Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
PF-05212384 · 3 trials · 3 indications
DLT was defined as any of the following adverse events (AEs) attributable to the combination: (1) hematologic: grade 4 neutropenia lasting \>7 days; febrile neutropenia; grade \>=3 neutropenia with infection; grade 3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade \>=2 pneumonitis; grade\>=3 toxicities, except pneumonitis, and excluding those that had not been maximally treated; persistent, intolerable toxicities which resulted in the failure to deliver at least 3 of the 4 doses of PF-05212384 for Arms A and B or at least 3 of the 4 doses of PF-05212384 and 75% of dacomitinib for Arm C during the first cycle; the persistent, intolerable toxicities which result in delay of the start of the second cycle by more than 2 weeks relative to the scheduled start; in an asymptomatic participant, the grade 3 QTc prolongation persists after correction of any reversible causes.
Percentage of participants with objective response based on the assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm) and no new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs included both serious and non-serious adverse events.
Criteria for laboratory test abnormality: hematology (hemoglobin \[less than {\<} 0.8\*lower limit of normal {LLN}\], platelets \[\<0.5\*LLN or greater than {\>} 1.75\*upper limit of normal {ULN}\], white blood cells \[\<0.6\*LLN or \>1.5\*ULN\], lymphocytes \[\<0.8\*LLN or \>1.2\*ULN\], total neutrophils \[\<0.8\*LLN or \>1.2\*ULN\], basophils, eosinophils, monocytes \[\>1.2\*ULN\]); coagulation \[partial thromboplastin time, prothrombin (PT), PT international ratio \[\>1.1\*ULN\]); liver function (total bilirubin \[\>1.5\*ULN\], aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase \[\>0.3\*ULN\], total protein, albumin \[\<0.8\*LLN or \>1.2\*ULN\]).
DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: Grade 3 nonhematologic AE (including nausea, vomiting, or diarrhea despite optimal therapy; or greater than or equal to \[\>=\] grade 3 asthenia \>2 days; or fasting serum glucose \>250 milligrams per deciliter (mg/dL) despite optimal therapy); \>=Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia lasting more than 7 days; Febrile neutropenia; other Grade 4 hematologic AE; delay of treatment \>2 consecutive weeks due to toxicity. Grades were based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
RP2D of PF-05212384 was determined based on the safety profile including laboratory and clinical assessments and pharmacodynamics findings.
| Arm | Type | Description |
|---|---|---|
| [14C] PF 05212384 | EXPERIMENTAL | Receive PF-05212384 89 mg Dose |
| Arm A | EXPERIMENTAL | - |
| Arm B | EXPERIMENTAL | - |
| Arm C | EXPERIMENTAL | - |
| Expansion Arm 1 | EXPERIMENTAL | - |
| Expansion Arm 2 | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | PF-05212384 (also known as PKI-587) |
| Name | Type | Description |
|---|---|---|
| PF-05212384 | DRUG | Single 89 mg Dose via 30 minute IV infusion |
| PF-05212384 (gedatolisib) | DRUG | PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle |
| Docetaxel | DRUG | Docetaxel intravenous infusions once every 3 weeks starting at 75 mg/m\^2 |
| Cisplatin | DRUG | Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m\^2 |
| Dacomitinib | DRUG | Dacomitinib to be taken orally as a continuous once daily regimen at a starting dose of 30 mg |
| PF-05212384 (also known as PKI-587) | DRUG | Intravenous dosing once weekly infusion |
Inclusion Criteria: * Healthy male subjects between the ages of 30- 65 years vasectomised or \>40 with no desire to father children in the near future (12 months), inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examinati...
PF-05212384 is an investigational small molecule being studied for the treatment of neoplasms, including solid tumors and triple negative breast cancer. It has also been evaluated in healthy volunteers for metabolism and excretion studies. The drug is in Phase 1 clinical development and is not yet approved.
PF-05212384 is being developed by Pfizer, Inc., a biopharmaceutical company listed on the New York Stock Exchange under the ticker symbol PFE. The drug is currently in Phase 1 clinical trials, and Pfizer is conducting studies to evaluate its safety and efficacy in patients with various cancers.
PF-05212384 is in Phase 1 clinical development. All three clinical trials for the drug have been completed, and there are no active trials currently enrolling. The drug is investigational and has not received regulatory approval for any indication.
PF-05212384 has been studied in three completed Phase 1 trials. NCT00940498 evaluated the drug intravenously in patients with solid tumors. NCT01920061 tested it in combination with other anti-tumor agents and cisplatin in triple negative breast cancer. NCT02142920 investigated its metabolism and excretion in healthy male volunteers.
Yes, PF-05212384 is also known as PKI-587. In clinical trial NCT00940498, the study title refers to the drug as PF-05212384 (Also Known as PKI-587). This alternative name may appear in scientific literature and other references to the drug.