Description:
The purpose of this randomized, open-label, 2-arm, phase 3 study is to assess the efficacy,
safety and tolerability of rovalpituzumab tesirine versus topotecan in participants with
advanced or metastatic SCLC with high levels of DLL3, who have first disease progression
during or following front-line platinum-based chemotherapy.
Title
- Brief Title: Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)
- Official Title: A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)
Clinical Trial IDs
- ORG STUDY ID:
M16-289
- SECONDARY ID:
2016-003726-17
- NCT ID:
NCT03061812
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Rovalpituzumab tesirine | Rova-T | Rovalpituzumab tesirine |
| Topotecan | | Topotecan |
| Dexamethasone | | Rovalpituzumab tesirine |
Purpose
The purpose of this randomized, open-label, 2-arm, phase 3 study is to assess the efficacy,
safety and tolerability of rovalpituzumab tesirine versus topotecan in participants with
advanced or metastatic SCLC with high levels of DLL3, who have first disease progression
during or following front-line platinum-based chemotherapy.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Rovalpituzumab tesirine | Experimental | Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted.
Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered. | - Rovalpituzumab tesirine
- Dexamethasone
|
| Topotecan | Active Comparator | Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle. | |
Eligibility Criteria
Inclusion Criteria:
- Participant must have histologically or cytologically confirmed advanced or metastatic
Small Cell Lung Cancer (SCLC) with documented first disease progression during or
following front-line platinum-based systemic regimen
- Tumor must have high Delta-like protein 3 (DLL3) expression defined as having ≥ 75%
tumor cells staining positive according to the VENTANA DLL3 (SP347) IHC Assay.
- Participant must have measurable disease, as defined per Response Evaluation Criteria
in Solid Tumors (RECIST) version 1.1.
- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1.
- Participant must have recovery to Grade 0 or 1 of any clinically significant toxicity
(excluding alopecia) prior to initiation of study drug administration.
Exclusion Criteria:
- Participant has a documented history of a cerebral vascular event (stroke or transient
ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms
consistent with New York Heart Association Class (NYHA) III - IV within 6 months prior
to their first dose of study drug.
- Participant has known leptomeningeal metastases.
- Participant has received more than one prior systemic therapy regimen for SCLC.
- Participant had a serious infection within 2 weeks prior to randomization, including
any Grade 3 or higher viral, bacterial, or fungal infection.
- Participant has a history of active malignancies other than SCLC within the past 2
years prior to study entry, with the exception of in situ cancer which was curatively
treated.
- Participant had prior exposure to topotecan, irinotecan or any other topoisomerase I
inhibitors.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall Survival (OS) |
| Time Frame: | From randomization until the end of study; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively. |
| Safety Issue: | |
| Description: | OS is defined as the time from the date of randomization to the date of death from any cause. Participants were censored at the last date they were documented alive. After the End of treatment, survival information was collected at approximately 6-week intervals (or as requested by sponsor to support data analysis) continuing until the endpoint of death, the participant became lost to follow-up, AbbVie terminated the study, or until 12 February 2020. Calculated using the Kaplan-Meier product-limit method. |
Secondary Outcome Measures
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | From randomization until the end of study; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively. |
| Safety Issue: | |
| Description: | PFS is defined as the number of months from the date of randomization until the date of first progression or the date of a participant's death, whichever occurs first. If a participant neither experienced disease progression nor died, then the participant's data were censored at the last date of radiographic assessment that they were documented to be progression free. Calculated using the Kaplan-Meier product-limit method.
Radiographic tumor assessments for response were conducted by CT scanning according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Progressive Disease (PD) was defined as at least a 20% increase in the size of target lesions and an absolute increase of at least 5 mm taking as reference the smallest lesion size recorded since the treatment started (baseline or after), or the appearance of one or more new lesions. |
| Measure: | Change From Baseline of the Physical Functioning Scale Score in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL) at Week 7 |
| Time Frame: | Baseline, Week 7 |
| Safety Issue: | |
| Description: | The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC core quality of life questionnaire (EORTC QLQ-C30) developed for use in palliative care. The score of 'physical functioning scale' score ranges from 0 (very poor) to 100 (excellent). |
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively. |
| Safety Issue: | |
| Description: | ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST version 1.1. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR or PR, including those who did not have post-baseline radiological assessments were considered non-responders.
CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Measure: | Clinical Benefit Rate (CBR) |
| Time Frame: | Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively. |
| Safety Issue: | |
| Description: | CBR is defined as percentage of participants whose best overall response is CR, PR, or stable disease (SD) according to RECIST version 1.1. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR, PR, or SD, including those who did not have post-baseline radiological assessments were considered as experiencing no clinical benefit.
CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Measure: | Duration of Objective Response (DOR) |
| Time Frame: | Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively. |
| Safety Issue: | |
| Description: | DOR is defined as the time between the date of first response (CR or PR, whichever is recorded first) to the date of the first documented tumor progression (per RECIST version 1.1) or death due to any cause, whichever comes first. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR or PR, including those who did not have post-baseline radiological assessments were considered non-responders.
CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | AbbVie |
Trial Keywords
- Small cell lung cancer (SCLC)
- Delta-like protein 3 (DLL3)
- rovalpituzumab tesirine
- topotecan
- metastatic
Last Updated
February 23, 2021
