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

• ClinicalTrials.gov Identifier: NCT03589339
• Recruitment Status: Recruiting
• First Posted: July 17, 2018
• Last Update Posted: March 22, 2024
• Sponsor: Nanobiotix
• Information provided by (Responsible Party): Nanobiotix

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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)	Drug: NBTXR3; Radiation: SABR; Drug: Nivolumab; Drug: Pembrolizumab	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 145 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 16, 2019
• Estimated Primary Completion Date: April 30, 2027
• Estimated Study Completion Date: May 30, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: NBTXR3 activated by SABR followed by anti-PD-1 monotherapy; Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab	Drug: NBTXR3; Single intra Tumoral injection; Radiation: SABR; Radiotherapy given as a definite number of fractions at the dose defined for each radiation field; Other Names: Stereotaxic Ablative Radiotherapy; Stereotaxic Body Radiation Therapy; Drug: Nivolumab; Anti-PD-1 monotherapy; Other Name: Opdivo; Drug: Pembrolizumab; Anti-PD-1 monotherapy; Other Name: Keytruda

Outcome Measures

Primary Outcome Measures :

1. [Dose Escalation Part]: Determination of the Recommended Dose [ Time Frame: 24 Months ]
   Determination of DLTs, the MTD (if possible), and RP2Ds for each cohort
2. [Dose Expansion Part]: Safety Evaluation at RP2D [ Time Frame: 24 Months ]
   Incidence of Grade 3 and higher treatment-related AEs

Secondary Outcome Measures :

1. Evaluation of the anti-tumor response of R3/RT/PD-1 [ Time Frame: 24 months ]
   Evaluation of the Objective Response Rate: complete or partial response, as defined by RECIST 1.1 and iRECIST
2. Assessment of the safety and feasibility of R3/RT/PD-1 [ Time Frame: 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
3. Evaluation of the body kinetic profile of intratumorally injected NBTXR3 [ Time Frame: 24 months ]
   Evaluation of the time-course dependent accumulation of hafnium in blood and urine following NBTXR3 intratumoral injection

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Pavel Tyan, MD; +49 176 81319375; pavel.tyan@nanobiotix.com

Locations

United States, California

University of California San Francisco; Recruiting

San Francisco, California, United States, 94158

Contact: Jason Chan, MD

United States, Florida

Moffitt Cancer Center; Recruiting

Tampa, Florida, United States, 33612

Contact: George Yang, MD

United States, Georgia

Emory University; Recruiting

Atlanta, Georgia, United States, 30308

Contact: William Stokes, MD

United States, Illinois

University of Chicago Medical Center; Recruiting

Chicago, Illinois, United States, 60637

Contact: Ari Rosenberg, MD

United States, Maryland

Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center; Active, not recruiting

Baltimore, Maryland, United States, 21287

United States, Michigan

Karmanos Cancer Institute; Recruiting

Detroit, Michigan, United States, 48201

Contact: Ammar Sukari, MD

Henry Ford Cancer Institute; Active, not recruiting

Detroit, Michigan, United States, 48202

United States, New Mexico

Christus St. Vincent Regional Cancer Center; Recruiting

Santa Fe, New Mexico, United States, 87505

Contact: Andrea Teague, MD

United States, New York

Northwell Health; Recruiting

Manhasset, New York, United States, 11030

Contact: Bhupesh Parashar, MD

United States, North Carolina

University of North Carolina, School of Medicine; Recruiting

Chapel Hill, North Carolina, United States, 27516

Contact: Colette Shen, MD, PhD

United States, Ohio

Gabrail Cancer Center; Recruiting

Canton, Ohio, United States, 44718

Contact: Nashat Gabrail, MD

United States, Pennsylvania

St Luke's University Health Network; Recruiting

Bethlehem, Pennsylvania, United States, 18015

Contact: William Smith, MD

United States, South Dakota

Sanford Cancer Center; Recruiting

Sioux Falls, South Dakota, United States, 57104

Contact: Michele Lohr, MD

Sponsors and Collaborators

Nanobiotix

Investigators

• Study Director: Pavel Tyan, MD; Nanobiotix

More Information

Publications:

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

• Responsible Party: Nanobiotix
• ClinicalTrials.gov Identifier: NCT03589339
• Other Study ID Numbers: 1100
• First Posted: July 17, 2018
• Last Update Posted: March 22, 2024
• Last Verified: March 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nanobiotix:

Oral Cavity Cancer; Oropharynx Cancer; Lung Metastasis; Liver Metastasis

Additional relevant MeSH terms:

Carcinoma; Neoplasms; Melanoma; Neoplasm Metastasis; Neoplasms, Second Primary; Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Melanoma, Cutaneous Malignant; Liver Neoplasms; Uterine Cervical Neoplasms; Urinary Bladder Neoplasms; Microsatellite Instability; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Carcinoma, Squamous Cell; Neoplastic Processes; Pathologic Processes; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases