A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES OF PF-06939999 (PRMT5 INHIBITOR) IN PARTICIPANTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER, HEAD AND NECK SQUAMOUS CELL CARCINOMA, ESOPHAGEAL CANCER, ENDOMETRIAL CANCER, CERVICAL CANCER AND BLADDER CANCER

Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)

时间窗: Baseline through day 29.

DLTs=any of the following adverse events (AEs) occurring in the DLT observation period (first treatment cycle):1) Any Grade 4 hematologic AEs; Grade 4 neutropenia, febrile neutropenia, Grade 3 neutropenia with infection, Grade 3 thrombocytopenia with ≥Grade 2 clinically significant bleeding, Grade 3 anemia requiring blood transfusion; 2) Any Grade ≥3 non-hematologic AEs; Grade 3 nausea/vomiting or diarrhea lasting ≥4 days after treatment, confirmed drug induced liver injury meeting Hy's law criteria; a hepatic transaminase or alkaline phosphatase level \>10 times the upper limit of normal for participants with Grade 2 hepatic transaminase or alkaline phosphatase levels at baseline as a result of liver/bone metastasis; clinically important or persistent toxicities; 3) Any toxicity causing \>2 weeks of dose delay; 4) any dose reduction due to AE during the first cycle. Grades of AEs were defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

Part 1A: Number of Participants With Treatment-Emergent Adverse Events (TEAE)

时间窗: Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 13 months)

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. A serious adverse event (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. Grades of AEs were defined by NCI CTCAE version 5.0. Grade 3 events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events = events that caused participant to be in imminent danger of death. Grade 5 events = death related to an AE.

Part 1A: Number of Participants With Laboratory Abnormalities

时间窗: Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 12 months)

Laboratory assessments included hematology, chemistry and urinary tests. Participants with maximum Grade 3-4 laboratory abnormalities are reported in this OM. Grades of laboratory results were defined by NCI CTCAE version 5.0. Grade 3 events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events = events that caused participant to be in imminent danger of death. Some of the Grade 4 events (activated partial thromboplastin time prolonged, anemia, hemoglobin increased, leukocytosis, lymphocyte count increased and hypoalbuminemia) could not be defined/determined based only on lab data, therefore are not reported in this OM.

Part 2: Number of Participants With TEAEs

时间窗: Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 15 months)

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. A serious adverse event (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. Grades of AEs were defined by NCI CTCAE version 5.0. Grade 3 events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events = events that caused participant to be in imminent danger of death. Grade 5 events = death related to an AE.

Part 2: Number of Participants With Laboratory Abnormalities

时间窗: Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 8 months)

Laboratory assessments included hematology, chemistry and urinary tests. Participants with maximum Grade 3-4 laboratory abnormalities are reported in this OM. Grades of laboratory results were defined by NCI CTCAE version 5.0. Grade 3 events = unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events = events that caused participant to be in imminent danger of death. Some of the Grade 4 events (activated partial thromboplastin time prolonged, anemia, hemoglobin increased, leukocytosis, lymphocyte count increased and hypoalbuminemia) could not be defined/determined based only on lab data, therefore are not reported in this OM.

Part 2: Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment (RECIST, Version 1.1)

时间窗: From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months).

Number of participants with BOR assessed using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1: Complete Response (CR): disappearance of all lesions (with the exception of nodal disease when assessing target lesions). Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered a sign of progression. Stable disease (SD): does not qualify for CR, PR or PD. Non-CR/Non-PD: Persistence of any non target lesions and/or tumor marker level above the normal limits.