Clinical Trial 20026

• Overview

  Study Title:

  A Phase I Study of NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD1 Therapy

  Summary:

  The purpose of this research study is to determine the safe recommended dose/s and the effectiveness of intratumoral/intralesional injection of NBTXR3 activated by radiotherapy in combination with an anti-PD1 Antibody

  Objective:

  To determine the Maximum Tolerated Dose/s and the early Dose Limiting Toxicities (DLT) of intratumoral/intralesional injection of NBTXR3 activated by SABR in combination with an anti-PD1 antibody. To determine the Recommended Dose/s of NBTXR3 given as intratumoral/Intralesional injection and activated by SABR in combination with an anti-PD1 antibody, in patients with: o Locoregionally recurrent or metastatic HNSCC amenable to re-irradiation (RD1), o Lung metastasis from HNSCC (not amenable to reirradiation if synchronous locoregional recurrence and metastasis) or NSCLC (not previously irradiated) (RD2), o Liver metastasis from HNSCC (not amenable to reirradiation if synchronous locoregional recurrence and metastasis) or NSCLC (not previously irradiated) (RD3).

• Treatments

  Therapies:

  Immunotherapy; Radiotherapy; Therapy (NOS)

  Medications:

  Alimta (Pemetrexed); BMS-936558 (Nivolumab); NBTXR3 (); Nivolumab (Opdivo); Pembrolizumab (Keytruda); Pemetrexed ()

• Inclusion Criteria

  • Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for the study, and is willing to participate in the study
  • Age 18 years or older
  • Biopsy-confirmed advanced/unresectable malignant solid tumor diagnosis indicated to receive an FDA approved anti-PD-1 therapy that:
  • a. Escalation Cohort 1: Is inoperable LRR with tumor in previously irradiated HN field that is amenable to re-irradiation or R/M HNSCC with tumor in previously irradiated HN field that is amenable to re-irradiation, or
  • Escalation Cohort 2: Has metastasized to the lung (including involved lymph nodes) with tumor in a previously non-irradiated lung field, or Escalation Cohort 3: Has metastasized to the liver with tumor in a previously nonirradiated liver field
  • Expansion:
  • a. Expansion Cohorts 1 and 2: Is inoperable LRR or R/M HNSCC with at least one lesion that is amenable to irradiation within head and neck region, lung or liver
  • b. Expansion Cohort 3: Is inoperable solid tumor that has metastasized to soft tissues, lung (including mediastinal lymph nodes) or liver with at least one lesion that is amenable to irradiation
  • Prior anti-PD-1 expose as follows:
  • Dose Escalation (all chohorts):
  • Has not received prior anti-PD-1 therapy (i.e., anti-PD-1 naïve), or Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 primary resistance (i.e., primary anti-PD-1 nonresponder)
  • Has received prior anti-PD-1/PDL-1 therapy and meets criteria consistent with anti-PD-1 secondary resistance
  • Has at least one tumor lesion that can be accurately measured according to RECIST 1.1. and is amenable for intratumoral injection and for radiotherapy, as determined by the study investigator
  • ECOG performance status of 0-2
  • Life expectancy >12 weeks
  • Adequate organ and bone marrow function as defined by the protocol
  • Negative pregnancy test less than or equal to 7 days of NBTXR3 injection in all female participants of child-bearing potential.

• Exclusion Criteria

  • History of immune-related adverse events related to administration of anti-PD-1 or known hypersensitivity (Grade ≥3) to any excipients
  • Symptomatic central nervous system metastases and/or carcinomatous meningitis a. Participants with previously treated brain metastases may participate provided the brain metastases are radiologically stable, (i.e., without evidence of progression for at least 4 weeks by repeat imaging at screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to NBTXR3 injection.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) a. Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement [≤10 mg prednisone per day of equivalent] therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment 4. Known human immunodeficiency virus (HIV), active hepatitis B, or active hepatitis C infection
  • Has an active infection requiring systemic treatment
  • Received live virus vaccine ≤30 days prior to beginning study treatment
  • History of pneumonitis that required steroids or current pneumonitis
  • Extensive metastatic disease burden considered to be unamenable for radiation treatment, as determined by the study investigator
  • Locoregional recurrent HNSCC or soft tissue lesion intended for injection with skin ulceration that may, in the opinion of the investigator, increase the risk of severe tumor bleeding or breakage.
  • Has received prior therapy with a checkpoint inhibitor (e.g., anti-CTLA-4, anti-PD-1, anti-PD-L1, and/or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) within 4 weeks prior to NBTXR3 injection.
  • Has received prior systemic anti-neoplastic therapy, including investigational agents, within 4 weeks prior to NBTXR3 injection a. Note: a reduced washout window may be considered for therapies with short half-lives (e.g., kinase inhibitors) after discussion with the Sponsor
  • Has not recovered from AEs due to previous anti-neoplastic therapies and/or interventions (including radiation and immunotherapy) to ≤ Grade 1 or baseline at screening a. Note: Participants with alopecia, thyroid dysfunction or >Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second or third degree atrioventricular heart block without a permanent pacemaker in place)
  • Class III or IV Congestive Heart Failure as defined by the New York Heart Association functional classification system >A pregnant or nursing female, or women of child-bearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception starting from signed ICF through 150 days after last anti-PD-1 dose
  • Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

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