NCT05061537 · REGISTRY CONDITION SEARCH

Study of PF-07263689 in Participants With Selected Advanced Solid Tumors

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2024-04-12

This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and expansion study intended to evaluate the safety, viral load kinetics and shedding, pharmacodynamic, and anti-tumor activity of PF-07263689, either alone or in combination with sasanlimab (an investigational anti-programmed cell death protein 1 \[PD-1\] antibody), in patients with selected locally advanced or metastatic solid tumors who have exhausted all available standard of care therapies available to them. The study consists of 2 parts: Part 1 dose escalation for PF-07263689 monotherapy (Part 1A) and in combination with sasanlimab (Part 1B), followed by Part 2 dose expansion for the combination therapy.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

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outcome · POSTED

Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment Related Treatment Emergent Adverse Events and Treatment Related Serious Adverse Events

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outcome · POSTED

Part 1: Number of Participants With Treatment Emergent Adverse Events Based on Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Grade

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outcome · POSTED

Part 1: Number of Participants With Hematology Abnormalities by Maximum On-Treatment CTCAE Grade

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outcome · POSTED

Part 1: Number of Participants With Clinical Chemistry Abnormalities by Maximum On-Treatment CTCAE Grade

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outcome · POSTED

Part 2: Number of Participants With Treatment Emergent Adverse Events, Serious Adverse Events, Treatment Related Treatment Emergent Adverse Events and Treatment Related Serious Adverse Events

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outcome · POSTED

Part 2: Number of Participants With Treatment Emergent Adverse Events Based on Maximum CTCAE Version 5 Grade

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outcome · POSTED

Part 2: Number of Participants With Laboratory Abnormalities by Maximum On-Treatment CTCAE Grade

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outcome · POSTED

Part 2: Objective Response Rate

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outcome · POSTED

Part 1: Objective Response Rate

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outcome · POSTED

Part 1: Duration of Response

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outcome · POSTED

Part 1: Progression Free Survival

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outcome · POSTED

Part 1: Time to Progression

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outcome · POSTED

Part 1: Maximum Observed Concentration (Cmax) of PF-07263689 in Blood

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outcome · POSTED

Part 1: Time to Maximum Concentration (Tmax) of PF-07263689 in Blood

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outcome · POSTED

Part 1: Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration of PF-07263689 in Blood

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outcome · POSTED

Part 1b: Trough Concentration of Sasanlimab

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outcome · POSTED

Part 1: Viral Titers in Saliva, Urine and Skin Swabs During 30, 45 and 60 Days After the Last PF-07263689 Dose

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outcome · POSTED

Part 1: Percentage of Participants With Positive Neutralizing Antibodies Against PF-07263689 and Sasanlimab

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outcome · POSTED

Part 1: Percentage of Participants With Positive Anti-interleukin 2 Antibodies

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outcome · POSTED

Part 2: Maximum Observed Concentration (Cmax) of PF-7263689 in Blood

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outcome · POSTED

Part 2: Time to Maximum Concentration (Tmax) of PF-07263689 in Blood

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outcome · POSTED

Part 2: Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration of PF-07263689 in Blood

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outcome · POSTED

Part 2: Trough Concentration of Sasanlimab

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outcome · POSTED

Part 2: Viral Titers in Saliva, Urine and Skin Swabs During 30, 45 and 60 Days After the Last PF-07263689 Dose

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outcome · POSTED

Part 2: Percentage of Participants With Positive Anti-drug Antibodies Against PF-07263689 and Sasanlimab

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outcome · POSTED

Part 2: Titer for Anti-PF-07263689 Antibody

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outcome · POSTED

Part 2: Percentage of Participants With Positive Anti-interleukin 2 Antibodies

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outcome · POSTED

Part 2: Titer for Anti-IL2 Antibodies

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outcome · POSTED

Part 2: Disease Control Rate

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outcome · POSTED

Part 2: Duration of Response

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outcome · POSTED

Part 2: Progression Free Survival

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outcome · POSTED

Part 2: Time to Progression

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outcome · POSTED

Part 2: Overall Survival

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Histological or cytological diagnosis of locally advanced or metastatic solid tumors known to have approved therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor agents * Have exhausted (or refuse) all available standard of care therapy (e.g., including anti-PD1/programmed death ligand 1 \[PDL1\] if applicable) or for whom no standard therapy is available for their tumor type * Patients with prior anti-PD1/PDL1 must have documentation of primary or secondary resistance to last prior anti-PD1/PDL1 therapy according to Immunotherapy Resistance Committee (SITC) (Kluger et al, 2020) * Have at least 1 measurable lesion by RECIST 1.1 that has not been previously irradiated (for Part 2 only) * Have recently obtained archival tumor tissue sample available, or undergo de novo tumor biopsy * Eastern Cooperative Oncology Group (ECOG) PS 0-1 * Adequate hematologic, renal, and liver functions * Dose Escalation (Part 1A and 1B): Any advanced or metastatic solid tumor fulfilling other relevant eligibility criteria. * Dose Expansion (Part 2): Tumor specific cohorts (NSCLC, RCC, melanoma, MSS CRC) must have received prior approved therapies (Part 2) Exclusion Criteria: * Other active malignancy * Recent major surgery * Systemic anticancer therapy and chemotherapy within protocol-defined washout period * Known or suspected hypersensitivity to prior treatment with any vaccinia oncolytic, pox virus, or antiviral agents within the past 10 years * Current or history of myocarditis or congestive heart failure (New York Heart Association \[NYHA\] III-IV); unstable angina; or serious uncontrolled arrhythmia or recent myocardial infarction * Active or history of interstitial lung disease (ILD)/pneumonitis * Patients requiring chronic systemic immunosuppressants * History of severe immune mediated side effect that was considered related to prior immune modulatory therapy and requiring immunosuppressive therapy * Known symptomatic brain metastases requiring steroids * History of or ongoing severe inflammatory skin conditions or severe eczema having required medical treatment * Any prior or planned organ transplant * Presence of any open, active wound requiring treatment
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants will receive PF-07263689 once a week for 4 doses
intervention Names
Biological: PF-07263689
label
Monotherapy dose escalation (Part 1A)
type
EXPERIMENTAL
description
Participants will receive PF-07263689 intravenous (IV) once week for 4 doses in combination with sasanlimab subcutaneous (SC) once every 4 weeks
intervention Names
Biological: PF-07263689
Biological: Sasanlimab
label
Combination dose escalation (Part 1B)
type
EXPERIMENTAL
description
Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks
intervention Names
Biological: PF-07263689
Biological: Sasanlimab
label
Dose expansion (Part 2) - Tumor specific Arm A
type
EXPERIMENTAL
description
Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks
intervention Names
Biological: PF-07263689
Biological: Sasanlimab
label
Dose expansion (Part 2) - Tumor specific Arm B
type
EXPERIMENTAL
description
Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks
intervention Names
Biological: PF-07263689
Biological: Sasanlimab
label
Dose expansion (Part 2) - Tumor specific Arm C
type
EXPERIMENTAL

interventions

arm Group Labels
Combination dose escalation (Part 1B)
Dose expansion (Part 2) - Tumor specific Arm A
Dose expansion (Part 2) - Tumor specific Arm B
Dose expansion (Part 2) - Tumor specific Arm C
Monotherapy dose escalation (Part 1A)
description
Genetically engineered oncolytic vaccinia virus
name
PF-07263689
type
BIOLOGICAL
arm Group Labels
Combination dose escalation (Part 1B)
Dose expansion (Part 2) - Tumor specific Arm A
Dose expansion (Part 2) - Tumor specific Arm B
Dose expansion (Part 2) - Tumor specific Arm C
description
A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/ PD-L2
name
Sasanlimab
type
BIOLOGICAL

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 13
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
DLTs=occurrence of any of following adverse events (AEs) attributable to PF-07263689 in first cycle (cycle=28 days): Hematologic: grade(G)4 neutropenia lasting \>5 days; febrile neutropenia; G3 neutropenia with infection, thrombocytopenia with bleeding; G4 thrombocytopenia. Non-hematologic: any treatment-related G\>=3 toxicity; clinical events consistent with Hy's law; any G3 cytokine release syndrome (CRS) not improving to G\<=2 within 72 hours despite medical management; any G4 CRC; G\>=3 toxicity of any duration affecting vital organs; G4 vaccinia infection lasting \>=6 days; G\>=3 toxicities persisting for \>3 days despite medical therapy (e.g. nausea, vomiting, diarrhea, fatigue); G \>=3 rash not resolving to G\<2 within 21 days with supportive measures; G\>=3 lab abnormalities not controlled to G \<=2 with or without appropriate medical management within 3 days; treatment-related AE inducing a delay by 2 weeks in receiving next scheduled dose; clinically important or persistent toxicities.
measure
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
time Frame
Up to 28 days
description
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that at any dose met 1 or more of the following criteria: resulted in death, was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; an important medical event; required inpatient hospitalization or prolongation of existing hospitalization. TEAE was defined as any adverse event that occurred during the on-treatment period, on or after the first dose of study treatment. Relatedness was based on investigator's assessment.
measure
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment Related Treatment Emergent Adverse Events and Treatment Related Serious Adverse Events
time Frame
From first dose of study treatment until 90 days after last dose of study treatment or before start of new anti-cancer therapy (up to maximum of 10.45 months)
description
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE was defined as any AE that occurred during the on-treatment period, on or after the first dose of study treatment. AEs were graded using CTCAE version 5 where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening; urgent intervention indicated; and grade 5= death related to AE.
measure
Part 1: Number of Participants With Treatment Emergent Adverse Events Based on Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Grade
time Frame
From first dose of study treatment until 90 days after last dose of study treatment or before start of new anti-cancer therapy (up to maximum of 10.45 months)
description
Hematology abnormalities were graded using CTCAE version 5 where, grade 0=non-missing lab value outside the grading range for the corresponding lab parameter; grade 1=mild; grade 2=moderate; grade 3=severe; grade 4= life-threatening. Only those categories with non-zero values for any of the arms have been reported.
measure
Part 1: Number of Participants With Hematology Abnormalities by Maximum On-Treatment CTCAE Grade
time Frame
From first dose of study treatment until 1 month follow-up (28+/-7) days after last dose of study treatment (up to 24 days of treatment exposure)
description
Clinical chemistry abnormalities were graded using CTCAE version 5 where, grade 0=non-missing lab value outside the grading range for the corresponding lab parameter; grade 1=mild; grade 2=moderate; grade 3=severe; grade 4= life-threatening. Only those categories with non-zero values for any of the arms have been reported.
measure
Part 1: Number of Participants With Clinical Chemistry Abnormalities by Maximum On-Treatment CTCAE Grade
time Frame
From first dose of study treatment until 1 month follow-up (28+/-7) days after last dose of study treatment (up to 24 days of treatment exposure)
description
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that at any dose met 1 or more of the following criteria: resulted in death, was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; an important medical event; required inpatient hospitalization or prolongation of existing hospitalization. TEAE was defined as any adverse event that occurred during the on-treatment period, on or after the first dose of study treatment. Relatedness was planned to be assessed by investigator.
measure
Part 2: Number of Participants With Treatment Emergent Adverse Events, Serious Adverse Events, Treatment Related Treatment Emergent Adverse Events and Treatment Related Serious Adverse Events
time Frame
From first dose of study treatment until 90 days after last dose of study treatment or before start of new anti-cancer therapy (up to 2 years)
description
AEs were planned to be graded using CTCAE version 5 where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening; urgent intervention indicated; and grade 5= death related to AE.
measure
Part 2: Number of Participants With Treatment Emergent Adverse Events Based on Maximum CTCAE Version 5 Grade
time Frame
From first dose of study treatment until 90 days after last dose of study treatment or before start of new anti-cancer therapy (up to 2 years)
description
Hematology and clinical chemistry parameters were planned to be assessed.
measure
Part 2: Number of Participants With Laboratory Abnormalities by Maximum On-Treatment CTCAE Grade
time Frame
From first dose of study treatment until 35 days after last dose of study treatment or before start of new anti-cancer therapy (up to 2 years)
description
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) and was determined using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 millimeter \[mm\] short axis), PR: at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.
measure
Part 2: Objective Response Rate
time Frame
From first dose of study treatment until CR or PR (up to 2 years)

secondary Outcomes

description
ORR was defined as the percentage of participants with a best overall response of CR or PR and was determined using RECIST version 1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. 95% confidence interval (CI) was based on Clopper-Pearson method.
measure
Part 1: Objective Response Rate
time Frame
From first dose of study treatment until CR or PR (up to maximum follow-up of 10.45 months)
description
Duration of response was defined as the time from first documentation of CR or PR to date of first documentation of progressive disease (PD) or death due to any cause. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non- pathological in size (\<10 mm short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. PD: 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions.
measure
Part 1: Duration of Response
time Frame
From first documentation of CR or PR to date of first documentation of PD or death due to any cause (up to maximum follow-up of 10.45 months)
description
Progression free survival was defined as time from start date of treatment to the date of first documentation of PD or death due to any cause. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions. 95% CI was based on Brookmeyer and Crowley method.
measure
Part 1: Progression Free Survival
time Frame
From start date of treatment to the date of first documentation of PD or death due to any cause (up to maximum follow-up of 10.45 months)
description
Time to progression was defined as the time from start date of treatment to the date of the first documentation of PD. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm and unequivocal progression of pre-existing lesions. 95% CI was based on Brookmeyer and Crowley method.
measure
Part 1: Time to Progression
time Frame
From start date of treatment to the date of first documentation of PD (up to maximum follow-up of 10.45 months)
measure
Part 1: Maximum Observed Concentration (Cmax) of PF-07263689 in Blood
time Frame
Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
measure
Part 1: Time to Maximum Concentration (Tmax) of PF-07263689 in Blood
time Frame
Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
measure
Part 1: Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration of PF-07263689 in Blood
time Frame
Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)
measure
Part 1b: Trough Concentration of Sasanlimab
time Frame
pre-dose on Day 1, 8, 15 and 22
description
Viral titers in each matrix (saliva, urine and skin swabs \[30 days post last dose only\]) at 30, 45 and 60 days after last dose of study treatment is reported in this outcome measure.
measure
Part 1: Viral Titers in Saliva, Urine and Skin Swabs During 30, 45 and 60 Days After the Last PF-07263689 Dose
time Frame
At 30, 45 and 60 days post last dose of study treatment (up to 24 days of treatment exposure)
description
A participant was considered NAb positive if (1) baseline titer was missing or negative and participant had \>= 1 post-treatment positive titer (treatment-induced) or (2) positive titer at baseline and had a ratio of \>= 4 in titer (dilution) to baseline in \>= 1 post-treatment sample (treatment-boosted). Percentage of participants with positive neutralizing antibodies against PF-07263689 is presented in this outcome measure. Data was not collected for sasanlimab as no participants were enrolled in Part 1b of the study.
measure
Part 1: Percentage of Participants With Positive Neutralizing Antibodies Against PF-07263689 and Sasanlimab
time Frame
From Baseline (pre-dose) on Day 1 up to Day 22
description
A participant was considered anti-drug antibody (ADA) positive if (1) baseline titer was missing or negative and participant had \>= 1 post-treatment positive titer (treatment-induced) or (2) positive titer at baseline and had a ratio of \>= 4 in titer (dilution) to baseline in \>= 1 post-treatment sample (treatment-boosted). Percentage of participants with positive anti-interleukin 2 antibodies against PF-07263689 is presented in this outcome measure.
measure
Part 1: Percentage of Participants With Positive Anti-interleukin 2 Antibodies
time Frame
From Baseline (pre-dose) on Day 1 up to Day 22
measure
Part 2: Maximum Observed Concentration (Cmax) of PF-7263689 in Blood
time Frame
Day 1 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 2, Day 3, Day 4, Day 8 (pre-dose, 0.5, 1, 4, 8 hours post-dose), Day 9, Day 10, Day 15 and 22 (pre-dose and 4 hours post-dose)

Full study description

brief Summary: This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and expansion study intended to evaluate the safety, viral load kinetics and shedding, pharmacodynamic, and anti-tumor activity of PF-07263689, either alone or in combination with sasanlimab (an investigational anti-programmed cell death protein 1 \[PD-1\] antibody), in patients with selected locally advanced or metastatic solid tumors who have exhausted all available standard of care therapies available to them. The study consists of 2 parts: Part 1 dose escalation for PF-07263689 monotherapy (Part 1A) and in combination with sasanlimab (Part 1B), followed by Part 2 dose expansion for the combination therapy.

Source references