Clinical trial NCT04181788: Sasanlimab (PF-06801591, PD-1 Inhibitor) in Participants With Advanced Malignancies
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Malignancies
Non-small-cell Lung Cancer
Keywords: Advanced solid tumors
NSCLC
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-11-29
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: 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
measure: Phase 2: AUCτ of PF-06801591 at Steady State
timeFrame: 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
measure: Phase 2: Ctrough of PF-06801591 at Steady State, at Week 12
timeFrame: 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 outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: 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).
measure: Number of Participants With Laboratory Abnormalities
timeFrame: 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).
measure: Pharmacokinetic Parameters: AUCτ After First Dose
timeFrame: 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
measure: Pharmacokinetic Parameters: Ctrough After First Dose
timeFrame: Phase 1b/2: Cycle 2 Day 1 for all Arms
measure: Pharmacokinetic Parameters: Ctrough at Steady State
timeFrame: 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
measure: Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) /Neutralizing Antibodies (NAb)
timeFrame: 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
measure: Number of Participants With Objective Response (OR)
timeFrame: Phase 1b/2: Up to 30 months
measure: Time to Response (TTR)
timeFrame: Phase 1b/2: Up to 30 months
measure: Number of Participants With Objective Response (Complete Response + Partial Response) Reported by Baseline Programmed Death-Ligand 1 (PD-L1) Status (High, Low, and Unknown)
timeFrame: Phase 1b/2: Baseline up to 30 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
state: Shanghai
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei Univ. Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Pushkin
country: Russian Federation
facility: Private Medical Institution "Euromedservice"
state: Saint-petersburg
city: Pyatigorsk
country: Russian Federation
facility: Klinika UZI 4D, LLC
state: Stavropol Region
city: Yaroslavl
country: Russian Federation
facility: State budgetary institution of healthcare of Yaroslavl region "Clinical oncology hospital"
state: Yaroslavskaya Oblast'
city: Chelyabinsk
country: Russian Federation
facility: Evimed Llc
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
city: Kaliningrad
country: Russian Federation
facility: Ars Medika Center, LLC
city: Kaliningrad
country: Russian Federation
facility: GBUZ Regional Clinical Hospital of Kaliningrad region
city: Kopeysk
country: Russian Federation
facility: Enlimed Llc
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncological Dispensary
city: Pesochny
country: Russian Federation
facility: Russian Scientific Center For Radiology and Surgical Technologies
city: Saint-Petersburg
country: Russian Federation
facility: Road clinical clinic of JSC "RZD"
city: Saint-Petersburg
country: Russian Federation
facility: Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg
city: Samara
country: Russian Federation
facility: Medical University REAVIZ
city: Samara
country: Russian Federation
facility: Medical University REAVIZ
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Pliuty Village
country: Ukraine
facility: Limited Liability Company "MedX-ray International Group"
state: KIEV Region
city: Khodosivka
country: Ukraine
facility: Asklepion Medical Center
state: Kyivska Oblast
city: Sumy
country: Ukraine
facility: "Medeya Sumy" LLC
state: SUMY Region
city: Dnipro
country: Ukraine
facility: Communal Non-profit Enterprise City Clinical Hospital #4 of Dnipro City Council
city: Dnipro
country: Ukraine
facility: LLC "AR DI PI Ukraine"
city: Ivano-Frankivsk
country: Ukraine
facility: Municipal Non-profit Enterprise "SubCarpathian Clinical Oncological Centre of Ivano-Frankivsk RC"
city: Kirovohrad
country: Ukraine
facility: Private Enterprise of Private Manufacturing Company "Acinus", Medical and Diagnostic Center
city: Kyiv
country: Ukraine
facility: Medical centre "Verum" Limited Liability Company
city: Kyiv
country: Ukraine
facility: Vita Сom LLC
city: Kyiv
country: Ukraine
facility: The State Institution "Romodanov Neurosurgery Institute,
city: Odesa
country: Ukraine
facility: Llc Medical Centre
city: Odesa
country: Ukraine
facility: Municipal Non-profit Enterprise Odesa Regional Clinical Hospital of Odesa Regional Council
city: Odesa
country: Ukraine
facility: Llc Lidermed
city: Sumy
country: Ukraine
facility: Municipal Non Profit enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Center"
city: Uzhgorod
country: Ukraine
facility: Llc Medical Center Diamed
city: Uzhgorod
country: Ukraine
facility: MNPE Central City Clinical Hospital of Uzhhorod City Council
city: Zhytomyr
country: Ukraine
facility: Мunicipal non-profit enterprise "Zhytomyr Regional Oncology Dispensary" of Zhytomyr Regional Council
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: