Safety,Tolerability,and Efficacy of VCN-01 With Durvalumab in R/M Head and Neck Squamous Cell Carcinoma

NCT03799744 | Unknown Phase 1

• 2 other identifiers: ICO-VCN-H&N-20182018-001095-38
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of VCN-01 in Combination With Durvalumab (MEDI4736) in Subjects With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck. VCN-01 is a genetically modified oncolytic adenovirus characterized by the presence of four independent genetic modifications on the backbone of the wild-type HAd5 adenovirus genome, encoding human PH20, that confer tumor selectivity and anti-tumor activity. Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that inhibits binding of PD-L1. The proposed mechanism of action (MOA) for durvalumab is interference in the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, including those that may result in tumor elimination.

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell of Head and Neck; Metastasis; Recurrence

Outcome Measures

Primary Outcomes (1)

• Safety by means of Adverse Events (AEs)

  Incidence of Adverse Events as assessed by CTCAE v4.0

  through study completion, an average of 2 years

Secondary Outcomes (15)

• Objective response rate (ORR)

  On Cycle 3 (+/- 3 days, each cycle is 28 days), and then every 2 cycles (± 7 days) until disease progression or withdrawal (an average of 2 years)

• Progression Free Survival (PFS)

  On Cycle 3 (+/- 3 days, each cycle is 28 days), and then every 2 cycles (± 7 days) until disease progression or withdrawal (an average of 2 years)

• Maximum Plasma Concentration (Cmax ) of VCN-01

  For both arms: On day 1 pre-dose (within 15 minutes prior to VCN-01 infusion) and then 30 minutes, 1, 2, 4, 6, 24 and 48 hours post VCN-01 administration.

• Tmax of VCN-01

  VCN-01 and Durvalumab concomitant arm: On day 1 pre-dose (within 15 minutes prior to VCN-01 infusion) and then 30 minutes, 1 hours, 2 hours, 4 hours, 6 hours, 24 hours and 48 hours post VCN-01 administration. VCN-01 and Durvalumab sequential: On day 1

• AUC of VCN-01

  VCN-01 and Durvalumab concomitant arm: On day 1 pre-dose (within 15 minutes prior to VCN-01 infusion) and then 30 minutes, 1 hours, 2 hours, 4 hours, 6 hours, 24 hours and 48 hours post VCN-01 administration. VCN-01 and Durvalumab sequential: On day 1

Study Arms (2)

VCN-01 and Durvalumab; concomitant.

EXPERIMENTAL

Combination VCN-01 (single iv dose) with Durvalumab, Concomitant schedule; Dose Escalation of VCN-01

Genetic: VCN-01; Biological: Durvalumab

VCN-01 and Durvalumab; sequential

EXPERIMENTAL

Combination VCN-01 (single iv dose) with Durvalumab, Delayed schedule (14 days); Dose Escalation of VCN-01

Genetic: VCN-01; Biological: Durvalumab

Interventions

VCN-01 GENETIC

Dose level 1: 3.3x10\^12 viral particles/patient and Dose level 2: 1x10\^13 viral particles/patient

VCN-01 and Durvalumab; concomitant.; VCN-01 and Durvalumab; sequential

Durvalumab BIOLOGICAL

Dose: 1500 mg Q4W

VCN-01 and Durvalumab; concomitant.; VCN-01 and Durvalumab; sequential

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization (e.g., Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures; including screening evaluations must be obtained.
• Adult subjects; age ≥ 18 years at time of study entry
• ECOG Performance status 0 or 1
• Life expectancy above 3 months
• Body weight \>30kg
• Adequate normal organ and marrow function as defined below (transfusions intended to elevate any parameters below solely for the intent of meeting study eligibility are not permitted):
• Leukocytes ≥3000 mcL
• Absolute neutrophil count ≥1500 mcL (or 1.0) x (≥ 1500 per mm3)
• Platelets ≥100 000 mcL
• Haemoglobin ≥9 g/dL
• Total bilirubin ≤1.5 x ULN; total bilirubin ≤3×ULN in patients with documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or in the presence of liver metastases
• ALT and AST ≤2.5×ULN if no demonstrable liver metastases or ≤5×ULN in the presence of liver metastases
• Creatinine ≤ 1.5 x UNL or measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (see section 4.1.).
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients (see section 4.1.).
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) within 4 weeks (28 days) prior to the first dose of study treatment. Enrolment with a shorter period of time might be allowed upon discussion with the Study Physician/Medical Monitor according data of sufficient washout time form PK properties of the agent.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Previous treatment PD1/PD-L1 inhibition (including Durvalumab) is a specific entry criterion, but patients:Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• o Exception: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy.
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
• Presently has a second malignancy other than SCCHN, or history of treatment for invasive cancer other that SCCHN in the past 3 years except for:
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Previously treated non-invasive in-situ carcinoma.
• Cervical carcinoma stage 1B or less.
• Non-invasive basal cell and squamous cell skin carcinoma.
• Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate-specific antigen, and not requiring ongoing antiandrogen hormonal therapy.
• Other malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence.
• Patients with other malignancies treated with curative intent and with no known active disease \< 3 years and at low risk of recurrence, may be eligible upon discussion with the Medical Monitor.

Sponsors & Collaborators

• Institut Català d'Oncologia: lead
• Theriva Biologics SL: collaborator
• BioClever 2005 S.L.: collaborator
• AstraZeneca: collaborator

Study Sites (2)

Institut Català D'Oncologia

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis; Recurrence

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Design

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

Model Details: This is a phase I trial, multicenter, open label, and dose escalation study. Patients will be entered at each dose level, according to a planned dose escalation schedule. Absence of unacceptable toxicity at the previous dose is required for entering a patient in the subsequent level. The investigational treatment will be a single i.v. VCN-01 dose combined with concomitant i.v. durvalumab (MEDI4736) 1500 mg Q4W (Arm I) or durvalumab starting two weeks after VCN-01 administration, "sequential schedule" (Arm II). Patient recruitment in Arm I and Arm II will be performed in parallel based on slot availability. Only one single dose of VCN-01 will be administered to each patient during the trial. Durvalumab will be administered Q4W until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion.

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: January 10, 2019
• Study Start: March 20, 2019
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: March 28, 2022

Record last verified: 2022-03

Locations

ES (2)