Clinical trial NCT05351502: A Study to Assess the Safety and Efficacy of Nitric Oxide Injection Into Unresectable Solid Primary or Metastatic Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cancer
Keywords: Intratumoral Injection
Nitric Oxide
single gNO injection
Lead sponsor: Beyond Air Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-28
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Incidence of AEs, SAEs and DLTs (safety) parameters.
timeFrame: up to12 weeks from injection
Secondary outcomes:
measure: Anti-tumor activity of a single intratumoral gNO injection at all administered doses
timeFrame: up to Day 21 from injection
Other outcomes:
measure: Assessment of predictive biomarkers for anti-tumor activity of a single intratumoral gNO injection
timeFrame: up to Day 21 from injection
Locations:
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein-Karem
city: Ramat Ef'al
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Tel Aviv Medical Center
Study officials:
affiliation: Study Internal Medical Monitor
name: David Greenberg, MD
role: STUDY_DIRECTOR
References: