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.
Brief Title
A Study of PF-07260437 in Advanced or Metastatic Solid Tumors
Categories
Completion Date
Completion Date Type
Actual
Conditions
Ovarian Neoplasms
Endometrial Neoplasms
Breast Neoplasms
Eligibility Criteria
Inclusion Criteria:
* 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
Exclusion Criteria:
* 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.
* 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
Exclusion Criteria:
* 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.
Inclusion Criteria
Inclusion Criteria:
* 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
* 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
Gender
All
Gender Based
false
Keywords
Cancer of Endometrium
Cancer of the Endometrium
Carcinoma of Endometrium
Endometrial Cancer
Endometrial Carcinoma
Endometrium Cancer
Neoplasms, Endometrial
Cancer of Ovary
Cancer of the Ovary
Neoplasms, Ovarian
Ovarian Cancer
Ovary Cancer
Ovary Neoplasms
Breast Cancer
Breast Carcinoma
Breast Tumors
Cancer of Breast
Cancer of the Breast
Human Mammary Carcinoma
Malignant Neoplasm of Breast
Malignant Tumor of Breast
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05067972
Org Class
Industry
Org Full Name
Pfizer
Org Study Id
C4431001
Overall Status
Terminated
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMIC, AND ANTITUMOR ACTIVITY OF PF-07260437 IN ADVANCED OR METASTATIC SOLID TUMORS
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of Participants With Dose-Limiting Toxicities (DLTs) in Dose Escalation - Part 1
Outcome Time Frame
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.
Outcome Description
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.
Outcome Measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs) - Part 1
Outcome Time Frame
Baseline (Day 1 of dosing ) through 4 week follow-up, up to 35.1 weeks
Outcome Description
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.
Outcome Measure
Number of Participants With Clinically Significant Laboratory Abnormalities - Part 1
Outcome Time Frame
Baseline through up to 35.1 weeks
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Day 1 up to 90 days after the last dose of study intervention (Day 246 [C9D15]), up to approximately 336 days
Outcome Measure
Number of Participants With Immune-Related Adverse Events (irAEs)
Outcome Description
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.
Outcome Time Frame
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.
Outcome Measure
Number of Participants by Categories of Anti-Drug Antibody (ADA) Against PF-07260437
Outcome Description
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.
Outcome Time Frame
Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1
Outcome Measure
Single Dose: Maximal Concentration (Cmax)
Outcome Description
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.
Outcome Time Frame
Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1
Outcome Measure
Single Dose: Area Under the Curve (AUCtau)
Outcome Description
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.
Outcome Time Frame
Day 1 pre-dose, 1, 4, 8, 24, 48 and 168 hours post-dose, till Day 15 pre-dose in Cycle 1
Outcome Measure
Single Dose: Time to Maximal Plasma Concentration (Tmax)
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jinyu Lu
Investigator Email
jilu@montefiore.org