Sasanlimab (PF-06801591, PD-1 Inhibitor) in Participants With Advanced Malignancies

Study Overview
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Brief Summary
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This is a Phase 1b/2 protocol to evaluate pharmacokinetics, safety, efficacy, and pharmacodynamics of PF-06801591, a programmed death-1(PD-1) antagonist monoclonal antibody (mAb) in participants with advanced malignancies. This study consists of 2 parts: Phase 1b part (dose escalation and dose expansion) in patients with advanced malignancies in Asia and a global Phase 2 part in non small cell lung cancer (NSCLC) patients.

Official Title
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A Phase 1b/2 Open-Label Study to Evaluate Pharmacokinetics, Safety, Efficacy, and Pharmacodynamics of PF-06801591 (PD-1 Inhibitor) in Participants With Advanced Malignancies

Conditions
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Advanced Malignancies, Non-small-cell Lung Cancer

Intervention / Treatment
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* Drug: PF-06801591


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years (≥ 20 years in Japan; ≥ 19 years in South Korea) Easter Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate bone marrow function, renal and liver functions Phase 1b Histological or Cytological diagnosis of advanced solid tumor with clinical evidence of response to anti-PD-1 or PD-L1 agent Participant must have received at least 1 prior line of therapy for recurrent or metastatic disease, and must have progressed/relapsed, be refractory, or intolerant to standard therapy approved for the specific tumor type Phase 2 Participants must have a documented diagnosis of stage III where participants are not candidates for surgical resection or definitive chemoradiation, or stage IV NSCLC EGFR mutation, BRAF mutation, and ALK or ROS1 translocation/rearrangement are not permitted Participants whose tumor is known to be PD-L1 positive (Tumor Proportion Score [TPS] ≥1%) or unknown are eligible Up to 1 line of prior therapy in advanced or metastatic disease settings allowed Participant should not have received prior treatment with anti PD-1/PD-L1 drugs At least one measurable lesion as defined by RECIST version 1.1 Exclusion Criteria: Participants with known symptomatic brain metastases requiring steroids Participants with Interstitial Lung Disease history or complication Q-T interval corrected for heart rate QTc > 450 msec for male participants or QTc > 470 msec for female participants or QTc > 480 msec in participants with right bundle branch block. Hypertension that cannot be controlled by medications (eg, systolic > 150 mmHg and diastolic > 90 mmHg) despite optimal medical therapy. Known or suspected hypersensitivity to active ingredient or excipients of the study drug. History of Grade ≥3 immune mediated AE (including AST/ ALT elevations that where considered drug related and cytokine release syndrome [CRS]) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory agents, etc.) and required immunosuppressive therapy (For Phase 1b only). Vaccination with live attenuated vaccines within 4 weeks prior to randomization is prohibited; however inactivated vaccines are permitted.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A1 (Phase 1b)<br> | Drug: PF-06801591<br>* A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.<br>|
| Experimental: Arm B1 (Phase 1b)<br> | Drug: PF-06801591<br>* A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.<br>|
| Experimental: Arm A2 (Phase 2)<br> | Drug: PF-06801591<br>* A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.<br>|
| Experimental: Arm B2 (Phase 2)<br> | Drug: PF-06801591<br>* A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT) | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with first line (1L) and second line (2L) non-small cell lung cancer (NSCLC) (Phase 2). For the Phase 1b, any of the following AEs occurring during the DLT observation period (the first cycle of treatment) which were attributable to the investigational product were classified as DLTs: Grade 5 AE not clearly due to the underlying disease or extraneous causes; Hematologic toxicity; Non-Hematologic Toxicity; Delay of ≥ 3 weeks in receiving the next scheduled administration due to persisting treatment-related toxicities. | Phase 1b: at the end of cycle 1 (28 days) for the PF-06801591 300 mg SC Q4W arms, and (42 days) for the PF-06801591 600 mg SC Q6W arms | 
| Phase 2: AUCτ of PF-06801591 at Steady State | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). AUCτ is area under the plasma concentration-time profile from time zero to the next dose (at steady state, starting at Week 12). (τ = X days, where X = 28 days for Q4W regimen and 42 days for Q6W regimen) | Phase 2: Cycle 4 Day 1, 8, 15, 22 and Cycle 5 Day 1 for the PF-06801591 300 mg SC Q4W arm, and Cycle 3 Day 1, 8, 15, 29 and Cycle 4 Day 1 for the PF-06801591 600 mg SC Q6W arm | 
| Phase 2: Ctrough of PF-06801591 at Steady State, at Week 12 | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). Steady state Ctrough is pre-dose concentration following multiple dosing at steady state (Week 12) | Phase 2: Cycle 4 Day 1 for the PF-06801591 300 mg SC Q4W arm, and Cycle 3 Day 1 for the PF-06801591 600 mg SC Q6W arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Phase 1b/2: On-treatment period is defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day). | 
| Number of Participants With Laboratory Abnormalities | Laboratory results were classified according to the NCI-CTCAE criteria version 5.0. Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care (ADL); Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 1 to Grade 4 laboratory abnormalities were reported. | Phase 1b/2: On-treatment period is defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day). | 
| Pharmacokinetic Parameters: AUCτ After First Dose | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). AUCτ is area under the plasma concentration-time profile from time zero to the next dose (after single dose). (τ = X days, where X = 28 days for Q4W regimen and 42 days for Q6W regimen) | Phase 1b/2: For the PF-06801591 300 mg SC Q4W arms, Cycle 1 Day 1, 8, 15, 22, Cycle 2 Day 1; for the PF-06801591 600 mg SC Q6W arms, Cycle 1 Day 1, 8, 15, 29, Cycle 2 Day 1 | 
| Pharmacokinetic Parameters: Ctrough After First Dose | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). Ctrough is pre-dose concentration after single dose (first dose). | Phase 1b/2: Cycle 2 Day 1 for all Arms | 
| Pharmacokinetic Parameters: Ctrough at Steady State | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). Steady state Ctrough is pre-dose concentration following multiple dosing at steady state (Week 12) | Phase 1b/2: For the PF-06801591 300 mg SC Q4W arms, Day 1 of Cycle 4; for the PF-06801591 600 mg SC Q6W arms, Day 1 of Cycle 3 | 
| Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) /Neutralizing Antibodies (NAb) | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). Treatment-induced ADA = Baseline ADA titer was missing or negative and participant had ≥1 post-treatment positive ADA titer (ADA titer greater than or equal to 99 with assay cut-point of 1.09). Treatment-induced NAb = Baseline NAb titer was missing or negative or ADA-negative and participant had ≥1 post-treatment positive NAb titer. | Phase 1b/2: Day 1 of Cycle 1, 2, 3, 4, 6, 8, 10 and end of treatment (EOT) for the PF-06801591 300 mg SC Q4W arms; Day 1 of Cycle 1, 2, 3, 4, 5, 7 and EOT for the PF-06801591 600 mg SC Q6W arms | 
| Number of Participants With Objective Response (OR) | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). OR was defined as confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1. Complete Response (CR): Complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). All target lesions must be assessed. Partial Response (PR): Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. | Phase 1b/2: Up to 30 months | 
| Time to Response (TTR) | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). TTR was defined for participants with confirmed objective response (CR or PR) as the time from the 'start date' to the date of first documentation of objective tumor response which is subsequently confirmed. | Phase 1b/2: Up to 30 months | 
| Number of Participants With Objective Response (Complete Response + Partial Response) Reported by Baseline Programmed Death-Ligand 1 (PD-L1) Status (High, Low, and Unknown) | This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). OR was defined as confirmed BOR of CR or PR according to RECIST v1.1. CR: Complete disappearance of all target lesions 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: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. All target lesions must be assessed. PD-L1 expression was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest that are defined by tumor cell morphology. | Phase 1b/2: Baseline up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumors, NSCLC