RECRUITING

Study of NEO-201 in Solid Tumors Expansion Cohorts

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase 1/2 With Expansion Cohorts in a Study of NEO-201 in Adults With Chemo-Resistant Solid Tumors

Quick Facts

Study Start:2019-01-18

Study Completion:2026-10-15

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03476681

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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(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. * Must have archived tissue (10 unstained slides or tissue block), or must have tumor which can be safely biopsied percutaneously and be willing to undergo a tumor biopsy * MEASURABLE/EVALUABLE DISEASE: Measurable disease (by RECISTv1.1) * INFORMED CONSENT: Voluntary written informed consent before performance of any study-related procedure that is not part of normal medical care * PERFORMANCE STATUS: ECOG ≤ 2; or Karnofsky performance status of ≥ 50% * LABORATORY FUNCTION: * Screening laboratory data within 21 days of the first dose of study drug. Subject must have adequate organ function: * Hemoglobin \> 9 g/dL, or on stable doses (hematocrit stable within 1 gram and dose stable for one month) of erythropoietin or similar medication * Absolute neutrophil count (ANC) ≥1,500/mm3 * Platelets ≥ 100,000/mm3 * Total bilirubin ≤ 2.0 mg/dL * ALT and AST ≤ 3 times the ULN, or, if the subject has liver metastases, ≤ 5 times the ULN * Creatinine ≤ 1.5 mg/dL or creatinine clearance \> 40 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal, as calculated by the Cockcroft Gault formula * PRIOR THERAPY: * At least 14 days must have elapsed since treatment with oral tyrosine kinase inhibitors, or until toxicities associated with TKI therapy have resolved * At least 21 days must have elapsed since treatment with previous monoclonal antibodies, or until toxicities associated with mAb therapy have resolved * At least 4 weeks must have elapsed since any chemotherapeutic agents at the time of enrollment (or 6 weeks for regimens containing BCNU or mitomycin C) * At least 2 weeks must have elapsed since any systemic corticosteroids at the time of enrollment * Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines. * XRT: At least 7 days after local palliative XRT (small port) * Subjects must have recovered from any acute toxicity related to prior therapy, except for alopecia. Toxicity should be ≤ grade 1, or ≤ grade 2 for peripheral neuropathy, or hypothyroidism * Subject is expected to be able to remain on a study protocol for at least 8 weeks * BIRTH CONTROL: Female subject is post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study, and 2 weeks after completion of NEO-201 administration or 4 months after the last dose of pembrolizumab (according to package labeling), whichever is later.	* 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.

Inclusion Criteria

Exclusion Criteria

* 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(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.
* Must have archived tissue (10 unstained slides or tissue block), or must have tumor which can be safely biopsied percutaneously and be willing to undergo a tumor biopsy
* MEASURABLE/EVALUABLE DISEASE: Measurable disease (by RECISTv1.1)
* INFORMED CONSENT: Voluntary written informed consent before performance of any study-related procedure that is not part of normal medical care
* PERFORMANCE STATUS: ECOG ≤ 2; or Karnofsky performance status of ≥ 50%
* LABORATORY FUNCTION:
* Screening laboratory data within 21 days of the first dose of study drug. Subject must have adequate organ function:
* Hemoglobin \> 9 g/dL, or on stable doses (hematocrit stable within 1 gram and dose stable for one month) of erythropoietin or similar medication
* Absolute neutrophil count (ANC) ≥1,500/mm3
* Platelets ≥ 100,000/mm3
* Total bilirubin ≤ 2.0 mg/dL
* ALT and AST ≤ 3 times the ULN, or, if the subject has liver metastases, ≤ 5 times the ULN
* Creatinine ≤ 1.5 mg/dL or creatinine clearance \> 40 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal, as calculated by the Cockcroft Gault formula
* PRIOR THERAPY:
* At least 14 days must have elapsed since treatment with oral tyrosine kinase inhibitors, or until toxicities associated with TKI therapy have resolved
* At least 21 days must have elapsed since treatment with previous monoclonal antibodies, or until toxicities associated with mAb therapy have resolved
* At least 4 weeks must have elapsed since any chemotherapeutic agents at the time of enrollment (or 6 weeks for regimens containing BCNU or mitomycin C)
* At least 2 weeks must have elapsed since any systemic corticosteroids at the time of enrollment
* Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
* XRT: At least 7 days after local palliative XRT (small port)
* Subjects must have recovered from any acute toxicity related to prior therapy, except for alopecia. Toxicity should be ≤ grade 1, or ≤ grade 2 for peripheral neuropathy, or hypothyroidism
* Subject is expected to be able to remain on a study protocol for at least 8 weeks
* BIRTH CONTROL: Female subject is post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study, and 2 weeks after completion of NEO-201 administration or 4 months after the last dose of pembrolizumab (according to package labeling), whichever is later.

* 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.

Contacts and Locations

Study Contact

Ann McCoy, RN

CONTACT

240-760-6021

ann.mccoy@nih.gov

Erica Redmond, BSN,RN

CONTACT

240-858-3783

erica.redmond@nih.gov

Principal Investigator

Kevin Conlon, MD

PRINCIPAL_INVESTIGATOR

National Cancer Institute - Women's Malignancy Branch

Azam Ghafoor, MD

PRINCIPAL_INVESTIGATOR

National Cancer Institute - Thoracic and GI Malignancy Branch

Charalampos Floudas, MD

PRINCIPAL_INVESTIGATOR

National Cancer Institute - Head and Neck/GUMB

Study Locations (Sites)

National Cancer Institute

Bethesda, Maryland, 20892

United States

INOVA Schar Cancer Institute

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Precision Biologics, Inc

Kevin Conlon, MD, PRINCIPAL_INVESTIGATOR, National Cancer Institute - Women's Malignancy Branch
Azam Ghafoor, MD, PRINCIPAL_INVESTIGATOR, National Cancer Institute - Thoracic and GI Malignancy Branch
Charalampos Floudas, MD, PRINCIPAL_INVESTIGATOR, National Cancer Institute - Head and Neck/GUMB

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-01-18

Study Completion Date2026-10-15

Study Record Updates

Study Start Date2019-01-18

Study Completion Date2026-10-15

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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