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

Phase 1

Recruiting

• Conditions: Cancer
• Interventions: Drug: Nitric Oxide 50,000 ppm; Drug: Nitric Oxide 100,000 ppm; Drug: Nitric Oxide selected dose; Drug: Nitric Oxide 25,000 ppm

• Registration Number: NCT05351502
• Lead Sponsor: Beyond Air Inc.

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.

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 Timeline

• Study First Submitted: 2022-04-12
• Study First Submitted QC: 2022-04-25
• Study First Posted: 2022-04-28
• Study Start: 2022-08-14
• Status Verified: 2024-07
• Last Update Submitted: 2024-08-15
• Last Update Posted: 2024-08-16
• Primary Completion: 2025-05-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 38

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2	Nitric Oxide 50,000 ppm	Subjects will receive 50,000 ppm NO
Cohort 3	Nitric Oxide 100,000 ppm	Subjects will receive 100,000 ppm NO
RP2D Expansion	Nitric Oxide selected dose	Subjects will receive the RP2D dose of NO
Cohort 1	Nitric Oxide 25,000 ppm	Subjects will receive 25,000 ppm NO

Primary Outcome Measures

Name	Time	Method
Incidence of AEs, SAEs and DLTs (safety) parameters.	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

Name	Time	Method
Anti-tumor activity of a single intratumoral gNO injection at all administered doses	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).

Trial Locations

Locations (4)

Soroka Medical Center; 🇮🇱 Be'er Sheva, Israel

Sheba Medical Center; 🇮🇱 Ramat Ef'al, Israel

Hadassah Ein-Karem; 🇮🇱 Jerusalem, Israel

Sourasky Tel Aviv Medical Center; 🇮🇱 Tel Aviv, Israel