Study of NEO-201 in Solid Tumors Expansion Cohorts

NCT03476681 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PB-1801
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 2

Brief Summary

The open label, first-in-human, phase 1, dose escalation component in refractory solid tumors has been completed. The Maximum Tolerated Dose and Recommended Phase 2 Dose (RP2D) was determined to be 1.5mg/kg. The Expansion Phase of this study is currently enrolling subjects with non small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), cervical and uterine cancers who progressed on front line therapy. Subjects will be treated with NEO-201 at the RP2D (1.5 mg/kg) every 2 weeks in combination with pembrolizumab, given 1 day after the NEO-201, at 400 mg IV every 6 weeks.

Conditions

Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Cervical Cancer; Uterine Cancer

Keywords

NEO-201; Monoclonal Antibody; Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Cervical Cancer; Uterine Cancer; Pembrolizumab

Outcome Measures

Primary Outcomes (3)

• Determine the safety of the combination of NEO-201 with pembrolizumab the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  To evaluate toxicity a safety lead in of 3 to 6 subjects will be conducted. The safety lead in will be 42 days long, consisting of 3 doses of NEO-201 and 1 dose of pembrolizumab followed by a 2 week assessment. All appropriate treatment areas will have access to a the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site http://ctep.cancer.gov/protocolDevelopment/electronic\_applications/ctc.htm.

  1.5 years

• Determine Objective Response Rate (either Complete Response or Partial Response) as determined by RECIST v1.1 guidelines

  For the purposes of this study, subjects will be re-evaluated for response every 12 weeks. Response will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) \[Eur J Ca 45:228-247, 2009\]. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.

  1.5 years

• Determine Progression Free Survival as determined by RECIST v1.1 guidelines

  For the purposes of this study, subjects will be re-evaluated for progression every 12 weeks. Progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) \[Eur J Ca 45:228-247, 2009\]. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.

  1.5 years

Secondary Outcomes (4)

• Toxicities including treatment emergent adverse events and the character and incidence of Grade 1-4 toxicities.

  1.5 years

• Characterize the area under the concentration-time curve (AUC) of the pharmacokinetics (PK) of NEO-201 combination therapy with pembrolizumab.

  1.5 years

• Characterize Peak Plasma Concentration (Cmax) of the pharmacokinetics (PK) of NEO-201 in combination with pembrolizumab.

  1.5 years

• Characterize the Minimum Plasma Concentration (Cmin) of the pharmacokinetics (PK) of NEO-201 in combination with pembrolizumab.

  1.5 years

Study Arms (1)

NEO-201 in combination with pembrolizumab

EXPERIMENTAL

Subjects will receive 3 doses NEO-201 in combination with one dose of pembrolizumab in a 42 day cycle. This course will be repeated in the absence of disease progression or unacceptable toxicity.

Drug: NEO-201 in combination with pembrolizumab

Interventions

NEO-201 in combination with pembrolizumab DRUG

NEO-201 will be given intravenously every 2 weeks in combination with pembrolizumab. In each cycle subjects will receive 3 doses of NEO 201 and one dose of pembrolizumab.

Also known as: IHC screening for NEO-201 target

NEO-201 in combination with pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: \>/=18 years
• Diagnosis:
• Subjects must have histologically or cytologically confirmed recurrent, locally advanced unresectable or metastatic cancer confirmed by the Laboratory of Pathology, NCI
• Subjects enrolled in the expansion cohorts must have advanced non-small cell lung cancer, HNSCC, uterine cancer, or cervical cancer that has progressed during or after at least one front-line standard of care treatment, including chemotherapy and/or targeted therapy
• Tumor is positive for NEO-201 antigen expression (defined as at least 10% of tumor cells expressing NEO-201 target antigen).
• Patient is not a candidate for potentially curative surgery or radiation.
• Tumor has the additional characteristics described below for the disease specific expansion cohorts:
• NSCLC:
• Tumor(s) must express PD-L1 (TSP \> 1%) as determined by an FDA-approved test and/or is microsatellite instability-high (MSI-H) or mismatch repair deficient, and/or is tumor mutational burden-high (TMB-H) \[≥10 mutations/megabase (mut/Mb)\], as determined by an FDA-approved test.
• Patients with EGFR, ALK1, ROS1 or BRAF V600E genomic tumor aberrations must have had disease progression on FDA-approved agents for these aberrations.
• Patients without these genomic tumor aberrations must have received immune-checkpoint inhibitor previously, either as a single agent or in combination with chemotherapy.
• Cervical Cancer:
• Tumor(s) express a combined positive score (CPS) \> 1, as determined by an FDA approved test and/or is microsatellite instability-high (MSI-H) or mismatch repair deficient, and/or is tumor mutational burden-high (TMB-H) \[≥10 mutations/megabase (mut/Mb)\], as determined by an FDA-approved test
• HNSCC • Patients are allowed to have received pembrolizumab previously, either alone or as part of a multiagent regimen.
• Uterine carcinoma

You may not qualify if:

• History of disseminated or uncontrolled brain metastases or central nervous system disease. Brain metastases will be considered controlled if SD on two consecutive brain MRIs, performed at least 2 months apart, and subject is without seizures.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to NEO-201 or other agents used in this study.
• Any major surgery within 14 days of enrollment.
• Receiving any other investigational agents.
• No archival tissue available and a lesion(s) that cannot be safely biopsied via percutaneous route, or is unwilling to undergo biopsy.
• Has an uncontrolled concomitant illness including, but not limited to, ongoing or active infection, uncontrolled diabetes mellitus, symptomatic congestive heart failure, unstable angina pectoris, hypokalemia, family history of Long QT Syndrome or presence of cardiac arrhythmia.
• Subjects who are assessed to have unacceptable risk of developing infection from neutropenia will be excluded at the Investigator's discretion.
• HIV-positive subjects on combination antiretroviral therapy are ineligible because of the unknown potential for pharmacokinetic interactions with NEO-201. In addition, these subjects are at increased risk of lethal infections which could complicate the toxicity assessment of this study. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated.
• Subject has other serious medical illness, including a second malignancy, or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Pregnant women are excluded from this study because the potential for teratogenic or abortifacient effects due to NEO-201 is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with NEO-201, breastfeeding should be discontinued if the mother is treated with NEO-201.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to start of study therapy.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g.., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Subjects who experienced severe or life-threatening immune-related AEs with prior immune checkpoint therapy requiring medical intervention (steroid or immunosuppressant drugs) and permanent discontinuation of therapy, will be excluded. These include, but not limited to colitis, autoimmune hepatitis, hypophysitis, hyperthyroidism, nephritis, myocarditis, GBS, encephalitis.

Sponsors & Collaborators

• Precision Biologics, Inc: lead

Study Sites (2)

National Cancer Institute

Bethesda, Maryland, 20892, United States

RECRUITING

INOVA Schar Cancer Institute

Fairfax, Virginia, 22031, United States

RECRUITING

Related Publications (1)

• Cole CB, Morelli MP, Fantini M, Miettinen M, Fetsch P, Peer C, Figg WD, Yin T, Houston N, McCoy A, Lipkowitz S, Zimmer A, Lee JM, Pavelova M, Villanueva EN, Trewhitt K, Solarz BB, Fergusson M, Mavroukakis SA, Zaki A, Tsang KY, Arlen PM, Annunziata CM. First-in-human phase 1 clinical trial of anti-core 1 O-glycans targeting monoclonal antibody NEO-201 in treatment-refractory solid tumors. J Exp Clin Cancer Res. 2023 Mar 29;42(1):76. doi: 10.1186/s13046-023-02649-6.

  PMID: 36991390 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Uterine Cervical Neoplasms; Uterine Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Kevin Conlon, MD

  National Cancer Institute - Women's Malignancy Branch

  PRINCIPAL INVESTIGATOR

• Azam Ghafoor, MD

  National Cancer Institute - Thoracic and GI Malignancy Branch

  PRINCIPAL INVESTIGATOR

• Charalampos Floudas, MD

  National Cancer Institute - Head and Neck/GUMB

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ann McCoy, RN

CONTACT

240-760-6021; ann.mccoy@nih.gov

Erica Redmond, BSN,RN

CONTACT

240-858-3783; erica.redmond@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In the dose expansion phase subjects with non small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), cervical and uterine cancers will be treated with NEO-201 at 1.5 mg/kg every 2 weeks in combination with pembrolizumab at 400 mg IV every 6 weeks. In each cycle the combination will be given sequentially with NEO-201 on Day 1, followed by pembrolizumab on Day 2 to reduce the risk of additive infusion reactions. NEO-201 will be administered IV every 2 weeks on Days 1, 15 and 29 of a 42-day cycle. Response assessment will be done at the end of Cycle 2 Day 84.

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 26, 2018
• Study Start: January 18, 2019
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): January 15, 2029
• Last Updated: April 24, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)