Phase 2
Completed N=98
A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)
Ovarian Cancer · Fallopian tube cancer · Peritoneal Cancer
Source: ClinicalTrials.gov NCT03657043 ↗
Enrolled (actual)
98
Serious AEs
36.2%
Results posted
May 2023
Primary outcomePrimary: Number of Participants With Dose-Limiting Toxicities (DLTs) (Safety Run-In Only) — 0; 1 Participants
Summary
This trial will study tisotumab vedotin to find out what its side effects are and to see if it works for platinum-resistant ovarian cancer (PROC). It will test different doses of tisotumab vedotin that are given at different times. It will also compare the side effects and ability to treat tumors of these different doses and schedules. In this study, there will be a safety run-in group of approximately 12 patients that will look at a dose-dense treatment schedule. In a dose-dense schedule, smaller doses are given more frequently. In addition to the safety run-in patients, there will be three groups in the study. One group will get tisotumab vedotin once every 3 weeks (21-day cycles). The two other groups will get tisotumab vedotin once a week for 3 weeks followed by 1 week off (28-day cycles).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-Limiting Toxicities (DLTs) (Safety Run-In Only) |
0; 1 | — |
| PRIMARY Confirmed Objective Response Rate (ORR) (Part B) |
7 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) (Part B) |
79; 67; 14; 0; 7; 35 | — |
| SECONDARY Confirmed and Unconfirmed ORR (Part B) |
18.0 | — |
| SECONDARY Cancer Antigen 125 (CA-125) Response Rate According to Gynecologic Cancer Intergroup (GCIG) Criteria (Part B) |
12.0 | — |
| SECONDARY Overall Response According to the Gynecological Cancer Intergroup (GCIG) Combined RECIST and CA-125 Criteria (Part B) |
11.0 | — |
| SECONDARY Duration of Response (DOR) (Part B) |
4.21 | — |
| SECONDARY Disease Control Rate (DCR) (Part B) |
54.4 | — |
| SECONDARY Time to Response (TTR) (Part B) |
1.4 | — |
| SECONDARY Progression-free Survival (PFS) (Part B) |
2.73 | — |
| SECONDARY Overall Survival (OS) (Part B) |
10.68 | — |
| SECONDARY Incidence of Antitherapeutic Antibodies (ATA) (Part B) |
65; 3; 3; 0 | — |
| SECONDARY Pharmacokinetic (PK) Parameter: Antibody-Drug Conjugate (ADC) Maximum Concentration (Cmax) (Part B) |
20.582; 21.817 | — |
| SECONDARY PK Parameter: ADC Time of Cmax (Tmax) (Part B) |
0.041; 0.041 | — |
| SECONDARY PK Parameter: ADC Area Under Concentration-Time Curve (AUC) (Part B) |
25.198; 30.159; 31.716 | — |
| SECONDARY PK Parameter: Free Monomethyl Auristatin E (MMAE) Cmax (Part B) |
1.778; 2.552 | — |
| SECONDARY PK Parameter: MMAE Tmax (Part B) |
2.061; 2.101 | — |
| SECONDARY PK Parameter: MMAE AUC (Part B) |
8.709; 16.578 | — |
| SECONDARY PK Parameter: MMAE Trough Concentration (Ctrough) (Part B) |
0.230 | — |
| SECONDARY PK Parameter: Total Antibody (TAb) Cmax (Part B) |
18.418; 19.955 | — |
| SECONDARY PK Parameter: TAb Tmax (Part B) |
0.041; 0.043 | — |
| SECONDARY PK Parameter: TAb Area Under Concentration-Time Curve (AUC) (Part B) |
35.535; 39.371; 42.240 | — |
Eligibility Criteria
Inclusion Criteria
- Histologic documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
- Safety run-in only: PROC. Patients may have received more than 1 prior systemic treatment regimen in the PROC setting.
- Part A and Part B only: Patients with PROC who have received 1 to 3 anticancer lines of therapy overall, including at least 1 line of therapy containing bevacizumab or biosimilar.
- Adjuvant ± neoadjuvant are considered 1 line of therapy.
- Patients may have received a PARP inhibitor or an immuno-oncology (IO) agent; any of these regimens are to be considered a line of therapy for the purposes of this study if not used as maintenance therapy.
- Maintenance therapy (including bevacizumab, PARP inhibitors and IOs) will be considered part of the preceding line of therapy and not to be counted as a new line of therapy.
- Any chemotherapy regimen change due to toxicity in the absence of disease progression is considered as part of the same line of therapy.
- Hormonal therapy will be not be counted towards the lines of therapy.
- Measurable disease according to RECIST v1.1 as assessed by the investigator
- An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Life expectancy of at least 3 months
- Able to provide fresh or archival tissue for biomarker analysis
Exclusion Criteria
- Primary platinum-refractory disease, defined as disease progression within 2 months of completion of first line platinum-based therapy
- Patients with clinical symptoms or signs of gastrointestinal obstruction with the past 6 months or who currently require parenteral nutrition
- Hematological: Known past or current coagulation defects leading to an increased risk of bleeding, diffuse alveolar hemorrhage from vasculitis, known bleeding diathesis, ongoing major bleeding, or trauma with increased risk of life-threatening bleeding within 8 weeks of trial entry
- Cardiovascular: Clinically significant cardiac disease including uncontrolled hypertension, unstable angina, acute myocardial infarction with 6 months of screening, serious cardiac arrhythmia requiring medication, medical history of congestive heart failure, or medical history of decreased cardiac ejection fraction of 1 peripheral neuropathy
- Patients who are pregnant or breastfeeding
Data sourced from ClinicalTrials.gov (NCT03657043). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.