NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy

Immunotherapy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03589339
• Other study ID #: 1100
• Status: Recruiting
• Phase: Phase 1
• Start date: January 16, 2019
• Est. completion date: May 30, 2028

Study information

• Verified date: March 2024
• Source: Nanobiotix
• Contact: Pavel Tyan, MD
• Phone: +49 176 81319375
• Email: pavel.tyan[@]nanobiotix.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 145
• Est. completion date: May 30, 2028
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Immunotherapy
• Liver Neoplasms
• Melanoma
• Metastasis From Malignant Melanoma of Skin (Disorder)
• Metastasis From Malignant Tumor of Bladder (Disorder)
• Metastasis From Malignant Tumor of Cervix
• Metastatic NSCLC
• Metastatic Renal Cell Carcinoma
• Metastatic Triple-Negative Breast Carcinoma
• Microsatellite Instability
• Microsatellite Instability-High Solid Malignant Tumour
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Second Primary
• Radiotherapy
• Squamous Cell Carcinoma of Head and Neck
• Urinary Bladder Neoplasms
• Uterine Cervical Neoplasms

Intervention

Drug:
• NBTXR3
Single intra Tumoral injection

Radiation:
• SABR
Radiotherapy given as a definite number of fractions at the dose defined for each radiation field

Drug:
• Nivolumab
Anti-PD-1 monotherapy
• Pembrolizumab
Anti-PD-1 monotherapy

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	St Luke's University Health Network	Bethlehem	Pennsylvania
United States	Gabrail Cancer Center	Canton	Ohio
United States	University of North Carolina, School of Medicine	Chapel Hill	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Northwell Health	Manhasset	New York
United States	University of California San Francisco	San Francisco	California
United States	Christus St. Vincent Regional Cancer Center	Santa Fe	New Mexico
United States	Sanford Cancer Center	Sioux Falls	South Dakota
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Nanobiotix

Country where clinical trial is conducted

United States, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[Dose Escalation Part]: Determination of the Recommended Dose	Determination of DLTs, the MTD (if possible), and RP2Ds for each cohort	24 Months
Primary	[Dose Expansion Part]: Safety Evaluation at RP2D	Incidence of Grade 3 and higher treatment-related AEs	24 Months
Secondary	Evaluation of the anti-tumor response of R3/RT/PD-1	Evaluation of the Objective Response Rate: complete or partial response, as defined by RECIST 1.1 and iRECIST	24 months
Secondary	Assessment of the safety and feasibility of R3/RT/PD-1	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	24 months
Secondary	Evaluation of the body kinetic profile of intratumorally injected NBTXR3	Evaluation of the time-course dependent accumulation of hafnium in blood and urine following NBTXR3 intratumoral injection	24 months