Phase 1/2a Study of VK-2019 in Patients With Epstein-Barr Virus (EBV)-Positive Nasopharyngeal Carcinoma (NPC)

NCT03682055 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: VK-2019-001
• Study Type: interventional
• Target: 14
• Locations: 5 countries
• Sites: 6

Brief Summary

VK-2019-001 is a 1/2a trial of the oral EBNA-1 targeting agent VK-2019 in patients with EBV-positive recurrent or metastatic NPC to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D), as well as to evaluate the PK profile of VK-2019.

Conditions

Nasopharyngeal Carcinoma; Nasopharyngeal Cancer

Keywords

Epstein-Barr Virus; Nasopharyngeal Carcinoma; NPC; EBV; EBNA1 inhibitor; VK-2019; Nasopharynx cancer; Nasopharynx carcinoma

Outcome Measures

Primary Outcomes (1)

• All Cohorts: The Frequency, Severity, and Duration of AEs and DLTs, AEs Leading to Discontinuation, and AEs Leading to Death.

  24 months

Secondary Outcomes (1)

• Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR

  24 months

Study Arms (4)

Phase 1 Dose Escalation (Accelerated Titration)

EXPERIMENTAL

VK-2019 QD in Accelerated Titration dose escalation cohorts enrolling EBV+ NPC

Drug: VK-2019

Phase 1 Dose Escalation (Rolling Six)

EXPERIMENTAL

VK-2019 QD in Rolling Six dose escalation cohorts enrolling EBV+ NPC.

Drug: VK-2019

Phase 1 Dose Expansion(s)

EXPERIMENTAL

VK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified criteria for clinical and/or biological activity.

Drug: VK-2019

Phase 2a Dose Expansion(s)

EXPERIMENTAL

VK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified efficacy criteria in Phase 1 Dose Escalation cohorts.

Drug: VK-2019

Interventions

VK-2019 DRUG

EBNA1 inhibitor

Phase 1 Dose Escalation (Accelerated Titration); Phase 1 Dose Escalation (Rolling Six); Phase 1 Dose Expansion(s); Phase 2a Dose Expansion(s)

Eligibility Criteria

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

You may qualify if:

• Informed consent obtained prior to any protocol mandated assessment.
• Age ≥ 18.
• Either loco regionally recurrent or metastatic EBV positive nasopharyngeal carcinoma not amenable to curative treatment. EBV positivity is defined as high EBV viral load in plasma (\> 4000 genomes per µg plasma DNA) and/or biopsy tissue positive for EBV.
• Prior palliative radiation must have been completed at least 2 weeks prior to study Cycle 1 Day 0.
• Prior anti cancer systemic treatment must have been completed greater than 4 weeks prior to study Cycle 1 Day 0.
• Toxicities related to prior anti-cancer therapy must have returned to Grade 1 or less. Peripheral neuropathy must be Grade 2 or less. Chronic but stable toxicities Grade \> 1 (e.g., dysphasia, G tube dependence, etc.) may be allowed after agreement between the Investigator and Sponsor.
• For the dose expansion phase only: Patients must have RECIST v1.1 measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non nodal lesions and short axis for nodal lesions) as ≥ 10 mM with spiral CT scan, MRI, or calipers by clinical exam.
• ECOG performance status score of ≤ 2 at study entry.
• Absolute neutrophil count \> 1500/µL (stable off any growth factor within 1 week of study drug administration).
• Hemoglobin \> 9g/dL (transfusion to achieve this level is permitted).
• Platelet count \> 75 x 103/ µL (transfusion to achieve this level is NOT permitted).
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN).
• Total serum bilirubin ≤ 1.5 x ULN.
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min as calculated per Cockcroft Gault equation.
• Urinary protein \< 2+ by dipstick. If dipstick ≥ 2+, then a 24 hour urine collection can be done and the patient may enter only if urinary protein is \< 1 g/24 hour.

You may not qualify if:

• Severe or active symptomatic cardiopulmonary diseases (unstable angina and/or congestive heart failure or peripheral vascular disease within the last 12 months; chronic obstructive pulmonary disease exacerbation other respiratory illness requiring hospitalization) or clinically significant psychiatric disorders; patients with effectively treated conditions (eg, stenting for CAD) are eligible.
• Metastatic disease with active central nervous system (CNS) involvement, defined as parenchymal brain involvement. Patients with cranial nerve or base of skull involvement without the above are eligible; Patients with CNS metastases stable 1 month following focal treatment with radiation are eligible.
• Concurrent treatment with systemic cancer directed therapy including complementary, alternative, herbal or nutritional supplement based treatments whose purpose is for anti cancer effect.
• Positive for human immunodeficiency virus (HIV) are not excluded from this study, but HIV positive patients must have:
• A stable regimen of highly active anti retroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
• A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR based test
• Serious uncontrolled medical disorder or active infection which would, in the opinion of the Investigator, impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
• Currently taking drugs that inhibit or induce OATP1B1 or OATP1B3 within 5 half lives of that agent. Examples are included in Appendix 2.
• Have received a prior organ allograft or allogeneic bone marrow transplant.
• Current non prescription drug or alcohol dependence.
• For all female patients, pregnancy or breastfeeding.
• All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study.
• Corrected QT by Fridericia's formula (QTcF) of \> 470 ms.

Sponsors & Collaborators

• Cullinan Therapeutics Inc.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Stanford University, School of Medicine, Stanford Cancer Institute

Stanford, California, 94305, United States

Location

The University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Sun Yat Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Hong Kong University - Queen Mary Hospital

Hong Kong, Hong Kong

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Related Publications (3)

• Young LS. Epstein-Barr virus at 50-future perspectives. Chin J Cancer. 2014 Nov;33(11):527-8. doi: 10.5732/cjc.014.10208.

  PMID: 25367333 BACKGROUND

• Young LS, Dawson CW. Epstein-Barr virus and nasopharyngeal carcinoma. Chin J Cancer. 2014 Dec;33(12):581-90. doi: 10.5732/cjc.014.10197. Epub 2014 Nov 21.

  PMID: 25418193 BACKGROUND

• Tsao SW, Tsang CM, Lo KW. Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond B Biol Sci. 2017 Oct 19;372(1732):20160270. doi: 10.1098/rstb.2016.0270.

  PMID: 28893937 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Results Point of Contact

• Title: Phill Gallacher
• Organization: Cullinan Oncology

pgallacher@cullinanoncology.com

+1 617 710 9127

Study Officials

• A. Dimitrios Colevas, MD

  Stanford Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: September 24, 2018
• Study Start: April 4, 2019
• Primary Completion: June 23, 2020
• Study Completion: August 8, 2020
• Last Updated: August 15, 2023
• Results First Posted: August 15, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); CN (1); US (2); HK (1); SG (1)