QUILT-3.017: Study of NEO-201 in Solid Tumors

Learn more about:
Related Clinical Trial
ctDNA-MRD Based Adjuvant Targeted Therapy for EGFR Positive Stage I Lung Adenocarcinomas Advanced Lung Tumor Treated by Osimertinib Plus Anlotinib Comparative Genomic Profiling of Lung Adenocarcinoma in Asians and Caucasians: A Propensity Matched Analysis Therapeutic ResistAnce and Clonal Evolution of ICIs Distribution and Prognostic Impact of Oncogenic Drivers in Metastatic Lung Adenocarcinoma : a Retrospective Monocentric Study in Nancy University Hospital Center Clinical Study of Camrelizumab Combined With APatinib and Albumin Paclitacxel in Patients With Advanced Lung Adenocarcinoma A Study of IMU-201 (PD1-Vaxx), a B-Cell Immunotherapy, in Adults With Non-Small Cell Lung Cancer Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Icotinib for Completed Resected IB NSCLC With EGFR Mutation Circulating Tumor DNA in Patients at High Risk for Lung Cancer Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer Erlotinib and Radiation Therapy Plus Combination Chemotherapy in Treating Patients With Inoperable Stage III Non-Small Cell Lung Cancer Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Advanced, Metastatic, or Recurrent Non-Small Cell Lung Cancer Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer Phase I IGART Study Using Active Breathing Control and Simultaneous Boost for Patients With NSCLC Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery Bevacizumab, Paclitaxel, Carboplatin, and Radiation Therapy to the Chest in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery QUILT-3.017: Study of NEO-201 in Solid Tumors Photodynamic Therapy in Treating Patients With Lung Cancer Vaccine Treatment for Advanced Non-Small Cell Lung Cancer S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib Single Agent Chemotherapy +/- Nivolumab in Patients With Advanced Squamous or Non-squamous NSCLC With Primary Resistance to Prior PD-1 or PDL-1 Inhibitor Comparison of Different Types of Surgery in Treating Patients With Early-stage Non-small Cell Lung Cancer Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy of NSCLC Patients in China ALK/ROS1/MET Mutations on Plasma ctDNA in Patients With NSCLC The Tracking Molecular Evolution for NSCLC (T-MENC) Study Phase 1a/1b Study of TPST-1495 Alone and With Pembrolizumab in Subjects With Solid Tumors An Integrated Approach to Treating Recurrent Thoracic Carcinomas Resistant to Tyrosine Kinase Inhibitors Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC) P2 of RMT in Combo w Durvalumab or Durva + Chemo in Untreated Adenocarcinoma NSCLC Feasibility and Safety of Nintedanib in Combination With Nivolumab in Pretreated Patients With Advanced or Metastatic NSCLC of Adenocarcinoma Histology Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer Combination Nab-paclitaxel (N-P) and Nintedanib or N-P and Placebo in Relapsed NSCLC Adenocarcinoma Prospective Radiological Study of HRCT to Predict Pathological Noninvasiveness in NSCLC To Compare Efficacy and Safety of CT-P16 and EU-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer Impact of Concomitant Genetic Alterations in EGFR Mutated Adenocarcinoma by NGS Analysis: A Multicenter Study Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With Advanced NSCLC Poziotinib in Stage IV Lung Adenocarcinoma With HER2 Mutation (KASTT001) Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung Lung Cancer Mutation Consortium Protocol The Detection of EGFR Mutations in Liquid Based Cytology Samples NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma A Safety and Efficacy Study of Farletuzumab in Subjects With Adenocarcinoma of the Lung Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03) Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma The Study of Apatinib Plus CIK as the Third Line Therapy for Advanced Lung Adenocarcinoma Patients With Wild-Type EGFR Telomere Biology in Early Adenocarcinoma of the Lung

Brief Title

Study of NEO-201 in Solid Tumors Expansion Cohorts

Official Title

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

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.
    

Detailed Description

      The experimental drug called NEO-201 (the "study drug") is a monoclonal antibody that is
      being tested and is not approved for use in the United States by the FDA.

      As stated above the RP2D was determined at 1.5 mg/kg and in the current Expansion Phase it
      will be administered in combination with pembrolizumab. .

      A safety lead in will be conducted in the first 3 to 6 subjects to evaluate toxicity prior to
      expanding accrual. The safety lead-in will be 42 days in length, consisting of 1 dose of
      pembrolizumab and 3 doses of NEO-201 followed by a 2-week assessment for safety, in subjects
      with any of the expansion cohorts' targeted disease types. The third patient in the safety
      lead in must complete the 30-day assessment (1 dose of pembrolizumab and 3 doses of NEO-201
      followed by a 2-week safety evaluation) and be evaluated for toxicity prior to treating
      additional patients.

      Following completion of the lead-in, expansion cohorts will accrue subjects with NSCLC,
      HNSCC, cervical and uterine cancers who progress on frontline therapy.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

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

Condition

Non Small Cell Lung Cancer

Intervention

NEO-201 in combination with pembrolizumab

Study Arms / Comparison Groups

 NEO-201 in combination with pembrolizumab
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

121

Start Date

January 18, 2019

Completion Date

October 15, 2025

Primary Completion Date

October 15, 2024

Eligibility Criteria

        Inclusion 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 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

        • Patients who are eligible to have received the combination of pembrolizumab plus
        lenvatinib (i.e. patients with tumors that are not MSI or dMMR) must have received this
        regimen, unless considered unsafe due to comorbid conditions (e.g. hypertension,
        proteinuria).

          -  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.

        Should a woman become pregnant or suspect she is pregnant while she or her partner is
        participating in this study, she should inform her treating physician immediately.

        Men treated or enrolled on this protocol must also agree to use adequate contraception
        prior to the study, for the duration of study participation, 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.

        Exclusion Criteria:

          -  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.

        Additional Exclusion Criteria for Expansion Cohorts

        Because patients in the expansion cohort will be receiving pembrolizumab, the following
        additional exclusion criteria apply:

          -  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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Christina M Annunziata, MD,PhD, 240-760-6021, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03476681

Organization ID

PB-1801


Responsible Party

Sponsor

Study Sponsor

Precision Biologics, Inc


Study Sponsor

Christina M Annunziata, MD,PhD, Principal Investigator, National Cancer Institute - Women's Malignancy Branch


Verification Date

October 2021