CancerPhase 1NCT05351502
A Study to Assess the Safety and Efficacy of UNO - Ultra High Concentration Nitric Oxide Injection in Combination With PD-1 Inhibitors Into Unresectable Solid Primary or Metastatic Tumors
A Phase 1 study testing Nitric Oxide 25,000 ppm and Nitric Oxide 50,000 ppm in people with Cancer, run by Beyond Air Inc. at 4 sites in Israel.
Trial summary
This is a Phase 1, open-label, dose-escalation and dose-expansion study comprised of 2 parts: Phase 1a - 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, and Phase 1b - a single treatment session followed by PD-1 inhibitors… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- Nitric Oxide 25,000 ppm and Nitric Oxide 50,000 ppm
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 4 sitesIsrael
- Study dates
- 14 Aug 2022to 31 Aug 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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. (non-measurable disease acceptable in Phase 1a)
- Patient have adequate hematologic and organ function.
Show all 16Show fewer
- Patient have not had radiotherapy to the targeted lesions within the preceding 12 months.
- Superficial tumor axis minimum length and depth of 4.5mm and must have a superficial region that can be fully traversed with a 32 mm-long needle with a 4.5 mm minimum depth. This criterion applies only for Phase 1a. .
- Patient is not with childbearing potential or agrees to use adequate contraceptive methods
- Phase 1b specific Inclusion Criteria:
- Tumor types include, but not limited to, metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC), unresectable or metastatic melanoma, high risk early-stage triple negative breast cancer or locally recurrent unresectable or metastatic breast cancer, and subjects with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC, basal cell carcinoma, merkel cell carcinoma, classical Hodgkin lymphoma (cHL) and primary mediastinal large B-cell lymphoma (PMBCL), amendable to UNO administration, with cutaneous or subcutaneous lesions, will enroll to receive the combination therapy.
- Superficial tumor axis of a 4.5 mm minimum length and depth; or accessible peripheral lymph node-based Investigator's judgement.
- Previously received PD-1 directed immunotherapy and had either
- Refractory to PD-1
- Relapsed on single agent PD-1
- Prolonged stable disease on single agent PD-1 ≥ 12 weeks
Who cannot join
- The tumor is situated in the lymph node (Phase 1a only), 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.
- The level of tumor vascularity was determined by the central radiologist, to pose a considerable risk for penetrating blood vessels during insertion of a 23G needle to the tumor.
- 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.
Show all 11Show fewer
- Active or prior documented autoimmune or inflammatory disorders - according to the discretion of the PI.
- 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 - according to the discretion of the PI.
- Receiving drugs that have contraindication with NO.
- Patient is receiving anticoagulants including low molecular weight heparin.
Trial locations and contacts
4 sites in 1 country.
Israel4 sites
Soroka Medical Center
Beersheba
Hadassah Ein-Karem
Jerusalem
Sheba Medical Center
Ramat Ef‘al
Sourasky Tel Aviv Medical Center
Tel Aviv
About this study
Official title: A Phase 1, Open-Label, Dose Escalation and Dose in Combination With PD-1 Inhibitors Expansion Study to Assess the Safety and Efficacy of UNO - Ultra High Concentration 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 2 parts: Phase 1a - 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, and Phase 1b - a single treatment session followed by PD-1 inhibitors treatment cycles, in PD-1 single agent progressors, to evaluate safety, overall response rate, duration of response, progression free survival, and overall survival follow-up until disease progression or death.
Read the detailed description
The purpose of this Phase 1 study is to initiate clinical development of UNO 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 UNO treatment will consist of 2 parts: a dose-escalation part to establish a safe and tolerable dose (maximum tolerate dose [MTD] and/or optimal biological dose [OBD] leading to a recommended Phase 2 dose [RP2D]) of UNO in patients with primary or metastatic unresectable cutaneous or subcutaneous solid tumors (Phase 1a), and a dose expansion phase of 25,000 ppm in combination with PD-1 inhibitor (Phase 1b) which may be initiated at the Sponsor's discretion in parallel with the Phase 1a. This study will be the basis for future studies.
- Conditions
- Cancer
- Being tested
- Nitric Oxide 25,000 ppm, Nitric Oxide 50,000 ppm
- Keywords
- Intratumoral Injection, Nitric Oxide, Single UNO injection, PD-1 Inhibitors, Immunotherapy, Combination Immunotherapy
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric Oxide 25,000 ppmDrug
Also called UNO injection
Intratumoral injection of 25,000 UNO
Nitric Oxide 50,000 ppmDrug
Intratumoral injection of 50000 UNO
Nitric Oxide 25,000 ppmDrug
Intratumoral injection of UNO followed by PD-1 inhibitor treatment cycles
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects will receive 25,000 ppm UNO Receives: Drug: Nitric Oxide 25,000 ppm |
| Cohort 2 | Experimental | Subjects will receive 50,000 ppm UNO Receives: Drug: Nitric Oxide 50,000 ppm |
| Dose Expansion | Experimental | Subjects will receive 25,000 ppm UNO in combination with PD-1 inhibitor treatment cycles Receives: Drug: Nitric Oxide 25,000 ppm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1b: Overall response rate per RECIST version 1.1 and (iRECIST)
The incidence of the following parameters at the end of every even cycle: Stable disease (SD), partial response (PR), complete response (CR) or confirmed disease progression (PD) - status at the treatment site, preliminary anti-tumor activity on injected and non-injected lesions. Time to treatment response, duration of response.
Measured: until disease progression or up to 3 months
Phase 1a: Incidence AEs, SAEs and DLTs.
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
Measured: Up to 12 weeks from UNO injection
Secondary outcomes (4)
Phase 1a: 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).
Measured: up to Day 21 from UNO injection
Phase 1b: To assess progression free survival (PFS) and overall survival (OS).
Progression free survival and overall survival at Months 3, 6, 9, and 12 months.
Measured: up to 12 months from UNO injection
Phase 1b: 2. To assess the clinical benefit rate (CBR: CR +PR+SD ≥ 6 months), time to response (TTR) by RECIST and iRECIST.
Clinical benefit rate (CBR: CR+PR+SD ≥ 6 months), time to response (TTR) by RECIST and iRECIST.
Measured: up to 12 months from UNO injection
Phase 1b: To assess incidence and severity of non-serious adverse events and serious adverse events, including immune related adverse events (irAEs).
Incidence and severity of non-serious adverse events and serious adverse events, including irAEs.
Measured: Up to disease progression or up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2022
- Study start14 Aug 2022
- Primary completion31 Aug 2025
- Study completion31 Aug 2025
Why it stopped: study stopped due to changes of sponsor strategy and resource allocation. No safety issues were identified
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- In Phase 1a, the following UNO doses will be studied to determine MTD and/or OBD: 25,000 ppm and 50,000 ppm. Additional dose levels may be evaluated based on the emerging data as determined by the Safety Review Committee. In Phase 1b, subjects will be treated with 25,000 ppm, in combination with PD-1 inhibitor treatment cycles.
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beyond Air Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Greenberg, MD, Study director, Study Internal Medical Monitor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05351502
- Sponsor's protocol ID
- BA-ONC-01
- Status last verified
- Oct 2026
- First submitted
- 12 Apr 2022
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Dose Escalation and Dose in Combination With PD-1 Inhibitors Expansion Study to Assess the Safety and Efficacy of UNO - Ultra High Concentration Nitric Oxide Injection Into Unresectable Solid Cutaneous/Subcutaneous Primary or Metastatic Tumors
- ClinicalTrials.gov ID
- NCT05351502
- Acronym / sponsor ID
- BA-ONC-01
- Conditions
- Cancer
- Keywords
- Intratumoral Injection, Nitric Oxide, Single UNO injection, PD-1 Inhibitors, Immunotherapy, Combination Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: study stopped due to changes of sponsor strategy and resource allocation. No safety issues were identified
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Beyond Air Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Aug 2022 (actual)
- Primary completion
- 31 Aug 2025 (actual)
- Study completion
- 31 Aug 2025 (actual)
- First posted
- 28 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1, open-label, dose-escalation and dose-expansion study comprised of 2 parts: Phase 1a - 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, and Phase 1b - a single treatment session followed by PD-1 inhibitors treatment cycles, in PD-1 single agent progressors, to evaluate safety, overall response rate, duration of response, progression free survival, and overall survival follow-up until disease progression or death.
Detailed description
The purpose of this Phase 1 study is to initiate clinical development of UNO 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 UNO treatment will consist of 2 parts: a dose-escalation part to establish a safe and tolerable dose (maximum tolerate dose [MTD] and/or optimal biological dose [OBD] leading to a recommended Phase 2 dose [RP2D]) of UNO in patients with primary or metastatic unresectable cutaneous or subcutaneous solid tumors (Phase 1a), and a dose expansion phase of 25,000 ppm in combination with PD-1 inhibitor (Phase 1b) which may be initiated at the Sponsor's discretion in parallel with the Phase 1a. This study will be the basis for future studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- In Phase 1a, the following UNO doses will be studied to determine MTD and/or OBD: 25,000 ppm and 50,000 ppm. Additional dose levels may be evaluated based on the emerging data as determined by the Safety Review Committee. In Phase 1b, subjects will be treated with 25,000 ppm, in combination with PD-1 inhibitor treatment cycles.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Nitric Oxide 25,000 ppmSubjects will receive 25,000 ppm UNO |
| Cohort 2 | Experimental | Drug: Nitric Oxide 50,000 ppmSubjects will receive 50,000 ppm UNO |
| Dose Expansion | Experimental | Drug: Nitric Oxide 25,000 ppmSubjects will receive 25,000 ppm UNO in combination with PD-1 inhibitor treatment cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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. (non-measurable disease acceptable in Phase 1a)
Key exclusion criteria (11 listed)
- The tumor is situated in the lymph node (Phase 1a only), 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.
- The level of tumor vascularity was determined by the central radiologist, to pose a considerable risk for penetrating blood vessels during insertion of a 23G needle to the tumor.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitric Oxide 25,000 ppmAlso: UNO injectionIntratumoral injection of 25,000 UNO | Drug | Cohort 1 |
| Nitric Oxide 50,000 ppmIntratumoral injection of 50000 UNO | Drug | Cohort 2 |
| Nitric Oxide 25,000 ppmIntratumoral injection of UNO followed by PD-1 inhibitor treatment cycles | Drug | Dose Expansion |
Primary outcome
Phase 1b: Overall response rate per RECIST version 1.1 and (iRECIST)
Time frame: until disease progression or up to 3 months
The incidence of the following parameters at the end of every even cycle: Stable disease (SD), partial response (PR), complete response (CR) or confirmed disease progression (PD) - status at the treatment site, preliminary anti-tumor activity on injected and non-injected lesions. Time to treatment response, duration of response.
Phase 1a: Incidence AEs, SAEs and DLTs.
Time frame: Up to 12 weeks from UNO 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
4 secondary outcomes
Phase 1a: Anti-tumor activity of a single intratumoral gNO injection at all administered doses
Time frame: up to Day 21 from UNO injection
Phase 1b: To assess progression free survival (PFS) and overall survival (OS).
Time frame: up to 12 months from UNO injection
Phase 1b: 2. To assess the clinical benefit rate (CBR: CR +PR+SD ≥ 6 months), time to response (TTR) by RECIST and iRECIST.
Time frame: up to 12 months from UNO injection
Phase 1b: To assess incidence and severity of non-serious adverse events and serious adverse events, including immune related adverse events (irAEs).
Time frame: Up to disease progression or up to 3 months
Results and safety
The study was stopped early (reason given: study stopped due to changes of sponsor strategy and resource allocation. No safety issues were identified). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- 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 2023Link provided by the sponsor.
- 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 2022Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Greenberg, MD study director
Study Internal Medical Monitor
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nitric Oxide 25,000 ppm and Nitric Oxide 50,000 ppm in people with Cancer, run by Beyond Air Inc. at 4 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: study stopped due to changes of sponsor strategy and resource allocation. No safety issues were identified). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1b: Overall response rate per RECIST version 1.1 and (iRECIST) (time frame: until disease progression or up to 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.