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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small-cell Lung Cancer; Advanced Malignancies
• Intervention / Treatment: Drug: PF-06801591

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 201107
      • Huashan Hospital Affiliated to Fudan University
• Japan
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Korea, Republic of
  • Incheon, Korea, Republic of, 21656
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei Univ. Health System
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
• Russian Federation
  • Chelyabinsk, Russian Federation, 454048
    • Evimed Llc
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
  • Chelyabinsk, Russian Federation, 454092
    • NUZ "Railway Clinical Hospital at the station Chelyabinsk of JSC "Russian Railways"
  • Kaliningrad, Russian Federation, 236006
    • Ars Medika Center, LLC
  • Kaliningrad, Russian Federation
    • GBUZ Regional Clinical Hospital of Kaliningrad region
  • Kopeysk, Russian Federation, 456620
    • Enlimed Llc
  • Orenburg, Russian Federation, 460021
    • Orenburg Regional Clinical Oncological Dispensary
  • Pesochny, Saint Petersburg, Russian Federation, 197758
    • Russian Scientific Center For Radiology and Surgical Technologies
  • Pyatigorsk, Russian Federation, 357500
    • Magnetic resonance and computer tomography
  • Saint Petersburg, Russian Federation, 195271
    • NS HI "Road Clinical Hospital of JSC "Russian Railways""
  • Saint-Petersburg, Russian Federation, 191119
    • North-West Medical Center
  • Saint-Petersburg, Russian Federation, 192007
    • Road clinical clinic of JSC "RZD"
  • Saint-Petersburg, Russian Federation, 195271
    • Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg
  • Samara, Russian Federation, 443011
    • Medical University REAVIZ
  • Samara, Russian Federation, 443001
    • Medical University REAVIZ
  • St. Petersburg, Russian Federation, 190005
    • LLC Medical Center "Magnit"
  • Chelyabinsk Region
    • Chelyabinsk, Chelyabinsk Region, Russian Federation, 454076
      • SBHI "Chelyabinsk Regional Clinical Hospital"
  • Pesochny
    • Saint Petersburg, Pesochny, Russian Federation, 197758
      • Russian Research Centre for Radiology and Surgical Technologies
  • Saint-petersburg
    • Pushkin, Saint-petersburg, Russian Federation, 196603
      • Private Medical Institution "Euromedservice"
  • Stavropol Region
    • Pyatigorsk, Stavropol Region, Russian Federation, 357502
      • Klinika UZI 4D, LLC
  • Yaroslavskaya Oblast'
    • Yaroslavl, Yaroslavskaya Oblast', Russian Federation, 150054
      • State budgetary institution of healthcare of Yaroslavl region "Clinical oncology hospital"
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• Ukraine
  • Dnipro, Ukraine, 49102
    • Communal Non-profit Enterprise City Clinical Hospital #4 of Dnipro City Council
  • Dnipro, Ukraine, 49102
    • LLC "AR DI PI Ukraine"
  • Dnipro, Ukraine, 49102
    • Llc "Mdc Expert"
  • Ivano-Frankivsk, Ukraine, 76018
    • Municipal Non-profit Enterprise "SubCarpathian Clinical Oncological Centre of Ivano-Frankivsk RC"
  • Kirovohrad, Ukraine, 25006
    • Private Enterprise of Private Manufacturing Company "Acinus", Medical and Diagnostic Center
  • Kropyvnytskyi, Ukraine, 25006
    • Private Enterprise of Private Manufacturing Company "Acinus", Medical and Diagnostic Center
  • Kyiv, Ukraine, 03039
    • Medical centre "Verum" Limited Liability Company
  • Kyiv, Ukraine, 03141
    • Vita Сom LLC
  • Kyiv, Ukraine, 04050
    • SI "Romodanov Neurosurgery Institute National Academy of Medical Sciences of Ukraine"
  • Kyiv, Ukraine, 04050
    • The State Institution "Romodanov Neurosurgery Institute,
  • Odesa, Ukraine, 65006
    • Llc Medical Centre
  • Odesa, Ukraine, 65025
    • Municipal Non-profit Enterprise Odesa Regional Clinical Hospital of Odesa Regional Council
  • Odesa, Ukraine, 65062
    • Llc Lidermed
  • Sumy, Ukraine, 40005
    • Municipal Non Profit enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Center"
  • Uzhgorod, Ukraine, 88000
    • Llc Medical Center Diamed
  • Uzhgorod, Ukraine, 88000
    • MNPE Central City Clinical Hospital of Uzhhorod City Council
  • Zhytomyr, Ukraine, 10002
    • Мunicipal non-profit enterprise "Zhytomyr Regional Oncology Dispensary" of Zhytomyr Regional Cou
  • KIEV Region
    • Pliuty Village, Obuhiv District, KIEV Region, Ukraine
      • Limited Liability Company "MedX-ray International Group"
  • Kyivska Oblast
    • Khodosivka, Kyivska Oblast, Ukraine, 08173
      • Asklepion Medical Center
  • SUMY Region
    • Sumy, SUMY Region, Ukraine, 40021
      • "Medeya Sumy" LLC
  • Sumska Oblast
    • Sumy, Sumska Oblast, Ukraine, 40022
      • Municipal non-profit enterprise of Sumy Regional Council Sumy Regional Clinical Oncology Dispensary

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

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): March 18, 2020
• Primary Completion (Actual): March 3, 2022
• Study Completion (Estimated): January 17, 2025

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 27, 2019
• First Posted (Actual): November 29, 2019

Study Record Updates

• Last Update Posted (Estimated): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Advanced solid tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: B8011007; 2019-003818-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• 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
• product manufactured in and exported from the U.S.: Yes