Clinical trial NCT03674827: Vaccine-Based Immunotherapy Regimen For NSCLC and TNBC
Official title: A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES AND TREATMENT INTENSIFICATION OF A VACCINE-BASED IMMUNOTHERAPY REGIMEN-2 (VBIR-2) (PF-06936308) FOR ADVANCED NON-SMALL CELL LUNG CANCER AND METASTATIC TRIPLE-NEGATIVE BREAST CANCER
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Triple-negative Breast Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-09-18
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Part 1of the study will evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of increasing doses of a vaccine-based immunotherapy regimen (VBIR-2) for patients with advanced or metastatic non-small cell lung cancer and metastatic triple-negative breast cancer.

Part 2 will evaluate the safety, pharmacokinetics and pharmacodynamics, immunogenicity and preliminary evidence of efficacy of the Expansion dose of VBIR-2 in participants with advanced or metastatic non-small cell lung cancer.

Detailed description: The study is divided into two parts, Dose Escalation (Part 1) in participants with NSCLC and TNBC without acceptable alternative treatment options, followed by Dose Expansion (Part 2) in participants with NSCLC who have progressed on or after treatment with platinum-based chemotherapy and treatment with 1 immune checkpoint inhibitor, given concurrently or sequentially with chemotherapy.

Part 1 has been completed.

Eligibility criteria: Inclusion Criteria:

Part 1:Histological or cytological diagnosis of non-small cell lung cancer or triple-negative breast cancer. Adequate bone marrow, renal and liver function.

Part 2: Histological or cytological diagnosis of metastatic non-small cell lung cancer previously treated with 1 or 2 regimens in metastatic setting including a CPI and platinum-based chemotherapy. Adequate bone marrow, renal and liver function.

Exclusion Criteria:

* Known symptomatic brain metastases
* ECOG performance status greater than or equal to 2
* Concurrent immunotherapy
* History of or active autoimmune disorders (including but not limited to: myasthenia gravis, thyroiditis, pneumonitis, rheumatoid arthritis, multiple sclerosis, systemic lupus, erythematosus, scleroderma) and other conditions that disorganize or alter the immune system.
* History of inflammatory bowel disease.
* Current use of any implanted electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.
* Presence of any surgical or traumatic metal implants at the site of administration

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 6 months after End of Treatment (EOT; 22 months in maximum)
measure: Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3)
timeFrame: Baseline up to 6 months after EOT (22 months in maximum)
measure: Number of Participants With AEs Leading to Discontinuation or Dose Reduction
timeFrame: Baseline up to 6 months after EOT (22 months in maximum)
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: The first 28 days following the first AdC68 vaccination (Cycle 1 Day 1)
measure: Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4)
timeFrame: Baseline up to 6 months after EOT (22 months in maximum)
measure: Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4)
timeFrame: Baseline up to 6 months after EOT (22 months in maximum)
measure: Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4)
timeFrame: Baseline up to 6 months after EOT (22 months in maximum)
measure: Proportion of Participants Who Achieved Complete Response, Partial Response or Stable Disease for More Than 6 Months Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria (Part 2)
timeFrame: Performed every 8 weeks from baseline up to Week 32
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Sasanlimab
timeFrame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4, and 6 after EOT visit
measure: Cmax of Tremelimumab
timeFrame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
measure: Time to Maximum Concentration (Tmax) of Sasanlimab
timeFrame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
measure: Tmax of Tremelimumab
timeFrame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
measure: Area Under the Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sasanlimab
timeFrame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
measure: AUCinf of Tremelimumab
timeFrame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
measure: Trough Concentrations After Multiple Dosing (Ctrough) of Sasanlimab
timeFrame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; Months 2, 4, 6 after EOT visit
measure: Ctrough of Tremelimumab
timeFrame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1
measure: Objective Response Rate (ORR) Using RECIST v1.1
timeFrame: Performed every 8 weeks from baseline up to Week 32
measure: Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC
timeFrame: Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable).
measure: PFS Using RECIST v1.1 With TNBC
timeFrame: Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable).
measure: Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab
timeFrame: Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing.
measure: Number of Participants With Neutralizing Antibody (NAb) Against Sasanlimab
timeFrame: Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing.
measure: Number of Participants With ADA Against Tremelimumab
timeFrame: Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
measure: Number of Participants With NAb Against Tremelimumab
timeFrame: Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
measure: Titers of Treatment-Induced ADA and NAb Against Sasanlimab
timeFrame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing.
measure: Titers of Treatment-Induced ADA and NAb Against Tremelimumab
timeFrame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: UCSD Medical Center - Encinitas
state: California
city: La Jolla
country: United States
facility: UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital)
state: California
city: La Jolla
country: United States
facility: UC San Diego Perlman Medical Offices
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center - Hillcrest
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Parkside
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Vista
country: United States
facility: UCSD Medical Center - Vista
state: California
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center & Research Institute Inc
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center, CCD - Investigational Drug Service Pharmacy
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: New Lenox
country: United States
facility: University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
state: Illinois
city: Orland Park
country: United States
facility: Orland Park - University of Chicago Center for Advanced Care
state: Illinois
city: Lafayette
country: United States
facility: Horizon Oncology Research, LLC
state: Indiana
city: Lafayette
country: United States
facility: InnerVision Advanced Medical Imaging
state: Indiana
city: Fairway
country: United States
facility: The University of Kansas Cancer Center, Investigational Drug Services
state: Kansas
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute Downtown
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute Pharmacy, Downtown Pharmacy
state: Kentucky
city: Louisville
country: United States
facility: Norton Hospital
state: Kentucky
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Infusion Center Pharmacy
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St. Peters
state: Missouri
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: University of Washington Medical Center - Translational Research Unit (TRU)
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: