CLINICAL TRIAL / NCT03589339
NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy
- Interventional
- Recruiting
- NCT03589339
Contact Information
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
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.
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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
- Immunotherapy
- Immunotherapy
- Radiotherapy
- Renal Cancer