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

NCT05351502 | Recruiting Phase 1 DMC

• 1 other identifier: BA-ONC-01
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

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.

Conditions

Cancer

Keywords

Intratumoral Injection; Nitric Oxide; single gNO injection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Anti-tumor activity of a single intratumoral gNO injection at all administered doses

  up to Day 21 from injection

Other Outcomes (1)

• Assessment of predictive biomarkers for anti-tumor activity of a single intratumoral gNO injection

  up to Day 21 from injection

Study Arms (4)

Cohort 1

EXPERIMENTAL

Subjects will receive 25,000 ppm NO

Drug: Nitric Oxide 25,000 ppm

Cohort 2

EXPERIMENTAL

Subjects will receive 50,000 ppm NO

Drug: Nitric Oxide 50,000 ppm

Cohort 3

EXPERIMENTAL

Subjects will receive 100,000 ppm NO

Drug: Nitric Oxide 100,000 ppm

RP2D Expansion

EXPERIMENTAL

Subjects will receive the RP2D dose of NO

Drug: Nitric Oxide selected dose

Interventions

Nitric Oxide 25,000 ppm DRUG

Intratumoral injection of 25,000 gNO

Also known as: gNO injection

Cohort 1

Nitric Oxide 50,000 ppm DRUG

Intratumoral injection of 50000 gNO

Cohort 2

Nitric Oxide 100,000 ppm DRUG

Intratumoral injection of 100,000 gNO

Cohort 3

Nitric Oxide selected dose DRUG

Intratumoral injection of selected does on gNO

RP2D Expansion

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beyond Air Inc.: lead

Study Sites (4)

Soroka Medical Center

Beersheba, Israel

RECRUITING

Hadassah Ein-Karem

Jerusalem, Israel

RECRUITING

Sheba Medical Center

Ramat Ef‘al, Israel

RECRUITING

Sourasky Tel Aviv Medical Center

Tel Aviv, Israel

RECRUITING

Related 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

MeSH Terms

Conditions

Neoplasms

Study Officials

• David Greenberg, MD

  Study Internal Medical Monitor

  STUDY DIRECTOR

Central Study Contacts

Edith Dekel

CONTACT

972-50-8464449; edekel@beyondcancer.com

Yaara Ber, PhD

CONTACT

yber@beyondcancer.com

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: April 12, 2022
• First Posted: April 28, 2022
• Study Start: August 14, 2022
• Primary Completion: May 30, 2025
• Study Completion: June 30, 2025
• Last Updated: August 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (4)