Vaccine-Based Immunotherapy Regimen For NSCLC and TNBC
- Conditions
- Triple-negative Breast CancerNon-Small Cell Lung Cancer
- Interventions
- Biological: PF-06936308
- Registration Number
- NCT03674827
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 36
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion (Part 2) PF-06936308 Participants with metastatic NSCLC will be enrolled at the expansion dose level identified during Part 1 of the study. Dose escalation (Part 1) PF-06936308 Participants with NSCLC or TNBC were enrolled at escalating dose levels s of the VBIR-2 regimen.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to 6 months after End of Treatment (EOT; 22 months in maximum) 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.
Number of Participants With AEs Leading to Discontinuation or Dose Reduction Baseline up to 6 months after EOT (22 months in maximum) 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.
Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) Baseline up to 6 months after EOT (22 months in maximum) 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).
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) Baseline up to 6 months after EOT (22 months in maximum) 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.
Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) Baseline up to 6 months after EOT (22 months in maximum) 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.
Number of Participants With Dose-Limiting Toxicities (DLTs) The first 28 days following the first AdC68 vaccination (Cycle 1 Day 1) 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.
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) Performed every 8 weeks from baseline up to Week 32 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.
Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) Baseline up to 6 months after EOT (22 months in maximum) 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).
- Secondary Outcome Measures
Name Time Method 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 Tmax was defined as the time to reach maximum observed serum concentration.
Trough Concentrations After Multiple Dosing (Ctrough) 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; Months 2, 4, 6 after EOT visit 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.
Ctrough 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 Ctrough was defined as the drug concentration observed at the last planned timepoint prior to dosing.
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 was defined as the maximum observed serum concentration.
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 Cmax was defined as the maximum observed serum concentration.
Number of Participants With ADA Against Tremelimumab 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. 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).
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 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%.
Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab 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. 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).
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 was defined as the time to reach maximum observed serum concentration.
PFS Using RECIST v1.1 With TNBC Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable). 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.
Number of Participants With Neutralizing Antibody (NAb) Against Sasanlimab 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. 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.
AUCinf 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 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%.
Objective Response Rate (ORR) Using RECIST v1.1 Performed every 8 weeks from baseline up to Week 32 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.
Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable). 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.
Titers of Treatment-Induced ADA and NAb Against Tremelimumab 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. 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.
Number of Participants With NAb Against Tremelimumab 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. 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.
Titers of Treatment-Induced ADA and NAb Against Sasanlimab 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 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.
Trial Locations
- Locations (34)
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
University of Utah, Huntsman Cancer Hospital
🇺🇸Salt Lake City, Utah, United States
University of Utah, Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
The University of Kansas Cancer Center, Investigational Drug Services
🇺🇸Fairway, Kansas, United States
The University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
H Lee Moffitt Cancer Center & Research Institute Inc
🇺🇸Tampa, Florida, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
UCSD Medical Center - Encinitas
🇺🇸Encinitas, California, United States
UC San Diego Perlman Medical Offices
🇺🇸La Jolla, California, United States
UCLA Hematology/Oncology
🇺🇸Los Angeles, California, United States
UC San Diego Medical Center - Hillcrest
🇺🇸San Diego, California, United States
UCLA Hematology/Oncology - Santa Monica
🇺🇸Santa Monica, California, United States
UCLA Hematology/Oncology - Parkside
🇺🇸Santa Monica, California, United States
UCSD Medical Center - Vista
🇺🇸Vista, California, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
InnerVision Advanced Medical Imaging
🇺🇸Lafayette, Indiana, United States
The University of Chicago Medical Center, CCD - Investigational Drug Service Pharmacy
🇺🇸Chicago, Illinois, United States
Horizon Oncology Research, LLC
🇺🇸Lafayette, Indiana, United States
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
🇺🇸New Lenox, Illinois, United States
Orland Park - University of Chicago Center for Advanced Care
🇺🇸Orland Park, Illinois, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Washington University Infusion Center Pharmacy
🇺🇸Saint Louis, Missouri, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Washington Medical Center - Translational Research Unit (TRU)
🇺🇸Seattle, Washington, United States
UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Hospital)
🇺🇸La Jolla, California, United States
Siteman Cancer Center - St. Peters
🇺🇸Saint Peters, Missouri, United States
Norton Cancer Institute Downtown
🇺🇸Louisville, Kentucky, United States
Norton Cancer Institute Pharmacy, Downtown Pharmacy
🇺🇸Louisville, Kentucky, United States
Norton Hospital
🇺🇸Louisville, Kentucky, United States