PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers

Assess the efficacy with respect to clinical benefit rate (CBR) (Complete Response (CR)+ partial response (PR)+ stable disease (SD) for 4 months according to Response Evaluation Criteria (RECIST 1.1) of a combination of PLX038(PEGylated SN38) and rucaparib in previously treated participants with small cell lung cancer and extra-pulmonary small cell carcinomas. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. 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. 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.

Time frame: Disease progression at 4 months

Population: This outcome measure was not done because the study was closed to enrollment due to Clovis Oncology withdrawing support for the study. No data was collected for this phase II outcome measure.

Maximum tolerated dose (MTD) of PLX038 (PEGylated SN38) in combination with rucaparib. The MTD is the dose level at which no more than 1 of 6 participants experience dose limiting toxicity (DLT) during the DLT evaluation period, and the dose below that at which at least 2 (of 6) participants have DLT as a result of the drug. A DLT is (if deemed drug-related) a Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated with hemorrhage; Grade 4 anemia that does not resolve within 7 days despite optimal therapy; Inability to begin subsequent treatment course within 21 days of the scheduled date, due to study drug toxicity.

Time frame: One cycle, approximately 21 (+7) days

The safety of the treatment will be monitored, and any toxicities identified will be reported by type and grade. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Time frame: Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.

Population: Data is reported for the phase I portion only because the study was closed to enrollment prior to phase II due to Clovis Oncology withdrawing support for the study.

Among participants in the phase IIA cohort, median overall survival (OS) will be calculated from the on-study date using the Kaplan-Meier method, along with 95% confidence intervals on the median OS.OS is defined as the date of on-study to the date of death from any cause or last follow-up.

Time frame: Date of on-study to the date of death from any cause or last follow-up

Population: This outcome measure was not done because the study was closed to enrollment due to Clovis Oncology withdrawing support for the study. No data was collected for this phase IIA outcome measure.

Among participants in the phase IIA cohort, median progression free survival (PFS) will be calculated from the on-study date using the Kaplan-Meier method, along with 95% confidence intervals on the median PFS. PFS is defined as the time from on-study date to documented evidence of disease progression. Disease progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And appearance of one or more new lesions.

Time frame: Time from the on-study date to documented evidence of disease progression

Population: This outcome measure was not done because the study was closed to enrollment due to Clovis Oncology withdrawing support for the study. No data was collected for this phase IIA outcome measure.

The number of participants who experience a clinical response (Complete Response (CR)+Partial Response (PR) will be reported. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions; any pathological lymph nodes must have reduction in short axis to \<10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Time frame: Disease progression, a median of 43 days with range of 20 to 350 days.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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.

Time frame: Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.

A DLT is (if deemed drug-related) Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated with hemorrhage; Grade 4 anemia that does not resolve within 7 days despite optimal therapy; Inability to begin subsequent treatment course within 21 days of the scheduled date, due to study drug toxicity.

Time frame: One cycle, approximately 21 days