Clinical trial NCT05741242: A Phase 1b/2, Multi-center, Single Arm Study to Assess the Safety and Efficacy of Neoantigen Synthetic Long Peptide Vaccines in Patients With Local Or Metastatic Solid Tumors
Official title: A Phase 1b/2, Multi-center, Single Arm Study to Assess the Safety and Efficacy of Neoantigen Synthetic Long Peptide Vaccines in Patients With Local Or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
PHASE2
Conditions: Cancer
Solid Tumor
Keywords: personalized neoantigen vaccine
Lead sponsor: Jaime Leandro Foundation for Therapeutic Cancer Vaccines
Sponsor class: OTHER
First posted: 2023-02-23
Enrollment: 136
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase 1b/2, Multi-center, Single Arm Study to Assess the Safety and Efficacy of Neoantigen Synthetic Long Peptide Vaccines in Patients With Local Or Metastatic Solid Tumors

Detailed description: This is a Simon-two stage multi-cohort study to assess the safety and efficacy of neoantigen synthetic long peptide vaccines in patients with local or metastatic solid tumors.

1. To assess the efficacy of NeoSLP vaccination by investigator assessment of Progression-Free Survival at 12 months (PFS12).
2. To assess efficacy of NeoSLP vaccination by assessment of Time to Treatment Failure (TTF).
3. To assess efficacy of NeoSLP vaccination by assessment of Overall Survival at 24 months (OS24).
4. To investigate the immunogenicity of NeoSLP vaccines by ELISpot assay. 5. To assess the safety and tolerability of NeoSLP vaccines.

Eligibility criteria: Patients must satisfy the following criteria to be enrolled in the protocol:

Main Inclusion Criterion:

Pancreatic

1. Patients who have local or metastatic pancreatic adenocarcinoma and have started first line therapy of Folfirinox (physician's choice for any concomitant therapies)
2. Patients who have undergone somatic tumor sequencing should consider FDA-approved pan-solid tumor therapies if they harbor an FDA-approved somatic alteration. For example, Entrectinib or Larotrectinib (if NTRK gene fusion- positive), Selpercatinib (if RET gene fusion-positive), Pembrolizumab (if MSI-H, dMMR, or TMB-H\[≥10 mut/Mb\]), and PARP inhibitors (BRCA mutations).

Glioblastoma

1. Patients who are within 6 months of diagnosis and have detectable disease as determined by investigator assessment at the start of vaccine administration.

Basket

1. Patients with local or metastatic malignancies, limited treatment options, and an estimated 5-year survival of less than 50% are eligible for enrollment in this cohort.

Other Inclusion Criteria:

1. \>= 12 years of age.
2. ECOG performance status ≤ 2 or Karnofsky score of \>=70.
3. Adequate organ function allowing favorable benefit to risk ratio per the treating physician
4. Systemic corticosteroid therapy is permitted provided dosing is no greater than 4 mg per day (dexamethasone or equivalent) on the day of vaccine administration.
5. Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

1. History of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty or known allergy to a component of the neoantigen synthetic long peptide vaccine.
2. Intercurrent illness requiring chronic use of medications that may interfere with rescue medications for treatment of vaccine-related anaphylaxis or attenuate immune response to vaccine treatment (immunosuppressive therapies).
3. Psychiatric illness or social situations that would limit compliance with study requirements.
4. History of pre-existing immunodeficiency disorder or autoimmune condition requiring immunosuppressive therapy that would preclude response to vaccine.
5. Females of childbearing potential may participate provided they agree to practice abstinence; and, if heterosexually active, agree to use at least 2 highly effective contraceptive methods throughout the study and for 3 months following the last dose of study drug; and have a negative serum pregnancy test.
6. Females of non-childbearing potential must be post-menopausal or have been surgically sterilized.
7. Male subjects with a female partner of childbearing potential must agree to practice abstinence or to use a physician-approved contraceptive method throughout the study and for 3 months following the last dose of study drug.

Primary outcomes:
measure: To assess the efficacy of NeoSLP vaccination by investigator assessment of Progression-Free Survival at 12 months (PFS12).
timeFrame: Until progression or death, assessed up to 12 months post first vaccine administration.
Secondary outcomes:
measure: To assess efficacy of NeoSLP vaccination by assessment of Time to Treatment Failure (TTF).
timeFrame: Assessed up to 12 months post first vaccine administration
measure: To assess efficacy of NeoSLP vaccination by assessment of Overall Survival at 24 months (OS24).
timeFrame: Until death, assessed up to 24 months post first vaccine administration
measure: To assess the safety and tolerability of NeoSLP vaccines.
timeFrame: Assessed up to 60 days from last vaccine administration
Other outcomes:
measure: To investigate the immunogenicity of NeoSLP vaccines by ELISpot assay.
timeFrame: Assessed at baseline before first vaccine administration and day 50 post
Locations:
city: Beverly Hills
country: United States
facility: Precision NextGen Oncology & Research Center
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Bridgeton
country: United States
facility: St. Louis Cancer Care
state: Missouri
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
References: