A Study to Assess the Safety and Efficacy of Nitric Oxide Injection Into Unresectable Solid Primary or Metastatic Tumors

A Phase 1, Open-Label, Dose Escalation and Dose Expansion Study to Assess the Safety and Efficacy of Nitric Oxide Injection Into Unresectable Solid Cutaneous/Subcutaneous Primary or Metastatic Tumors

This is a Phase 1, open-label, dose-escalation and dose-expansion study comprised of a screening period, a single treatment session, an evaluation period of 21±3 days, and safety and survival follow-up period of up to 12 weeks post-treatment.

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: Nitric Oxide 25,000 ppm; Drug: Nitric Oxide 50,000 ppm; Drug: Nitric Oxide 100,000 ppm; Drug: Nitric Oxide selected dose

Detailed Description

The purpose of this Phase 1 study is to initiate clinical development of gNO in patients with unresectable cutaneous or subcutaneous primary or metastatic solid tumors that are not amenable or have failed standard treatment, for which no therapy of proven efficacy exists, or which has progressed despite standard therapy. This study of gNO treatment will consist of 2 parts: a dose-escalation part to establish a safe and tolerable dose of gNO in patients with primary or metastatic unresectable cutaneous or subcutaneous solid tumors (Part A), and a dose expansion phase (Part B) which may be initiated at the Sponsor's discretion after the maximum tolerated dose (MTD) and/or optimal biological dose (OBD) (or recommended Phase 2 dose [RP2D]) has been determined in the dose-escalation phase (Part A). This study will be the basis for future studies.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Edith Dekel; Phone Number: 972-50-8464449; Email: edekel@beyondcancer.com
• Study Contact Backup: Name: Yaara Ber, PhD; Email: yber@beyondcancer.com

Study Locations

• Israel
  • Be'er Sheva, Israel
    • Recruiting
    • Soroka Medical Center
  • Jerusalem, Israel
    • Recruiting
    • Hadassah Ein-Karem
  • Ramat Ef'al, Israel
    • Recruiting
    • Sheba Medical Center
  • Tel Aviv, Israel
    • Recruiting
    • Sourasky Tel Aviv Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient (male or female) is at least 18 years of age at the time of signature of the informed consent form.
• Patient has an ECOG Performance Status score of 0-3 and with a life expectancy of ≥3 months.
• Patient must have a confirmed diagnosis of at least one unresectable cutaneous or subcutaneous histologically confirmed primary or metastatic solid tumor. Up to five target lesions may be identified.
• No therapy of proven efficacy exists for the tumor, the tumor is not amenable to standard therapies, the tumor has failed to respond to standard therapy or has progressed despite standard therapy.
• Patient has measurable disease on imaging based on RECIST Version 1.1.
• Patient have adequate hematologic and organ function.
• Patient have not had radiotherapy to the targeted lesions within the preceding 12 months.
• Superficial tumor axis minimum length and depth of 4.5mm. .
• Patient is not with childbearing potential or agrees to use adequate contraceptive methods

Exclusion Criteria:

• The tumor is situated in the lymph node, in thyroid, close to trachea or in facial area or other region which, in the Investigator's opinion, can pose extra risk to the patient.
• Has received prior systemic anti-cancer therapy including investigational agents within 14 days of the start of study treatment.
• Active central nervous system tumors or metastases..
• Received systemic corticosteroid therapy ≤1 week prior to study treatment or any other form of systemic immunosuppressive medication for medically significant acute or chronic conditions.
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, neuropathy and protocol-defined laboratory values.
• Active or prior documented autoimmune or inflammatory disorders.
• History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of enrolment.
• Known active infection and uncontrolled intercurrent illness.
• Receiving drugs that have contraindication with NO.
• Patient is receiving anticoagulants including low molecular weight heparin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Subjects will receive 25,000 ppm NO	Drug: Nitric Oxide 25,000 ppm; Intratumoral injection of 25,000 gNO; Other Names: gNO injection
Experimental: Cohort 2; Subjects will receive 50,000 ppm NO	Drug: Nitric Oxide 50,000 ppm; Intratumoral injection of 50000 gNO
Experimental: Cohort 3; Subjects will receive 100,000 ppm NO	Drug: Nitric Oxide 100,000 ppm; Intratumoral injection of 100,000 gNO
Experimental: RP2D Expansion; Subjects will receive the RP2D dose of NO	Drug: Nitric Oxide selected dose; Intratumoral injection of selected does on gNO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AEs, SAEs and DLTs (safety) parameters.	The incidence and characteristics of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs) and changes in assessed safety parameters. Toxicity will be graded according to NCI CTCAE version 5.0	up to12 weeks from injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor activity of a single intratumoral gNO injection at all administered doses	The anti-tumor activity of a single intratumoral gNO injection will be measured per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and secondarily immune-related RECIST (iRECIST).	up to Day 21 from injection

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of predictive biomarkers for anti-tumor activity of a single intratumoral gNO injection	Measurement of blood immune biomarkers levels	up to Day 21 from injection

Collaborators and Investigators

• Sponsor: Beyond Air Inc.
• Investigators: Study Director: David Greenberg, MD, Study Internal Medical Monitor

Publications and helpful links

Helpful Links

• Meirovitz A., et al. Phase 1 study of ultra-high concentration nitric oxide (UNO) in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies. SITC 2023
• Confino H., et al. Intratumoral administration of high-concentration nitric oxide and anti PD-1 treatment leads to higher tumor regression rates and prolonged survival in CT26 tumor-bearing mice SITC 2022

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2022
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 25, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Nitric Oxide; Intratumoral Injection; single gNO injection
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: BA-ONC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No