Vaccine-Based Immunotherapy Regimen For NSCLC and TNBC

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer; Triple-negative Breast Cancer
• Intervention / Treatment: Biological: PF-06936308

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Encinitas, California, United States, 92024
      • UCSD Medical Center - Encinitas
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • La Jolla, California, United States, 92037
      • UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital)
    • La Jolla, California, United States, 92037
      • UC San Diego Perlman Medical Offices
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center - Hillcrest
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology - Parkside
    • Vista, California, United States, 92081
      • UCSD Medical Center - Vista
  • Florida
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center & Research Institute Inc
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago Medical Center
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center, CCD - Investigational Drug Service Pharmacy
    • New Lenox, Illinois, United States, 60451
      • University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
    • Orland Park, Illinois, United States, 60462
      • Orland Park - University of Chicago Center for Advanced Care
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research, LLC
    • Lafayette, Indiana, United States, 47905
      • InnerVision Advanced Medical Imaging
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Clinical Research Center
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Cancer Center, Investigational Drug Services
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute Downtown
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute Pharmacy, Downtown Pharmacy
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center - West County
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center - South County
    • Saint Louis, Missouri, United States, 63110
      • Washington University Infusion Center Pharmacy
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center - St. Peters
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah, Huntsman Cancer Institute
    • Salt Lake City, Utah, United States, 84112
      • University of Utah, Huntsman Cancer Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Translational Research Unit (TRU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation (Part 1); Participants with NSCLC or TNBC were enrolled at escalating dose levels s of the VBIR-2 regimen.	Biological: PF-06936308; PF-06936308 components will be administered 4 times per cycle. A cycle is 4 months.; Other Names: Vaccine-based immunotherapy regimen-2 (VBIR-2)
Experimental: Dose Expansion (Part 2); Participants with metastatic NSCLC will be enrolled at the expansion dose level identified during Part 1 of the study.	Biological: PF-06936308; PF-06936308 components will be administered 4 times per cycle. A cycle is 4 months.; Other Names: Vaccine-based immunotherapy regimen-2 (VBIR-2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or considered to be an important medical event. AEs included both SAEs and non-serious AEs.	Baseline up to 6 months after End of Treatment (EOT; 22 months in maximum)
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)	An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Grades of AEs were defined by NCI CTCAE v5.0. Grade 1 = asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2 = minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4 = events with life-threatening consequences, urgent intervention indicated; Grade 5 = death related to AE.	Baseline up to 6 months after EOT (22 months in maximum)
Number of Participants With AEs Leading to Discontinuation or Dose Reduction	An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment.	Baseline up to 6 months after EOT (22 months in maximum)
Number of Participants With Dose-Limiting Toxicities (DLTs)	AEs in the first 28 d (days) following the first AdC68 vaccination that were considered possibly related to study treatment and not to disease/progression were DLTs: Grade≥3 neutropenia lasting>7 d, febrile neutropenia, Grade≥3 neutropenic infection, Grade≥3 thrombocytopenia with Grade≥2 clinically significant bleeding, Grade≥3 anemia lasting >7 d, Grade≥3 lymphopenia lasting>14 d; Grade≥3 lab abnormalities associated with symptoms or worsening of an existing condition or that suggested a new disease process or that required additional active management, Grade≥3 AEs considered non-hematologic, non-hepatic major organ toxicity, Grade 3 flu-like symptoms lasting>3 d, fever of >40.0 degree Celsius lasting>3 d, concurrent aspartate aminotransferase or alanine aminotransferase >3x upper limit of normal (ULN) and total bilirubin >2x ULN (potential Hy's law case). Other clinically important or persistent toxicities at discretion of investigator and Pfizer.	The first 28 days following the first AdC68 vaccination (Cycle 1 Day 1)
Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4)	Laboratory abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Hematology parameters included hemoglobin, platelets, white blood cell (WBC) count, neutrophils, eosinophils, monocytes, basophils and lymphocytes. Coagulation should include prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (APTT).	Baseline up to 6 months after EOT (22 months in maximum)
Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4)	Chemistry abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Chemistry parameters included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, total chloride, total calcium, total bilirubin, blood urea nitrogen (or urea), creatinine, uric acid, glucose (nonfasted), albumin, phosphorous or phosphate, lactate dehydrogenase, lipase, amylase, bicarbonate or carbon dioxide, total protein, TSH (reflex free T4 and free T3).	Baseline up to 6 months after EOT (22 months in maximum)
Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4)	Urinalysis abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Urine parameters included urine protein and urine blood.	Baseline up to 6 months after EOT (22 months in maximum)
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)	Clinical Benefit Rate (CBR) is defined as the proportion of participants who achieved anti-tumor responses of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for >6 months. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). All target lesions must be assessed. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. All target lesions must be assessed. SD: Does not qualify for CR, PR or Progression. SD can follow PR only in the rare case that the sum increases by <20% from the nadir, but enough that a previously documented 30% decrease no longer holds.	Performed every 8 weeks from baseline up to Week 32

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of Sasanlimab	Cmax was defined as the maximum observed serum concentration.	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
Cmax of Tremelimumab	Cmax was defined as the maximum observed serum concentration.	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
Time to Maximum Concentration (Tmax) of Sasanlimab	Tmax was defined as the time to reach maximum observed serum concentration.	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
Tmax of Tremelimumab	Tmax was defined as the time to reach maximum observed serum concentration.	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
Area Under the Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sasanlimab	AUCinf was defined as area under the concentration time curve from time 0 extrapolated to infinity. AUCinf of sasanlimab was not reported due to the limited data points during elimination phase, and the lack of a well-characterized terminal phase. A well-characterized terminal phase was defined as one with at least 3 data points, r^2 ≥0.9, and percent of AUCextrap% ≤20%.	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
AUCinf of Tremelimumab	AUCinf was defined as area under the concentration time curve from time 0 extrapolated to infinity. AUCinf of tremelimumab was not reported due to the limited data points during elimination phase, and the lack of a well-characterized terminal phase. A well-characterized terminal phase was defined as one with at least 3 data points, r^2 ≥0.9, and percent of AUCextrap% ≤20%.	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
Trough Concentrations After Multiple Dosing (Ctrough) of Sasanlimab	Ctrough was defined as the drug concentration observed at the last planned timepoint prior to dosing. Ctrough was not calculated for sasanlimab because trough concentration prior to the fifth dose (on Cycle 2 Day 1) were not collected for any participants in Cohorts 4A or 5A.	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
Ctrough of Tremelimumab	Ctrough was defined as the drug concentration observed at the last planned timepoint prior to dosing.	Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1
Objective Response Rate (ORR) Using RECIST v1.1	ORR was defined as the percentage of participants with best overall response based assessment of CR or PR according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). All target lesions must be assessed. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. All target lesions must be assessed.	Performed every 8 weeks from baseline up to Week 32
Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC	PFS was defined as the time from start date to date of first documentation of progression, or death due to any cause. Progression was defined as the appearance of local, regional or distant disease of the same type after complete response or progression of pre-existing lesions.	Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable).
PFS Using RECIST v1.1 With TNBC	PFS was defined as the time from start date to date of first documentation of progression, or death due to any cause. Progression was defined as the appearance of local, regional or distant disease of the same type after complete response or progression of pre existing lesions.	Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable).
Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab	Participants were considered ADA-positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted).	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.
Number of Participants With Neutralizing Antibody (NAb) Against Sasanlimab	A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted). Participants who were either (1) an ADA-negative participant or (2) an ADA-positive participant without treatment-induced or treatment-boosted NAb response were considered as NAb negative.	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.
Number of Participants With ADA Against Tremelimumab	Participants were considered ADA-positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted).	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.
Number of Participants With NAb Against Tremelimumab	A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted). Participants who were either (1) an ADA-negative participant or (2) an ADA-positive participant without treatment-induced or treatment-boosted NAb response were considered as NAb negative. NAb evaluation was not considered as meaningful taken that treatment-induced ADA was found in only 1 participant. Thus, NAb to tremelimumab was not examined.	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.
Titers of Treatment-Induced ADA and NAb Against Sasanlimab	Titers were measured in terms of 1/dilution. Only the samples tested positive for ADA were to be further tested for Nab. Treatment-induced ADA: baseline titer is missing or negative and participant has >= 1 post-treatment positive titer. Treatment-induced NAb: baseline titer was missing or negative and participant had ≥1 post-treatment positive titer.	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.
Titers of Treatment-Induced ADA and NAb Against Tremelimumab	Titers were measured in terms of 1/dilution. Only the samples tested positive for ADA were to be further tested for Nab. Treatment-induced ADA: baseline titer is missing or negative and participant has >= 1 post-treatment positive titer. Treatment-induced NAb: baseline titer was missing or negative and participant had ≥1 post-treatment positive titer. NAb was not examined as the evaluation was not meaningful considering only 1 participant had treatment-induced ADA.	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.

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2018
• Primary Completion (Actual): September 27, 2021
• Study Completion (Actual): September 27, 2021

Study Registration Dates

• First Submitted: August 29, 2018
• First Submitted That Met QC Criteria: September 14, 2018
• First Posted (Actual): September 18, 2018

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Breast Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunomodulating Agents
• Other Study ID Numbers: C3621001; VBIR-2 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No