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

Non-small-cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04181788
• Other study ID #: B8011007
• Secondary ID: 2019-003818-14
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 18, 2020
• Est. completion date: January 17, 2025

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 155
• Est. completion date: January 17, 2025
• Est. primary completion date: March 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Malignancies
• Neoplasms
• Non-small-cell Lung Cancer

Intervention

Drug:
• PF-06801591
A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PDL1/ PD-L2.

Locations

Country	Name	City	State
China	Beijing Cancer hospital	Beijing	Beijing
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei Univ. Health System	Seoul
Russian Federation	Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine	Chelyabinsk
Russian Federation	Evimed Llc	Chelyabinsk
Russian Federation	NUZ "Railway Clinical Hospital at the station Chelyabinsk of JSC "Russian Railways"	Chelyabinsk
Russian Federation	SBHI "Chelyabinsk Regional Clinical Hospital"	Chelyabinsk	Chelyabinsk Region
Russian Federation	Ars Medika Center, LLC	Kaliningrad
Russian Federation	GBUZ Regional Clinical Hospital of Kaliningrad region	Kaliningrad
Russian Federation	Enlimed Llc	Kopeysk
Russian Federation	Orenburg Regional Clinical Oncological Dispensary	Orenburg
Russian Federation	Russian Scientific Center For Radiology and Surgical Technologies	Pesochny, Saint Petersburg
Russian Federation	Private Medical Institution "Euromedservice"	Pushkin	Saint-petersburg
Russian Federation	Klinika UZI 4D, LLC	Pyatigorsk	Stavropol Region
Russian Federation	Magnetic resonance and computer tomography	Pyatigorsk
Russian Federation	NS HI "Road Clinical Hospital of JSC "Russian Railways""	Saint Petersburg
Russian Federation	Russian Research Centre for Radiology and Surgical Technologies	Saint Petersburg	Pesochny
Russian Federation	North-West Medical Center	Saint-Petersburg
Russian Federation	Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg	Saint-Petersburg
Russian Federation	Road clinical clinic of JSC "RZD"	Saint-Petersburg
Russian Federation	Medical University REAVIZ	Samara
Russian Federation	Medical University REAVIZ	Samara
Russian Federation	LLC Medical Center "Magnit"	St. Petersburg
Russian Federation	State budgetary institution of healthcare of Yaroslavl region "Clinical oncology hospital"	Yaroslavl	Yaroslavskaya Oblast'
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taipei Veterans General Hospital	Taipei
Ukraine	Communal Non-profit Enterprise City Clinical Hospital #4 of Dnipro City Council	Dnipro
Ukraine	LLC "AR DI PI Ukraine"	Dnipro
Ukraine	Llc "Mdc Expert"	Dnipro
Ukraine	Municipal Non-profit Enterprise "SubCarpathian Clinical Oncological Centre of Ivano-Frankivsk RC"	Ivano-Frankivsk
Ukraine	Asklepion Medical Center	Khodosivka	Kyivska Oblast
Ukraine	Private Enterprise of Private Manufacturing Company "Acinus", Medical and Diagnostic Center	Kirovohrad
Ukraine	Private Enterprise of Private Manufacturing Company "Acinus", Medical and Diagnostic Center	Kropyvnytskyi
Ukraine	Medical centre "Verum" Limited Liability Company	Kyiv
Ukraine	SI "Romodanov Neurosurgery Institute National Academy of Medical Sciences of Ukraine"	Kyiv
Ukraine	The State Institution "Romodanov Neurosurgery Institute,	Kyiv
Ukraine	Vita ?om LLC	Kyiv
Ukraine	Llc Lidermed	Odesa
Ukraine	Llc Medical Centre	Odesa
Ukraine	Municipal Non-profit Enterprise Odesa Regional Clinical Hospital of Odesa Regional Council	Odesa
Ukraine	Limited Liability Company "MedX-ray International Group"	Pliuty Village, Obuhiv District	KIEV Region
Ukraine	"Medeya Sumy" LLC	Sumy	SUMY Region
Ukraine	Municipal Non Profit enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Center"	Sumy
Ukraine	Municipal Non Profit enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Center"	Sumy
Ukraine	Municipal non-profit enterprise of Sumy Regional Council Sumy Regional Clinical Oncology Dispensary	Sumy	Sumska Oblast
Ukraine	Llc Medical Center Diamed	Uzhgorod
Ukraine	MNPE Central City Clinical Hospital of Uzhhorod City Council	Uzhgorod
Ukraine	?unicipal non-profit enterprise "Zhytomyr Regional Oncology Dispensary" of Zhytomyr Regional Cou	Zhytomyr

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

China,  Japan,  Korea, Republic of,  Russian Federation,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 2: AUCt 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).; AUCt is area under the plasma concentration-time profile from time zero to the next dose (at steady state, starting at Week 12). (t = 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
Primary	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	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).
Secondary	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).
Secondary	Pharmacokinetic Parameters: AUCt After First Dose	This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2).; AUCt is area under the plasma concentration-time profile from time zero to the next dose (after single dose). (t = 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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