NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy
Hematopoietic Malignancies
Melanoma
18 Years and older, Male and Female
1100 (primary)
NCI-2019-03108
NBTXR3-1100
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.
Objectives
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
- 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
Treatment Sites in Georgia
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