Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
B8011007
- SECONDARY ID:
2019-003818-14
- NCT ID:
NCT04181788
Conditions
- Advanced Malignancies
- Non-small-cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
PF-06801591 | | Arm A1 (Phase 1b) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A1 (Phase 1b) | Experimental | | |
Arm B1 (Phase 1b) | Experimental | | |
Arm A2 (Phase 2) | Experimental | | |
Arm B2 (Phase 2) | Experimental | | |
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase 1b: Number of participants with Dose-Limiting Toxicities (DLT) |
Time Frame: | At the end of cycle 1 (28 days) for Arm A1 and (42 days) for Arm B1 |
Safety Issue: | |
Description: | A DLT is any of a predefined set of unacceptable adverse events that are observed and that are related to the investigational agent. |
Secondary Outcome Measures
Measure: | Number of participants with Treatment-Emergent Adverse Events |
Time Frame: | Baseline and up to 90 days post treatment period |
Safety Issue: | |
Description: | Assessment of the overall safety and tolerability. |
Measure: | Number of participants with laboratory abnormalities |
Time Frame: | Baseline and up to 30 days post treatment period |
Safety Issue: | |
Description: | Assessment of the overall safety and tolerability. |
Measure: | Pharmacokinetic parameters: AUC after first dose |
Time Frame: | Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months) |
Safety Issue: | |
Description: | AUC is defined as the area under the curve after the first dose. |
Measure: | Pharmacokinetic parameters: Ctrough after first dose |
Time Frame: | Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months) |
Safety Issue: | |
Description: | Ctrough after first dose is defined as the concentration at the end of the first dosing interval of PF-06801591. |
Measure: | Pharmacokinetic parameters: Ctrough at steady State |
Time Frame: | Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months) |
Safety Issue: | |
Description: | Ctrough at steady state is defined as the concentration at the end of PF-06801591 dosage interval at steady state. |
Measure: | Anti-Drug Antibody (ADA) levels of PF-06801591/Neutralizing antibodies titers for PF-06801591 |
Time Frame: | Arm A1 and Arm A2 (each cycle is 28 days): On day 1 of cycles 1, 2, 3, 4, 6, 8, 10 and EOT (up to 24 months). Arm B1 and Arm B2 (each cycle is 42 days): On day 1 of cycles 1, 2, 3, 4, 5, 7 and EOT (up to 24 months) |
Safety Issue: | |
Description: | Immunogenicity assessment of PF-06801591. |
Measure: | Number of participants with Objective Response |
Time Frame: | Every 12 weeks (up to 24 months) |
Safety Issue: | |
Description: | Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 from the date of first dose of study treatment (Phase 1b) or randomization (Phase 2) until the date of the first documentation of progression of disease. |
Measure: | Time to Response (TTR) |
Time Frame: | Every 12 weeks (up to 24 months) |
Safety Issue: | |
Description: | TTR is the time from first dose of study treatment (Phase 1b) or randomization (Phase 2) to the date of first documentation of objective tumor response (CR or PR) by RECIST 1.1 that is subsequently confirmed. |
Measure: | PD-L1 expression in baseline |
Time Frame: | Baseline |
Safety Issue: | |
Description: | Correlation(s) between PD-L1 expression in baseline tumor tissue and pharmacodynamic markers and/or clinical activity. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Pfizer |
Trial Keywords
- Advanced solid tumors
- NSCLC
Last Updated
August 18, 2021