Vaccine-Based Immunotherapy Regimen For NSCLC and TNBC

NCT03674827 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: C3621001VBIR-2
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 34

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.

Conditions

Non-Small Cell Lung Cancer; Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (17)

• Maximum Observed Serum Concentration (Cmax) of Sasanlimab

  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

  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

  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

  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

  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

Study Arms (2)

Dose escalation (Part 1)

EXPERIMENTAL

Participants with NSCLC or TNBC were enrolled at escalating dose levels s of the VBIR-2 regimen.

Biological: PF-06936308

Dose Expansion (Part 2)

EXPERIMENTAL

Participants with metastatic NSCLC will be enrolled at the expansion dose level identified during Part 1 of the study.

Biological: PF-06936308

Interventions

PF-06936308 BIOLOGICAL

PF-06936308 components will be administered 4 times per cycle. A cycle is 4 months.

Also known as: Vaccine-based immunotherapy regimen-2 (VBIR-2)

Dose Expansion (Part 2); Dose escalation (Part 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (34)

UCSD Medical Center - Encinitas

Encinitas, California, 92024, United States

Location

UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital)

La Jolla, California, 92037, United States

Location

UC San Diego Perlman Medical Offices

La Jolla, California, 92037, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

UCLA Hematology/Oncology - Parkside

Santa Monica, California, 90404, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

UCSD Medical Center - Vista

Vista, California, 92081, United States

Location

H Lee Moffitt Cancer Center & Research Institute Inc

Tampa, Florida, 33612, United States

Location

The University of Chicago Medical Center, CCD - Investigational Drug Service Pharmacy

Chicago, Illinois, 60637, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Chicago Comprehensive Cancer Center at Silver Cross Hospital

New Lenox, Illinois, 60451, United States

Location

Orland Park - University of Chicago Center for Advanced Care

Orland Park, Illinois, 60462, United States

Location

Horizon Oncology Research, LLC

Lafayette, Indiana, 47905, United States

Location

InnerVision Advanced Medical Imaging

Lafayette, Indiana, 47905, United States

Location

The University of Kansas Cancer Center, Investigational Drug Services

Fairway, Kansas, 66205, United States

Location

The University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Norton Cancer Institute Downtown

Louisville, Kentucky, 40202, United States

Location

Norton Cancer Institute Pharmacy, Downtown Pharmacy

Louisville, Kentucky, 40202, United States

Location

Norton Hospital

Louisville, Kentucky, 40202, United States

Location

Siteman Cancer Center - St. Peters

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center - West County

Creve Coeur, Missouri, 63141, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University Infusion Center Pharmacy

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center - South County

St Louis, Missouri, 63129, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Washington Medical Center - Translational Research Unit (TRU)

Seattle, Washington, 98195, United States

Location

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

This study was terminated on 10 Feb 2021 by the Sponsor. The decision to terminate this study was based on the results of a strategic evaluation of VBIR-2 within the current Sponsor's oncology portfolio. When the decision of study termination was made, participants enrolled in Part 1 who were still on study were to remain on treatment until 31 Aug 2021; Part 2 of the study was never opened.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: September 18, 2018
• Study Start: November 27, 2018
• Primary Completion: September 27, 2021
• Study Completion: September 27, 2021
• Last Updated: August 23, 2024
• Results First Posted: August 23, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (34)