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

• ClinicalTrials.gov Identifier: NCT05351502
• Recruitment Status: Recruiting
• First Posted: April 28, 2022
• Last Update Posted: April 2, 2024
• Sponsor: Beyond Air Inc.
• Information provided by (Responsible Party): Beyond Air Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cancer	Drug: Nitric Oxide 25,000 ppm; Drug: Nitric Oxide 50,000 ppm; Drug: Nitric Oxide 100,000 ppm; Drug: Nitric Oxide selected dose	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 38 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment

Intervention Model Description

In Part A, the following gNO doses will be studied to determine MTD and/or OBD: 25,000 ppm, 50,000 ppm and 100,000 ppm. Additional dose levels may be evaluated based on the emerging data as determined by the Safety Review Committee.

Once the MTD and/or OBD is determined, additional patients will be treated in Part B Dose Expansion to further characterize the safety and biomarkers of gNO and determine RP2D.

• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 14, 2022
• Estimated Primary Completion Date: July 1, 2024
• Estimated Study Completion Date: April 1, 2025

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Incidence of AEs, SAEs and DLTs (safety) parameters. [ Time Frame: up to12 weeks from injection ]
   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

Secondary Outcome Measures :

1. Anti-tumor activity of a single intratumoral gNO injection at all administered doses [ Time Frame: up to Day 21 from injection ]
   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).

Other Outcome Measures:

1. Assessment of predictive biomarkers for anti-tumor activity of a single intratumoral gNO injection [ Time Frame: up to Day 21 from injection ]
   Measurement of blood immune biomarkers levels

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Edith Dekel; 972-50-8464449; edekel@beyondcancer.com

Contact: Yaara Ber, PhD; yber@beyondcancer.com

Locations

Israel

Soroka Medical Center; Recruiting

Be'er Sheva, Israel

Hadassah Ein-Karem; Recruiting

Jerusalem, Israel

Sheba Medical Center; Recruiting

Ramat Ef'al, Israel

Sourasky Tel Aviv Medical Center; Recruiting

Tel Aviv, Israel

Sponsors and Collaborators

Beyond Air Inc.

Investigators

• Study Director: David Greenberg, MD; Study Internal Medical Monitor

More Information

Additional Information:

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 

• Responsible Party: Beyond Air Inc.
• ClinicalTrials.gov Identifier: NCT05351502
• Other Study ID Numbers: BA-ONC-01
• First Posted: April 28, 2022
• Last Update Posted: April 2, 2024
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Beyond Air Inc.:

Intratumoral Injection; Nitric Oxide; single gNO injection

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Nitric Oxide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Endothelium-Dependent Relaxing Factors; Vasodilator Agents; Gasotransmitters; Protective Agents