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
February 2023