmacokinetic parameter - time to maximum plasma concentration [tmax], [Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)]
Pharmacokinetic parameter - maximum plasma concentration [Cmax] [Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)]
Pharmacokinetic parameter - area under the plasma concentration-time curve [AUC] [Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

EBV+ relapsed/refractory lymphoma following 2 or more prior systemic therapies
EBV+ DLBCL, NOS: Must have received at least one course of an anti-CD20 immunotherapy, and at least one course of anthracycline-based chemotherapy
PTLD: Must have received immunotherapy with an anti-CD20 agent.
Hodgkin lymphoma: Must have received at least one course of anthracycline-based chemotherapy. Patients with classical Hodgkin lymphoma should have failed or be ineligible for an anti-PD-1 agent and CD30-directed therapy.
For ENKTL and PTCL patients only: Relapsed/refractory disease following 1 or more prior systemic therapies. ENKTL patients must have failed an asparaginase-containing regimen.
No available therapies in the opinion of the Investigator
Not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or CAR-T therapy
Measurable disease per Lugano 2007
ECOG performance status 0, 1, 2
Adequate bone marrow function

Key Exclusion Criteria:

Presence or history of CNS involvement by lymphoma
Systemic anticancer therapy or CAR-T within 21 days
Antibody (anticancer) agents within 28 days
Less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant
Less than 90 days from prior allogeneic transplant.
Daily corticosteroids (≥20 mg of prednisone or equivalent) within week prior to Cycle 1 Day 1
Inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir.
Active infection requiring systemic therapy (excluding viral upper respiratory tract infections).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35233
2	University of Arizona Cancer Center	Tucson	Arizona	United States	85719
3	University of California Irvine	Orange	California	United States	92868
4	Scripps MD Anderson Cancer Center	San Diego	California	United States	92103
5	UCSF Hematology and Blood and Marrow Transplant	San Francisco	California	United States	94143
6	The Oncology Institute of Hope and Innovation	Torrance	California	United States	90503
7	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
8	Mid Florida Hematology and Oncology Center	Orange City	Florida	United States	32763
9	Norton Cancer Institute	Louisville	Kentucky	United States	40241
10	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
11	St. Vincent Healthcare Cancer Center	Billings	Montana	United States	59102
12	Roswell Park Comprehensive Cancer Center	Buffalo	New York	United States	14203
13	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
14	Sidney Kimmel Cancer Center - Jefferson Health	Philadelphia	Pennsylvania	United States	19107
15	Medical University of South Carolina	Charleston	South Carolina	United States	29425
16	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
17	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
18	Cross Cancer Institute	Edmonton	Alberta	Canada
19	Princess Margaret Cancer Centre	Toronto	Ontario	Canada
20	Hôpital Maisonneuve-Rosemont	Montréal	Quebec	Canada
21	Institut Bergonié	Bordeaux Cedex	Aquitaine	France
22	Hôpital Universitaire Pitié Salpêtrière	Paris	Ile-de-France	France
23	Centre Hospitalier Universitaire Limoges	Limoges cedex	Limousin	France
24	Hôpital Haut-Lévêque	Pessac	Nouvelle-Aquitaine	France
25	Centre Hospitalier Départemental Vendée	La Roche-sur-Yon	Pays De La Loire	France
26	Hôpital Saint-Eloi	Montpellier Cedex 5	Provence Alpes Cote d'Azur	France
27	Centre Hospitalier Lyon-Sud	Pierre-Bénite	Rhone-Alps	France
28	Universitätsklinikum Würzburg	Würzburg	Bavaria	Germany
29	Klinikum Oldenburg	Oldenburg	Niedersachsen	Germany
30	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen	Germany
31	Klinikum Chemnitz	Chemnitz	Saxony	Germany
32	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia	Italy
33	Istituto Clinico Humanitas	Rozzano	Milan	Italy
34	Centro di Riferimento Oncologico	Aviano	Pordenone	Italy
35	Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi	Bologna		Italy
36	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia		Italy
37	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano		Italy
38	Istituto Europeo di Oncologia	Milano		Italy
39	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy
40	Arcispedale Santa Maria Nuova	Reggio Emilia		Italy
41	Keimyung University Dongsan Hospital	Daegu	Gyeongsangbugdo	Korea, Republic of
42	Inje University Busan Paik Hospital	Busan		Korea, Republic of
43	Kyungpook National University Hospital	Daegu		Korea, Republic of
44	Gachon University Gil Medical Center	Incheon		Korea, Republic of
45	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of
46	National Cancer Centre Singapore	Singapore		Singapore
47	Oncocare Cancer Center	Singapore		Singapore
48	Singapore General Hospital	Singapore		Singapore
49	Taipei Veterans General Hospital	Taipei City	Taipei	Taiwan
50	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan
51	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan
52	China Medical University Hospital	Taichung City		Taiwan
53	National Cheng Kung University Hospital	Tainan		Taiwan
54	National Taiwan University Hospital	Taipei City		Taiwan
55	Chang Gung Memorial Hospital - Linkou Branch	Taoyuan		Taiwan
56	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool		United Kingdom
57	University College London Hospitals NHS Foundation Trust	London		United Kingdom
58	The Christie NHS Foundation Trust	Manchester		United Kingdom