A Phase I/II Trial of Topotecan With VX-970 (M6620), an ATR Kinase Inhibitor in Small Cell Cancers

Ph I: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Topotecan

时间窗: End of Cycle 1, approximately 3 weeks

MTD is defined as the dose level at which no more than 1 of 6 subjects experience a dose-limiting toxicity (DLT) during one cycle of treatment. A DLT is defined using the Common Terminology Criteria in Adverse Events (CTCAE) v4.0 and is related or possibly drug related, such as neutropenia Grade 4 for \>7 days duration, febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection), or Grade 3 thrombocytopenia. Death due to drug related adverse events.

Ph II: Number of Participants With a Clinical Response

时间窗: Every two cycles (each cycle is 21 days) up to approximately 30 months.

Clinical response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

时间窗: Date treatment consent signed to date off study, approximately 9 months and 9 days for Ph I DL1, 42 months and 12 days for Ph I DL2, 15 months and 9 days for Ph I DL3, 17 months and 9 days for Ph I DL4, and 43 months and 22 days for Ph II DL4.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Ph I: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of VX-970 (M6620)

时间窗: End of Cycle 1, approximately 3 weeks

MTD is defined as the dose level at which no more than 1 of 6 subjects experience a dose-limiting toxicity (DLT) during one cycle of treatment. A DLT is defined using the Common Terminology Criteria in Adverse Events (CTCAE) v4.0 and is related or possibly drug related, such as neutropenia Grade 4 for \>7 days duration, febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection), or Grade 3 thrombocytopenia. Death due to drug related adverse events.