Trial Outcomes & Findings for PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers (NCT NCT04209595)

NCT ID: NCT04209595

Last Updated: 2025-03-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Disease progression at 4 months

Results posted on

2025-03-17

Participant Flow

The phase II portion of the study was not done because the study was closed to enrollment due to Clovis Oncology withdrawing support for the study.

Participant milestones

Participant milestones
Measure	Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.
Phase I - Maximum Tolerated Dose STARTED	8	2
Phase I - Maximum Tolerated Dose COMPLETED	8	2
Phase I - Maximum Tolerated Dose NOT COMPLETED	0	0
Phase IIA - Assess Efficacy STARTED	0	0
Phase IIA - Assess Efficacy COMPLETED	0	0
Phase IIA - Assess Efficacy NOT COMPLETED	0	0
Phase IIB - Assess Efficacy STARTED	0	0
Phase IIB - Assess Efficacy COMPLETED	0	0
Phase IIB - Assess Efficacy NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: One cycle, approximately 21 (+7) days

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.

Outcome measures

Outcome measures
Measure	Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg n=10 Participants Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I Arm 1 Level 1 - Related to Rucaparib Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.	Phase I - Arm 1 Level 1A - Related to Rucaparib Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.
Phase I: Maximum Tolerated Dose (MTD) of PLX038 (PEGylated SN38) in Combination With Rucaparib	NA g/m^2 MTD was not reached because dose escalation was not completed.	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg n=8 Participants Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg n=2 Participants Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I Arm 1 Level 1 - Related to Rucaparib n=8 Participants Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.	Phase I - Arm 1 Level 1A - Related to Rucaparib n=2 Participants Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Aspartate aminotransferase increased	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Diarrhea	8 Adverse events	1 Adverse events	9 Adverse events	3 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Dysuria	3 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Intestinal stoma site bleeding	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Nausea	2 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Hypokalemia	1 Adverse events	4 Adverse events	1 Adverse events	3 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Alanine aminotransferase increased	0 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Abdominal pain	2 Adverse events	1 Adverse events	4 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Alopecia	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Anemia	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Anorexia	3 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Bloating	4 Adverse events	1 Adverse events	3 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Blood bicarbonate decreased	0 Adverse events	2 Adverse events	0 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Bruising	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Chills	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Constipation	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Dysgeusia	1 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Fatigue	4 Adverse events	0 Adverse events	4 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Flatulence	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 4 Non-Serious White blood cell decreased	1 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 5 Serious Gastrointestinal disorders - Other specify	0 Adverse events	2 Adverse events	0 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Lymphocyte count decreased	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Urinary frequency	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Nausea	5 Adverse events	0 Adverse events	5 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Neutrophil count decreased	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Platelet count decreased	5 Adverse events	4 Adverse events	5 Adverse events	4 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Pruritis	2 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Rectal hemorrhage	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious Vomiting	3 Adverse events	1 Adverse events	3 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 1 Non-Serious White blood cell decreased	2 Adverse events	1 Adverse events	2 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Abdominal pain	3 Adverse events	0 Adverse events	6 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Alopecia	3 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Anemia	7 Adverse events	4 Adverse events	7 Adverse events	4 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Bloating	2 Adverse events	0 Adverse events	3 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Diarrhea	5 Adverse events	0 Adverse events	6 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Fatigue	3 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Flatulence	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Gastroesophageal reflux disease	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Lymphocyte decreased	4 Adverse events	0 Adverse events	4 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Neutrophil count decreased	3 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Non-Serious Neutrophil count decreased	3 Adverse events	1 Adverse events	3 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Platelet count decreased	2 Adverse events	2 Adverse events	2 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Pruritis	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious Vomiting	3 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 2 Non-Serious White blood cell decreased	2 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Non-Serious Abdominal pain	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Serious Anemia	5 Adverse events	2 Adverse events	5 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Serious Diarrhea	2 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Serious Gastrointestinal disorders - Other specify	0 Adverse events	1 Adverse events	0 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Non-Serious Lymphocyte count decreased	4 Adverse events	1 Adverse events	4 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Serious Nausea	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Non-Serious Platelet count decreased	4 Adverse events	2 Adverse events	4 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Serious Vomiting	1 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 3 Non-Serious White blood cell decreased	5 Adverse events	1 Adverse events	5 Adverse events	2 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 4 Serious Febrile neutropenia	1 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 4 Non-Serious Lymphocyte count decreased	3 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 4 Non-Serious Neutrophil count decreased	1 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 4 Serious Platelet Count decreased	3 Adverse events	0 Adverse events	3 Adverse events	0 Adverse events
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib Grade 4 Serious Sepsis	1 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg n=8 Participants Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg n=2 Participants Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I Arm 1 Level 1 - Related to Rucaparib Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.	Phase I - Arm 1 Level 1A - Related to Rucaparib Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.
Phase I - Number of Participants Who Experience a Clinical Response (Complete Response (CR)+Partial Response (PR) Complete Response	1 Participants	0 Participants	—	—
Phase I - Number of Participants Who Experience a Clinical Response (Complete Response (CR)+Partial Response (PR) Partial Response	1 Participants	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: One cycle, approximately 21 days

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.

Outcome measures

Outcome measures
Measure	Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg n=8 Participants Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg n=2 Participants Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I Arm 1 Level 1 - Related to Rucaparib Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.	Phase I - Arm 1 Level 1A - Related to Rucaparib Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.
Phase I Number of Participants With a Dose Limiting Toxicity (DLT)	1 Participants	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

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

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.

Outcome measures

Outcome measures
Measure	Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg n=8 Participants Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg n=2 Participants Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I Arm 1 Level 1 - Related to Rucaparib Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.	Phase I - Arm 1 Level 1A - Related to Rucaparib Phase I - Participants with solid tumors with serious and/or non-serious adverse events related to Rucaparib.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	8 Participants	2 Participants	—	—

Adverse Events

Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg

Serious events: 3 serious events

Other events: 8 other events

Deaths: 7 deaths

Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg

Serious events: 2 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg n=8 participants at risk Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg n=2 participants at risk Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.
Blood and lymphatic system disorders Anemia	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	0.00% 0/2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Gastrointestinal disorders Diarrhea	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	0.00% 0/2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Gastrointestinal disorders Febrile neutropenia	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	50.0% 1/2 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Gastrointestinal disorders Gastrointestinal disorders - Other, Neutropenic Enterocolitis	0.00% 0/8 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	100.0% 2/2 • Number of events 3 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, Traumatic Head Injury	12.5% 1/8 • Number of events 2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	0.00% 0/2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	0.00% 0/2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Investigations Neutrophil count decreased	0.00% 0/8 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	50.0% 1/2 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Investigations Platelet count decreased	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	0.00% 0/2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Infections and infestations Sepsis	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	50.0% 1/2 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Nervous system disorders Syncope	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	0.00% 0/2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Nervous system disorders Vasovagal reaction	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	0.00% 0/2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Gastrointestinal disorders Vomiting	12.5% 1/8 • Number of events 1 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.	0.00% 0/2 • Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.

Other adverse events

Additional Information

Dr. Anish Thomas

National Cancer Institute

Phone: 240-760-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg n=8 Participants Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg n=2 Participants Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m\^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO) PLX038: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days). Rucaparib: Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	57.06 years STANDARD_DEVIATION 12.25 • n=5 Participants	59.75 years STANDARD_DEVIATION 4.17 • n=7 Participants	57.6 years STANDARD_DEVIATION 10.95 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	2 participants n=7 Participants	10 participants n=5 Participants