Vaccine-Based Immunotherapy Regimen For NSCLC and TNBC

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of a Vaccine-based Immunotherapy Regimen-2 (VBIR-2) (PF-06936308) for Advanced Non-small Cell Lung Cancer and Metastatic Triple-negative Breast Cancer

Conditions
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Non-Small Cell Lung Cancer, Triple-negative Breast Cancer

Intervention / Treatment
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* Biological: PF-06936308


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate Clinical Benefit Rate (CBR) | Proportion of participants who achieve complete response, partial response or stable disease for more than 6 months at 12, 24 and 36 months using RECIST 1.1. criteria. | Participant will have CT scans/MRI until disease progression for up to 3 years | 
| Incidence and grade of treatment-emergent adverse events including DLTs | DLTs in order to determine the maximum tolerated dose | Baseline up to Day 29 in Cycle 1 (each cycle is 4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tremelimumab and sasanlimab single dose PK parameter (Cmax) | Maximum observed plasma concentration of tremelimumab and sasanlimab (Cmax). | Pre-dose on Day 1, Day 3-6, Day 8, Day 15, Day 22, Day 29, Day 57, Day 85 of Cycle 1 (each cycle is 4 months); pre-dose on Day 1 and Day 29 on Cycle 2; every 5 months thereafter up to Month 22; every 6 months thereafter up to 3 years | 
| Tremelimumab and sasanlimab single dose PK parameter (Tmax) | Time to maximum concentration of tremelimumab and sasanlimab (Tmax) | Pre-dose on Day 1, Day 3-6, Day 8, Day 15, Day 22, Day 29, Day 57, Day 85 of Cycle 1 (each cycle is 4 months); pre-dose on Day 1 and Day 29 on Cycle 2; every 5 months thereafter up to Month 22; every 6 months thereafter up to 3 years | 
| Tremelimumab and sasanlimab single dose PK parameter AUC | Area under the curve from time zero extrapolated to infinity of tremelimumab and sasanlimab | Pre-dose on Day 1, Day 3-6, Day 8, Day 15, Day 22, Day 29, Day 57, Day 85 of Cycle 1 (each cycle is 4 months); pre-dose on Day 1 and Day 29 on Cycle 2; every 5 months thereafter up to Month 22; every 6 months thereafter up to 3 years | 
| Tremelimumab and sasanlimab after multiple doses PK parameter (Ctrough) | Trough concentration after multiple doses of tremelimumab and sasanlimab (Ctrough) | Pre-dose on Day 1, Day 3-6, Day 8, Day 15, Day 22, Day 29, Day 57, Day 85 of Cycle 1 (each cycle is 4 months); pre-dose on Day 1 and Day 29 on Cycle 2; every 5 months thereafter up to Month 22; every 6 months thereafter up to 3 years | 
| Anti drug antibody (ADA) response of tremelimumab and sasanlimab after SC administration with the other components. | Incidence and titers of anti-drug antibodies against tremelimumab and sasanlimab | Day 1, Day 29 and Day 85 on Cycle 1 (each cycle is 4 months); Day 29 on Cycle 2, every 4 months thereafter up to Month 22; every 6 months thereafter up to 3 years | 
| Objective response rate using RECIST 1.1 | Proportion of participants who achieve complete response or partial response. | Participant will have CT scans/MRI at baseline and every 8 weeks until disease progression for up to 3 years | 
| Duration of response using RECIST 1.1 | Median time from first response (complete or partial) until disease progression for up to 3 years in responders. | Participant will have CT scans/MRI at baseline and every 8 weeks until disease progression for up to 3 years | 
| Progression-free survival using RECIST 1.1 | Kaplan-Meier curve for progression up to 3 years. | Participant will have CT scans/MRI at baseline and every 8 weeks until disease progression for up to 3 years |