Clinical trial NCT03589339: NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD-1 Therapy
Official title: A Phase I Dose Escalation / Dose Expansion Study of NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD-1 Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Radiotherapy
Immunotherapy
Microsatellite Instability-High Solid Malignant Tumour
Metastasis from Malignant Tumor of Liver
Squamous Cell Carcinoma of Head and Neck
Metastasis from Malignant Tumor of Cervix
Metastatic Renal Cell Carcinoma
Metastasis from Malignant Melanoma of Skin (disorder)
Metastatic Triple-Negative Breast Carcinoma
Metastatic NSCLC
Metastasis from Malignant Tumor of Bladder (Disorder)
Keywords: Oral Cavity Cancer
Oropharynx Cancer
Lung Metastasis
Liver Metastasis
Lead sponsor: Nanobiotix
Sponsor class: INDUSTRY
First posted: 2018-07-17
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

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

Dose Escalation:

1. 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
2. Escalation Cohort 2: Has metastasized to the lung (including involved lymph nodes) with tumor in a previously non-irradiated lung field, or
3. Escalation Cohort 3: Has metastasized to the liver with tumor in a previously non-irradiated liver field

Expansion:

1. 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
2. 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):

1. Has not received prior anti-PD-1 therapy (i.e., anti-PD-1 naïve), or
2. 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
3. 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:

1. 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
2. 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

Primary outcomes:
measure: [Dose Escalation Part]: Determination of the Recommended Dose
timeFrame: 24 Months
measure: [Dose Expansion Part]: Safety Evaluation at RP2D
timeFrame: 24 Months
Secondary outcomes:
measure: Evaluation of the anti-tumor response of R3/RT/PD-1
timeFrame: 24 months
measure: Assessment of the safety and feasibility of R3/RT/PD-1
timeFrame: 24 months
measure: Evaluation of the body kinetic profile of intratumorally injected NBTXR3
timeFrame: 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Santa Fe
country: United States
facility: Christus St. Vincent Regional Cancer Center
state: New Mexico
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, School of Medicine
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Bethlehem
country: United States
facility: St Luke's University Health Network
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
Study officials:
affiliation: Nanobiotix
name: Pavel Tyan, MD
role: STUDY_DIRECTOR
References:
citation: Shen C, Frakes J, Niu J, et al 684 NBTXR3 activated by radiotherapy in combination with nivolumab or pembrolizumab in patients with advanced cancers: results from an ongoing dose escalation phase I trial (Study 1100). Journal for ImmunoTherapy of Cancer 2022;10:doi: 10.1136/jitc-2022-SITC2022.0684