NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD-1 Therapy
- Conditions
- RadiotherapyImmunotherapyMicrosatellite Instability-High Solid Malignant TumourMetastasis from Malignant Tumor of LiverSquamous Cell Carcinoma of Head and NeckMetastasis from Malignant Tumor of CervixMetastasis from Malignant Melanoma of Skin (disorder)Metastatic Triple-Negative Breast CarcinomaMetastatic NSCLCMetastatic Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT03589339
- Lead Sponsor
- Nanobiotix
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 145
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description NBTXR3 activated by SABR followed by anti-PD-1 monotherapy Nivolumab Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab NBTXR3 activated by SABR followed by anti-PD-1 monotherapy SABR Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab NBTXR3 activated by SABR followed by anti-PD-1 monotherapy Pembrolizumab Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab NBTXR3 activated by SABR followed by anti-PD-1 monotherapy NBTXR3 Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab
- Primary Outcome Measures
Name Time Method [Dose Escalation Part]: Determination of the Recommended Dose 24 Months Determination of DLTs, the MTD (if possible), and RP2Ds for each cohort
[Dose Expansion Part]: Safety Evaluation at RP2D 24 Months Incidence of Grade 3 and higher treatment-related AEs
- Secondary Outcome Measures
Name Time Method Evaluation of the anti-tumor response of R3/RT/PD-1 24 months Evaluation of the Objective Response Rate: complete or partial response, as defined by RECIST 1.1 and iRECIST
Evaluation of the body kinetic profile of intratumorally injected NBTXR3 24 months Evaluation of the time-course dependent accumulation of hafnium in blood and urine following NBTXR3 intratumoral injection
Assessment of the safety and feasibility of R3/RT/PD-1 24 months Assessment of the number of participants with related late onset toxicities defined as any Grade ≥3 AE occurring after the EOT visit and determination of the number of participants with feasible NBTXR3 intratumoral injection
Trial Locations
- Locations (13)
Christus St. Vincent Regional Cancer Center
🇺🇸Santa Fe, New Mexico, United States
St Luke's University Health Network
🇺🇸Bethlehem, Pennsylvania, United States
Sanford Cancer Center
🇺🇸Sioux Falls, South Dakota, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Henry Ford Cancer Institute
🇺🇸Detroit, Michigan, United States
Northwell Health
🇺🇸Manhasset, New York, United States
University of North Carolina, School of Medicine
🇺🇸Chapel Hill, North Carolina, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States