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Clinical Trial 20026

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT03589339

Phase: Phase I/II
Principal Investigator: Yang, George

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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 NSCLC, malignant melanoma, HCC, RCC, urothelial cancer, cervical cancer, TNBC 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 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 with ulceration

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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