SC-004 Alone or With ABBV-181 in Subjects With Epithelial Ovarian, Fallopian Tube, Primary Peritoneal and Endometrial Cancers

Study Overview
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Brief Summary
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This is a two-part study consisting of Part A (dose regimen finding) followed by Part B (dose expansion). Part A (dose regimen finding) will allow definition of the maximum tolerated dose (MTD) through dose escalation and possible dose interval modification. In Part B (dose expansion), potential therapeutic doses may be studied with SC-004 as monotherapy and SC-004 in combination with ABBV-181 in disease-specific cohorts.

Official Title
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An Open Label, Phase 1 Study of SC-004 as Monotherapy and in Combination With ABBV-181 in Subjects With Epithelial Ovarian, Including Fallopian Tube and Primary Peritoneal and Endometrial Cancers

Conditions
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Cancer

Intervention / Treatment
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* Drug: SC-004
* Drug: ABBV-181


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed advanced malignancy defined as any of the following tumors for which no further standard or curative therapy exists or is considered appropriate by the Investigator: Epithelial ovarian cancer, including fallopian tube cancer or primary peritoneal cancer, of high-grade serous histology, with platinum refractory or resistant disease after prior treatment with at least one platinum-based chemotherapeutic regimen. In Part B (dose expansion), subjects may have received no more than 3 lines of systemic cytotoxic chemotherapy. Note, the line of therapy limit does not apply to the biopsy substudy cohorts. Metastatic or advanced endometrial carcinoma previously treated with at least 1 platinum-based chemotherapeutic regimen. Eastern Cooperative Oncology Group (ECOG) 0-1. Adequate hematologic, hepatic, and renal function. Exclusion Criteria: Participants with prior exposure to a pyrrolobenzodiazepine or indolinobenzodiazepine based drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SC-004<br> | Drug: SC-004<br>* Intravenous<br>|
| Experimental: SC-004 and ABBV-181<br> | Drug: SC-004<br>* Intravenous<br>Drug: ABBV-181<br>* Intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose-limiting toxicities (DLT) | DLTs graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. | Minimum first cycle of dosing (21-day cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed plasma concentrations at trough (Ctrough) | Observed plasma concentrations at trough. | Approximately 1 year | 
| Overall Survival (OS) | OS is defined as the time from the subject's first dose date to death due to any cause. | Approximately 2 years | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of subjects with complete response or partial response (CR+PR). | Approximately 2 years | 
| Terminal half life (T1/2) | Terminal half life (T1/2). | Approximately 1 year | 
| Maximum observed serum concentration (Cmax) | Maximum observed serum concentration. | Approximately 1 year | 
| Time to Cmax (Tmax) | Time to Cmax. | Approximately 1 year | 
| Clinical Benefit Rate (CBR) | CBR is defined as the proportion of subjects with an objective response or stable disease (CR+PR+SD). | Approximately 2 years | 
| Progression Free Survival (PFS) | PFS time is defined as the time from the subject's first dose of study drug (Day 1) to either the subject's disease progression or death due to any cause, whichever occurs first. Under the situation that neither event occurs, the PFS time will be censored at the date of last tumor assessment. Subjects lacking an evaluation of tumor response after their first dose of study treatment will have their event time censored at Day 1. | Approximately 2 years | 
| Duration of Response (DOR) | DOR is defined as the time from the subject's initial objective response (CR or PR) to study drug therapy to disease progression or death due to any cause, whichever occurs first. If the dates of disease progression or death are not available, the DOR will be censored at the date of last valid tumor assessment. | Approximately 2 years | 
| Area under the plasma concentration-time curve within a dosing interval (AUC) | Area under the plasma concentration-time curve within a dosing interval. | Approximately 1 year | 
| QTcF Change from Baseline | QT interval measurement corrected by Fridericia's formula (QTcF). | Up to 9 weeks based on 3 cycles of dosing (21-day cycles) | 
| Duration of Clinical Benefit (DOCB) | DOCB is defined as the time from a subject's objective response (CR or PR) or stable disease (SD) to study drug therapy to disease progression or death due to any cause whichever occurs first. | Approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian cancer, Endometrial cancer, SC-004, Maximum tolerated dose (MTD), ABBV-181