Nadunolimab to prevent progression of high-risk lung nodules

A Phase 2 Trial of Nadunolimab for Current or Former Smokers With High-risk Lung Nodules.

This trial will test whether nadunolimab can shrink or stop growth of multifocal part-solid high-risk lung nodules in current or former heavy smokers (≥20 pack‑years).

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 59 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (other)
• Drugs / interventions: prednisone, nadunolimab
• Locations: 1 site (New York, New York)
• Trial ID: NCT07284485 on ClinicalTrials.gov

What this trial studies

This single-arm phase 2 Simon's optimal two-stage trial administers nadunolimab as an immunoprevention strategy for adults with multifocal part-solid high-risk lung nodules who are current or former smokers (≥20 pack‑years). Stage 1 will enroll 20 participants and will expand to an additional 36 only if at least two early responses are observed and the sponsor obtains FDA approval of an amendment with initial safety data, for a planned total of 56 participants. The primary activity measure is documented regression of at least one high-risk part-solid nodule without significant dose-limiting toxicity, with participants followed by serial CT imaging and blood draws. Participants may be followed for up to five years and statistical comparisons will be made against historical controls using pre-specified Simon two-stage thresholds.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) who are current or former tobacco smokers with ≥20 pack‑years, have ≥2 multifocal part-solid nodules (at least one with solid component <9 mm) showing progression on at least one annual CT, are not surgical candidates, and have ECOG performance status 0–1.

Not a fit: Patients who are surgical candidates, have single or non–part-solid nodules, have <20 pack‑years smoking history, poor performance status, or established invasive lung cancer are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, nadunolimab could shrink or halt growth of high-risk lung nodules, lowering the risk of progression to invasive lung cancer and reducing the need for invasive treatments.

How similar studies have performed: Using immune-based drugs to prevent progression of high‑risk lung nodules is relatively novel with limited prior data, so this approach remains largely experimental and unproven in large trials.

Eligibility criteria

Inclusion Criteria:

* Participants must be current or former tobacco smokers (\>20 pack years)
* Participants must have multi-focal part-solid nodules (\>2 lesions, at least one with solid component \<9mm) with evidence of progression on at least one annual follow-up CT scan.
* Participants must not meet criteria for surgical intervention at the time of enrollment.
* Patient must be willing and able to provide blood samples (12 green-top tubes, roughly 100mL) at the five time points indicated in the Study Calendar.
* Age ≥ 18 years.
* ECOG 0-1. The exception will be Participants carrying long term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy. This must be documented in screening clinic visit note by investigator.
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 1 month and 6 months following completion of therapy, for woman and men, respectively. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  * Has not undergone a hysterectomy or bilateral oophorectomy; or
  * Has not been naturally postmenopausal for at least 24 consecutive months
* Ability to understand and the willingness to sign a written informed consent.
* Adequate organ and marrow function as defined below:

  * Hematologic
  * \- Absolute neutrophil count (ANC) ≥1,500 /mcL
  * \- Platelets ≥100,000 /mcL
  * \- Hemoglobin ≥9 g/dL
  * Renal\*
  * \- Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated (calculated per institutional standard) creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min GFR for patient with creatinine levels \> 1.5 X institutional ULN
  * Hepatic\*
  * \- Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for
  * \- Participants with total bilirubin levels \> 1.5 ULN
  * \- AST or ALT ≤ 2.5 X ULN
  * \- Albumin \>2.5 mg/dL

    * If laboratory criteria are not met due to what the investigator determines to be a biologic cause (e.g. Gilbert's syndrome causing elevated bilirubin or excessive muscle mass affecting creatinine) or drug-related cause (e.g. elevating in transaminases due to HAART therapy, elevated INR due to anticoagulation) then the specific lab values will not be used to exclude patient from this trial. This determination will be made by PI.

Exclusion Criteria:

* Any pulmonary nodule with a solid component \>8mm.
* Patients may not be receiving any other investigational agents at the time of enrollment.
* Uncontrolled intercurrent illness prior to starting therapy including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Exception: Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
* Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Exception: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
* Known HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with \<200 CD4+ T cells/microliter in the peripheral blood. HIV testing is not required for patients with no known history of HIV.
* Has known Hepatitis B or active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). HBV and HCV testing is not required for patients with no known history of these viruses.
* History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
* Receipt of a live vaccine, etanercept, or tumor necrosis factor-alpha inhibitors within 30 days of planned start of study drug
* Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps)Principal investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient.

Where this trial is running

New York, New York

• Icahn School of Medicine at Mount Sinai — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Robert M Samstein, MD, PhD — Icahn School of Medicine at Mount Sinai
• Study coordinator: Lisa Fitzgerald

Conditions: High-risk Lung Nodules, High-risk Lung nodules, Nadunolimab, immunoprevention, tobacco smokers 20 pack-years, multi-focal part-solid nodules, immunomodulatory compounds