A Study of PF-07260437 in Advanced or Metastatic Solid Tumors
- Conditions
- Breast NeoplasmsEndometrial NeoplasmsOvarian Neoplasms
- Interventions
- Diagnostic Test: B7-H4 IHC
- Registration Number
- NCT05067972
- Lead Sponsor
- Pfizer
- Brief Summary
A study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-07260437, a B7-H4 x CD3 bispecific mAb, in participants aged ≥18 years of age with advanced or metastatic breast cancer, ovarian cancer or endometrial cancer. Adult participants with other advanced or metastatic high B7-H4 expressing tumors may be considered after discussion with and approval from sponsor.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 30
- Part 1: Histological/cytological diagnosis of selected locally advanced or metastatic breast cancer, endometrial cancer and ovarian cancer
- Part 2A:In second line or more, participants with histological/cytological diagnosis of locally advanced or metastatic HR+ HER2- breast cancer showing high B7-H4 expression
- Part 2B: In second line or more participants with histological or cytological diagnosis of locally advance or metastatic HR+ Her2- breast cancer or triple negative breast cancer (TNBC) with no biomarker pre-selection
- Part 2C: In second line or more participants with histological diagnosis of locally advance or metastatic triple negative breast cancer with high B7-H4 expression
- Thyroid function within normal laboratory range; in participants with abnormal thyroid function if Free T4 is normal and participant is clinically euthyroid, participants is eligible
- Participants with any active malignancy within 3 years prior to enrollment
- Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
- History of Grade ≥3 immune mediated adverse events (including liver function tests that where considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co stimulatory agents, etc.) and required immunosuppressive therapy within 1 year of treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Monotherapy dose escalation (Part 1) PF-07260437 Participants will receive PF-07260437 Dose Expansion (Part 2A) - Tumor specific Arm A PF-07260437 Participants will receive PF-07260437 Dose Expansion (Part 2A) - Tumor specific Arm A B7-H4 IHC Participants will receive PF-07260437 Dose Expansion (Part 2B) - Tumor specific Arm B PF-07260437 Participants will receive PF-07260437 Dose Expansion (Part 2B) - Tumor specific Arm B B7-H4 IHC Participants will receive PF-07260437 Dose Expansion (Part 2C) - Tumor specific Arm C B7-H4 IHC Participants will receive PF07260437 Dose Expansion (Part 2C) - Tumor specific Arm C PF-07260437 Participants will receive PF07260437
- Primary Outcome Measures
Name Time Method Number of Participants With Dose-Limiting Toxicities (DLTs) in Dose Escalation - Part 1 The first dose of the study intervention (C1D1) through Day 28 for participants without a priming dose or through Day 42 for participants with a priming dose. Any of the following treatment-related adverse events (AEs) occurring during the DLT observation period were classified as DLTs: Hematological DLTs: neutropenia Grade (G) 4, febrile neutropenia, ≥G3 for \>7d (days), G3 with infection; thrombocytopenia G4, G3 with bleeding or requiring platelet transfusion; anemia G4, G3 requiring blood transfusion. Non-hematologic: hepatic toxicity; ≥G3 fatigue for ≥5d, ≥G3 nausea/vomiting or diarrhea for ≥3d, ≥G3 cytokine release syndrome (CRS) of any duration/QTcF prolongation/anaphylaxis, G5 AE without clear reason; immune-related (ir)AE: ≥G4 irAEs/colitis, G3/4 non-infectious pneumonitis, G2 pneumonitis not resolved to ≤G1 within 3d of the initiation of max supportive care. Severity of AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of CRS, which were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading for CRS.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) - Part 1 Baseline (Day 1 of dosing ) through 4 week follow-up, up to 35.1 weeks An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was defined as any AE that occurred from first dose of study intervention to either last dose of study treatment + 90 days, start of new anti-cancer therapy, or completion in study as determined by disposition, whichever was earliest. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, or was a congenital anomaly/birth defect. AEs were graded by the investigator according to CTCAE v5.0.
Number of Participants With Clinically Significant Laboratory Abnormalities - Part 1 Baseline through up to 35.1 weeks Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test \[for all female participants\]) and urine (urine pregnancy test \[for all female participants\]). Clinical significance of laboratory parameters was determined at the investigator's discretion.
- Secondary Outcome Measures
Name Time Method Single Dose: Time to Maximal Plasma Concentration (Tmax) Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1 Time to maximal plasma concentration following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.
Number of Participants With Immune-Related Adverse Events (irAEs) Day 1 up to 90 days after the last dose of study intervention (Day 246 [C9D15]), up to approximately 336 days irAEs included gastrointestinal (ie, diarrhea/colitis), dermatological (ie, rash), pulmonary (ie, pneumonitis), hepatic (ie, liver test elevation), renal (ie, creatinine increased), cardiac (ie, myocarditis), endocrine (ie, endocrine disorder), and other toxicities.
Number of Participants by Categories of Anti-Drug Antibody (ADA) Against PF-07260437 On Day 1 of Cycle 1, 2, 3. From Cycle 4 onwards: collection on Day 1 of every 3 cycles (C4D1, C7D1, etc.) until end-of-treatment visit, up to 35.1 weeks. Number of participants with positive ADA against PF-07257876 were summarized for each treatment arm. A participant had treatment-induced ADA response if he/she had negative or missing ADA at baseline and ≥1 post-treatment ADA positive titer. A participant had treatment-boosted ADA response if he/she had positive titer at baseline and a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample.
Single Dose: Maximal Concentration (Cmax) Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1 Maximum observed serum concentration following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.
Single Dose: Area Under the Curve (AUCtau) Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1 Area under the plasma concentration-time profile from time 0 to time tau (τ), the dosing interval following single dose of PF-07260437. The multiple dose PK samples were not collected due to dose interruption or discontinuation. The PK sampling schedule was designed to evaluate the dosing interval of 2 weeks. Since the 100/300/800 group received the second dose (300 ug) only 1 week after the first dose. The PK parameters were not calculable.
Trial Locations
- Locations (15)
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
University of Washington Medical Center - Mountlake
🇺🇸Seattle, Washington, United States
Pan American Center for Oncology Trials- Hospital Oncologico
🇵🇷Rio Piedras, Puerto Rico
Swedish Cancer Institute Edmonds Campus
🇺🇸Edmonds, Washington, United States
Pan American Center for Oncology Trials, LLC
🇵🇷Rio Piedras, Puerto Rico
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Moffitt Cancer Center at McKinley Campus
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
🇺🇸Duarte, California, United States
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
🇺🇸New Lenox, Illinois, United States
The University of Chicago Medicine Center of Advanced Care Orland Park
🇺🇸Orland Park, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Pan American Center for Oncology Trials
🇵🇷Rio Piedras, Puerto Rico
Montefiore Einstein Center for Cancer Care
🇺🇸Bronx, New York, United States