VIRACTA THERAPEUTICS, INC. A Global Phase 2 Trial of Nanatinostat in Combination with Valganciclovir in Patients with EBV-Positive (EBV+) Relapsed/Refractory Peripheral T-Cell Lymphomas (NAVAL-1)
Hung Chang, MD, Hui-Hua Hsiao, MD, PhD, Tsai-Yun Chen, MD, Hung-Lin Liu, MD, Shih-Peng Yeh, MD, Ting-An Lin, MD, Yu-Cheng Chang, MD, Donald Strickland, MD, and Ming Yao, MD
Epstein-Barr Virus (EBV): A High Global Cancer Priority
EBV+ malignancies account for ~2% of new cancer cases globally and associated with adverse survival outcomes
- ~90% of the adult population are infected w/ EBV
- Persists as a life-long latent infection, remaining dormant within cell nuclei
- Latency confers resistance to anti-viral therapies and facilitates evasion of immune detection
- Linked to a variety of cancers
- >300,000 new cases/year of EBV+ lymphomas and solid tumors2
- Poor prognosis
- Responsible for ~180,000 cancer deaths/year2
Peripheral T-Cell Lymphoma1
(Overall Survival)
1Haverkos BM et al. Int J Cancer. 2017; 140:1899-1906; Dupuis J et al. Blood. 2006;108:4163-92 Wu L, et al. Exp. Therapeutic Med. 15: 3687, 2018; Kahn G, et al. BMJ 10:1136, 2020. | 2 |
Lymphoma Cell with Latent EBV
The "Kick and Kill" approach for EBV- associated lymphomas
Sensitizing EBV+
tumors to the
cytotoxic effects of ganciclovir (GCV)
Haverkos et al, Blood Adv 2023. 7 (20): 6339-6350 | 3 |
Study VT3996-201 (Phase 1b/2 Open Label Study) Showed Encouraging Anti-Tumor Activity in Relapsed/Refractory EBV+ Lymphoma1
- 55 patients enrolled across multiple EBV+ lymphoma subtypes
- 13 with nodal PTCL (8 AITL, 5 PTCL-NOS)
- 8 PTCL patients evaluable for efficacy2
- Eligibility:
- R/R EBV lymphoma (by local pathology), any histology
-
≥1 prior therapies with no curative options per
Investigator - ECOG PS: 0-2
Study VT3996-201 | |
R/R EBV+ PTCL Data1 | |
(n=13) | |
Evaluable Patients3 | |
(n=8) | |
Response | |
ORR | 4 (50%) |
CR | 3 (38%) |
PR | 1 |
SD | 1 |
PD | 3 |
Clinical Benefit Rate | 5 (63%) | |||
DOR | 17.3 months | |||
CR=complete response; PR=partial response; SD=stable disease; PD=progressive disease; ORR=overall response rate | ||||
1Haverkos et al, Blood Adv 2023; 7 (20): 6339-6350;2Pereira et al, Hematol Transfus Cell Ther 2023; 45 (2) S344-S345,2Data presented at HEMO 2023, | 3Evaluable patients: EBER- | 4 | ||
ISH+ with ≥1 post-treatment response assessment | ||||
NAVAL-1 Trial Design: Pivotal Phase 2 Study in Patients with R/R EBV+ Lymphoma
Global study with an adaptive Simon 2-stage design
Patient population:
- R/R EBV+ lymphoma with ≥1 prior therapies and no curative options
PTCL cohort randomization:
• Patients randomized to either |
Stage 1 (n=10) | Stage 2 (n=11) |
(Stage 1 + Stage 2 = 21) | |
EBV+ PTCL
- Combination Nstat + VGCV therapy arm completed enrollment of Stages 1 and 2
Potential Stage 2
Expansion
combination Nstat + VGCV therapy |
or Nstat monotherapy in Stage 1 |
Primary endpoint:
- Objective response rate (ORR) by independent central review
- Potential to further expand indications with promising anti- tumor activity after Stage 2
EBV+ PTCL
- Nstat monotherapy arm closed after 10 patients
EBV+ DLBCL
EBV+ PTLD
Expand lymphoma subtype(s) from Stage 1 meeting ORR threshold of 2/10 responses
Further expansion of promising lymphoma subtype(s) with additional patients may support registration
Other
R/R: Relapsed or Refractory, PTCL: Peripheral T-cell lymphoma, DLBCL: Diffuse large B-cell lymphoma (DLBCL), PTLD: Post-transplant lymphoproliferative | 5 |
NAVAL-1 R/R EBV+ PTCL Arm Study Design
Stage 1 Data (N=20) to be Shared Today
Combination | |||||
N = 10 | |||||
Screening | Enrollment | ||||
Monotherapy | |||||
N=10 | |||||
Randomization | Stage 1 |
Combination | ||
Potential Further | ||
Expansion | ||
Expansion | ||
N = 11 | ||
Patients who did not respond to Nstat monotherapy at Week 6 were eligible to cross over to receive combination therapy
Stage 2
6
NAVAL-1 Trial: Stage 1 Demographics for Patients with R/R EBV+ PTCL
65% of patients with ≥2 prior lines of therapy; 75% with advanced disease
Updated 07-Feb
Characteristic | Patients Enrolled in Stage 1 (N = 20*) | |
Median age (y), [range] | 69 [47-78] | |
Male / Female | 16 / 4 | |
ECOG performance status, Unknown / 0 / 1 / 2 | 1 / 4 / 14 / 1 | |
Ethnicity | ||
• | WHITE | 10 (50%) |
• | ASIAN | 7 (35%) |
• BLACK OR AFRICAN AMERICAN | 2 (10%) | |
• | NOT REPORTED | 1 ( 5%) |
Prior lines of therapy | ||
• | 1 | 7 (35%) |
• | 2 | 7 (35%) |
• | ≥3 | 6 (30%) |
Median number of prior therapies [range] | 2 [1-6] | |
Stage | ||
• | Unknown | 2 (10%) |
• | I-II | 3 (15%) |
• | III-IV | 15 (75%) |
*10 patients received combination Nstat + VGCV therapy and 10 patients received Nstat monotherapy | 7 |
Combination Nstat + VGCV Therapy Provides Substantially Greater Anti-Tumor Response Than Nstat Monotherapy
Updated 07-Feb
NAVAL-1 Stage 1 Responses by Treatment Subgroup and Analysis Population
Intent-to-Treat Population1
PTCL Treatment Subgroup | ORR | CRR |
Nstat + VGCV, Stage 1 (n=10) | 5/10 (50%) | 2/10 (20%) |
Nstat monotherapy, Stage 1 (n=10) | 1/10 (10%) | 0/10 (0%) |
Efficacy-Evaluable Population1, 2 | ||
PTCL Treatment Subgroup | ORR | CRR |
Nstat + VGCV, Stage 1 (n=7) | 5/7 (71%) | 2/7 (29%) |
Nstat monotherapy, Stage 1 (n=8) | 1/8 (13%) | 0/8 (0%) |
ORR, overall response rate; CRR, complete response rate | 8 |
1Investigator assessed; 2Eligible patients who had at least 1 post-baseline radiographic assessment |
Consistent and Robust Anti-tumor Activity Demonstrated Across Clinical Trials of Nstat + VGCV
Study 201 (Phase 1b/2 study) vs NAVAL-1 trial: Comparison of evaluable patients
Study 201: Combination | |
Nstat + VGCV Therapy1 | |
(n=13) | |
Evaluable Patients | |
(n=8) | |
Response | |
ORR | 4 (50%) |
CR | 3 (38%) |
PR | 1 |
SD | 1 |
PD | 3 |
Clinical Benefit Rate | 5 (63%) |
Data Cutoff | May 4, 2023 |
Combination | |
Nstat + VGCV Therapy | |
2024 | (n=10) |
Evaluable Patients | |
(n=7) | |
Response | |
ORR | 5 (71%) |
CR | 2 (29%) |
PR | 3 |
SD | 0 |
PD | 2 |
Clinical Benefit Rate | 5 (71%) |
Data Cutoff | Feb 7, 2024 |
CR=complete response; PR=partial response; SD=stable disease; PD=progressive disease; ORR=overall response rate, Clinical Benefit Rate=CR+PR+SD | 9 |
1Pereira et al, Hematol Transfus Cell Ther 2023 |
Combination Nstat + VGCV Therapy Resulted in 5x Greater Response Rate
Randomized comparison of combination Nstat + VGCV therapy to Nstat monotherapy (ITT population)
Updated 07-Feb
Combination Nstat + VGCV Therapy | Nstat Monotherapy |
5/10 (50%) Responses | 1 PR/10 (10%) Response |
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Viracta Therapeutics Inc. published this content on 13 April 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 15 April 2024 11:07:04 UTC.
