Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Sarcoma

Carcinoma, Renal Cell

Lung Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urogenital Neoplasms

Urologic Neoplasms

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Kidney Neoplasms

Kidney Diseases

Liver Diseases

Ovarian Cancer

Renal Cell Carcinoma

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Participants will receive PF-07263689 once a week for 4 doses

Participants will receive PF-07263689 intravenous (IV) once week for 4 doses in combination with sasanlimab subcutaneous (SC) once every 4 weeks

Participants will receive PF-07263689 IV once week for 4 doses in combination with sasanlimab SC once every 4 weeks

Genetically engineered oncolytic vaccinia virus

PF-07263689

A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/ PD-L2

Sasanlimab

Pfizer CT.gov Call Center

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.

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

A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY AND PHARMACODYNAMICS OF PF-07263689, EITHER ALONE OR IN COMBINATION WITH AN ANTI-PD-1 ANTIBODY, IN PREVIOUSLY TREATED PARTICIPANTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC SOLID TUMORS

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.

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.

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.

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.

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.

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.

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.

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.

Hematology and clinical chemistry parameters were planned to be assessed.

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.

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.

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.

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.

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.

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.

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.

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.

Disease control rate was the percentage of participants with CR, PR or stable disease (SD), as defined by RECIST 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. SD: Does not qualify for CR, PR, or progression. All target lesions assessed.

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.

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.

Overall survival was defined as the duration from the start of study treatment to the date of death from any cause.

Pfizer

Same event may appear as both non-SAE and a serious AE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Adverse event reported only for Part 1a. Since there was no enrolment for Part 1b and 2, no safety data collected and reported.

Participants with any advanced or metastatic solid tumor indications with approved therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor agents were administered PF-07263689 at a dose 2\*10\^8 plaque forming unit (PFU) once weekly for 4 weeks as an intravenous (IV) push. Participants were followed up for up to 90 days post-last dose of study treatment. Participants were followed up for survival until death, withdrawal of consent, or end of the study.

Part 1A PF-07263689 2*10^8 PFU

Participants with any advanced or metastatic solid tumor indications with approved therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor agents were administered PF-07263689 at a dose 6\*10\^8 PFU once weekly for 4 weeks as an IV push. Participants were followed up for up to 90 days post-last dose of study treatment. Participants were followed up for survival until death, withdrawal of consent, or end of the study.

Part 1A PF-07263689 6*10^8 PFU

Participants with any advanced or metastatic solid tumor indications with approved therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor agents were administered PF-07263689 at a dose 20\*10\^8 PFU once weekly for 4 weeks as an IV push. Participants were followed up for up to 90 days post-last dose of study treatment. Participants were followed up for survival until death, withdrawal of consent, or end of the study.

Part 1A PF-07263689 20*10^8PFU

Participants were planned to receive escalating doses of PF-07263689 in combination with sasanlimab.

Part 1B: PF-07263689 + Sasanlimab

Participants were planned to receive PF-07263689 in combination with sasanlimab at the preliminary combination recommended Phase 2 dose from Part 1B.

Part 2: PF-07263689 + Sasanlimab

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Safety analysis set included all enrolled participants who received at least one dose of study intervention. Data was not collected for Part 1B and Part 2 as no participants were enrolled due to early termination.

Data was not collected for Part 1B and Part 2 as no participants were enrolled due to early termination.

Pfizer ClinicalTrials.gov Call Center

DLT evaluable set included participants who received 3 of the 4 doses of PF-07263689 and had completed the scheduled safety assessments during the DLT observation period or had experienced a DLT. Data is not reported for Part 1b as no participants were enrolled and data was not collected.

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

TEAEs

SAEs

Treatment related TEAEs

Treatment related SAEs

Safety analysis set included all enrolled participants who received at least one dose of study treatment. Data is not reported for Part 1b as no participants were enrolled and data was not collected.

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

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

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

Activated PTT prolonged: Grade 0

Activated PTT prolonged: Grade 1

Activated PTT prolonged: Grade 2

Anemia: Grade 0

Anemia: Grade 1

Anemia: Grade 2

Anemia: Grade 3

Hemoglobin increased: Grade 0

INR increased: Grade 0

INR increased: Grade 1

Leukocytosis: Grade 0

Lymphocyte count decreased: Grade 0

Lymphocyte count decreased: Grade 2

Lymphocyte count decreased: Grade 3

Lymphocyte count increased: Grade 0

Neutrophil count decreased: Grade 0

Neutrophil count decreased: Grade 1

Neutrophil count decreased: Grade 2

Platelet count decreased: Grade 0

Platelet count decreased: Grade 1

White blood cell decreased: Grade 0

White blood cell decreased: Grade 1

White blood cell decreased: Grade 2

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

Alanine aminotransferase increased: Grade 0

Alanine aminotransferase increased: Grade 1

Alkaline phosphatase increased: Grade 0

Alkaline phosphatase increased: Grade 1

Aspartate aminotransferase increased: Grade 0

Aspartate aminotransferase increased: Grade 1

Blood bilirubin increased: Grade 0

Blood bilirubin increased: Grade 1

Creatinine phosphokinase increased: Grade 0

Creatinine phosphokinase increased: Grade 1

Cardiac Troponin I Increased: Grade 0

Cardiac Troponin T Increased: Grade 0

Cardiac Troponin T Increased: Grade 1

Creatinine increased: Grade 0

Creatinine increased: Grade 2

Hypercalcemia: Grade 0

Hyperkalemia: Grade 0

Hyperkalemia: Grade 2

Hypermagnesemia: Grade 0

Hypernatremia: Grade 0

Hypoalbuminemia: Grade 0

Hypoalbuminemia: Grade 1

Hypoalbuminemia: Grade 2

Hypocalcemia: Grade 0

Hypocalcemia: Grade 1

Hypoglycemia: Grade 0

Hypoglycemia: Grade 1

Hypoglycemia: Grade 3

Hypokalemia: Grade 0

Hypokalemia: Grade 2

Hypomagnesemia: Grade 0

Hypomagnesemia: Grade 1

Hyponatremia: Grade 0

Hyponatremia: Grade 1

Hyponatremia: Grade 3

Safety analysis set included all enrolled participants who received at least one dose of study treatment. Data is not reported for Part 1b as no participants were enrolled and data was not collected. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.

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

Data was not collected as no participants were enrolled in Part 2 of the study due to study termination.

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

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

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

Part 2: Objective Response Rate

Response evaluable set included all participants who received at least one dose of study treatment and had baseline disease assessment \[or measurable disease at baseline, if applicable\] and at least one post-baseline disease assessment. Data is not reported for Part 1b as no participants were enrolled and data was not collected.

Part 1: Objective Response Rate

Response evaluable set included all participants who received at least one dose of study treatment and had baseline disease assessment \[or measurable disease at baseline, if applicable\] and at least one post-baseline disease assessment. Only participants with CR or PR were analyzed. Data is not reported for Part 1b as no participants were enrolled and data was not collected.

Part 1: Duration of Response

Full analysis set included all enrolled participants. Data is not reported for Part 1b as no participants were enrolled and data was not collected.

Part 1: Progression Free Survival

Part 1: Time to Progression

Blood viral load Kinetics Analysis Set included all enrolled participants treated who did not have protocol deviations influencing viral load kinetics assessment, and had sufficient information to estimate at least 1 of the parameters of interest. Data is not reported for Part 1b as no participants were enrolled and data was not collected.

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

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

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

Data was not collected as no participants were enrolled in Part 1b of the study due to study termination.

Part 1b: Trough Concentration of Sasanlimab

Saliva; 30 days post last dose

Saliva; 45 days post last dose

Saliva; 60 days post last dose

Skin swab; 30 days post last dose

Urine; 30 days post last dose

Urine; 45 days post last dose

Urine; 60 days post last dose

Vector Shedding Analysis Set included all enrolled participants who were treated and had at least 1 analyte concentration above the lower limit of quantitation. Data is not reported for Part 1b as no participants were enrolled and data was not collected. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure and contributed data to the table and 'Number Analyzed' signifies participants evaluable for the specified time points.

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

Immunogenicity analysis set included all enrolled participants who received at least one dose of study treatment and had at least one sample tested for ADA. Data is not reported for Part 1b as no participants were enrolled and data was not collected.

Spots Global Cancer Trial Database for Study of PF-07263689 in Participants With Selected Advanced Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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