NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD-1 Therapy

Nanobiotix

Status and phase

Enrolling

Phase 1

Conditions

Metastasis from Malignant Tumor of Cervix

Metastasis from Malignant Tumor of Bladder (Disorder)

Metastasis from Malignant Tumor of Liver

Metastatic Renal Cell Carcinoma

Immunotherapy

Squamous Cell Carcinoma of Head and Neck

Radiotherapy

Metastatic NSCLC

Microsatellite Instability-High Solid Malignant Tumour

Metastasis from Malignant Melanoma of Skin (disorder)

Metastatic Triple-Negative Breast Carcinoma

Treatments

Drug: Pembrolizumab

Drug: Nivolumab

Radiation: SABR

Drug: NBTXR3

Study type

Interventional

Funder types

Industry

Identifiers

NCT03589339

1100

Details and patient eligibility

About

The 1100 study is an open-label, Phase I, dose escalation and expansion prospective clinical study to assess the safety of intratumoral injection of NBTXR3 activated by radiotherapy in combination with anti-PD-1 therapy.

Full description

The 1100 study aims to evaluate the safety, efficacy, and tolerability of NBTXR3 activated by radiotherapy in combination with an anti-PD-1 therapy in three cohorts of patients in dose escalation and expansion parts. The Escalation Cohort 1 includes patients with LRR or R/M HNSCC with the injectable lesion in a previously irradiated field. In Escalation Cohorts 2 and 3, patients present with lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

The Expansion cohort 1 includes patients with LRR or R/M HNSCC with the injectable lesion located either in head and neck area or in lung or liver, who are resistant to anti-PD-1 therapy. The Expansion cohort 2 includes patients with LRR or R/M HNSCC with the injectable lesion located either in head and neck area or in lung or liver, who are naive to anti-PD-1 therapy.

The Expansion Cohort 3 includes patients with inoperable NSCLC, malignant melanoma, HCC, RCC, urothelial cancer, cervical cancer or TNBC with metastases to lungs, liver or soft tissue and who are resistant to anti-PD-1 therapy.

These patients have a high unmet need and the Sponsor hypothesizes that NBTXR3 activated by radiotherapy will act synergistically with anti-PD-1 to enhance the therapeutic index of radiotherapy maximizing local effect, to overcome radio-resistance, to increase the local efficacy of immunotherapy, and to improve distant tumor control via an abscopal effect. Eligible patients will receive a single intratumoral injection of NBTXR3 subsequently activated by radiotherapy and then an approved anti-PD-1. The end of treatment visit will take place 4 weeks after the last radiotherapy fraction. Patients will be followed for long-term safety and efficacy for 2 years after the EOT visit.

Enrollment

145 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed informed consent form
Biopsy-confirmed cancer diagnosis indicated to receive anti-PD-1 therapy:

Dose Escalation:

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 non-irradiated liver field

Expansion:

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
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 exposure as follows:

Dose Escalation (all cohorts):

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 non-responder), or
Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 secondary resistance (i.e., secondary anti-PD-1 non-responder)

Expansion:

Expansion Cohorts 1 and 3: Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 primary or secondary resistance as described above
Expansion Cohort 2: Has not received prior anti-PD-1 therapy (i.e., anti-PD-1 naïve)
- Has at least one tumor lesion that can be accurately measured according to RECIST 1.1. and is amenable for intratumoral injection
- ECOG performance status 0-2
- Life expectancy >12 weeks
- Adequate organ and bone marrow function
- Negative pregnancy test ≤ 7 days prior to 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/L1 that led to the termination of the previous anti-PD-1 therapy due to intolerance or toxicity and precludes further PD-1 exposure
Symptomatic central nervous system metastases and/or carcinomatous meningitis
Active autoimmune disease that has required systemic treatment in the past 1 year
Known HIV or active hepatitis B/C infection
Active infection requiring intravenous treatment with antibiotics
Received a live virus vaccine within 30 days prior to study treatment
History of pneumonitis that required steroids or with current pneumonitis
Extensive metastatic disease burden defined as more than 5 lesions overall including the primary tumor
Locoregional recurrent HNSCC with ulceration
Has received prior therapy with a checkpoint inhibitor, within 2 weeks prior to NBTXR3 injection
Has received prior systemic anti-neoplastic therapy, including investigational agents, within 4 weeks prior to NBTXR3 injection
Has not recovered from AEs due to previous anti-neoplastic therapies and/or interventions (including radiation) to ≤ Grade 1 or baseline at screening
Clinically significant cardiac arrhythmias
Class III or IV Congestive Heart Failure as defined by the New York Heart Association functional classification system < 6 months prior to screening
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
Any condition for which participation would not be in the best interest of the participant