Description:
This is an international, randomized, open-label, Phase 3 study designed to evaluate whether
the potent and selective RET inhibitor, pralsetinib, improves outcomes when compared to a
platinum chemotherapy-based regimen chosen by the Investigator from a list of standard of
care treatments, as measured primarily by progression free survival (PFS), for participants
with RET fusion-positive metastatic NSCLC who have not previously received systemic
anticancer therapy for metastatic disease. Participants who have centrally confirmed
progressive disease on the control arm have the option to crossover to pralsetinib.
Title
- Brief Title: A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
- Official Title: A Phase III, Randomized, Open-Label Study of Pralsetinib Versus Standard of Care for First-Line Treatment of RET Fusion-Positive, Metastatic Non-Small Cell Lung Cancer
Clinical Trial IDs
- ORG STUDY ID:
BO42864
- SECONDARY ID:
2019-002463-10
- SECONDARY ID:
BLU-667-2303
- NCT ID:
NCT04222972
Conditions
- RET-fusion Non Small Cell Lung Cancer
- Lung Neoplasm
- Carcinoma, Non-Small-Cell Lung
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Neoplasms by Site
- Neoplasms
- Lung Diseases
- Respiratory Tract Disease
- Carcinoma, Bronchogenic
- Bronchial Diseases
- Head and Neck Neoplasms
- Adenocarcinoma
- Carcinoma
- Neoplasms by Histologic Type
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
Interventions
| Drug | Synonyms | Arms |
|---|
| Pralsetinib | BLU-667 | Pralsetinib |
| Carboplatin | | Platinum-based chemotherapy with or without pembrolizumab |
| Cisplatin | | Platinum-based chemotherapy with or without pembrolizumab |
| Pemetrexed | | Platinum-based chemotherapy with or without pembrolizumab |
| Pembrolizumab | | Platinum-based chemotherapy with or without pembrolizumab |
| Gemcitabine | | Platinum-based chemotherapy with or without pembrolizumab |
| Paclitaxel | | Platinum-based chemotherapy with or without pembrolizumab |
| Nab-Paclitaxel | | Platinum-based chemotherapy with or without pembrolizumab |
Purpose
This is an international, randomized, open-label, Phase 3 study designed to evaluate whether
the potent and selective RET inhibitor, pralsetinib, improves outcomes when compared to a
platinum chemotherapy-based regimen chosen by the Investigator from a list of standard of
care treatments, as measured primarily by progression free survival (PFS), for participants
with RET fusion-positive metastatic NSCLC who have not previously received systemic
anticancer therapy for metastatic disease. Participants who have centrally confirmed
progressive disease on the control arm have the option to crossover to pralsetinib.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Pralsetinib | Experimental | Participants randomized to the Experimental Arm will receive Pralsetinib | |
| Platinum-based chemotherapy with or without pembrolizumab | Active Comparator | Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)
Nonsquamous histology
Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
Squamous histology
Carboplatin or cisplatin / gemcitabine
Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab | - Carboplatin
- Cisplatin
- Pemetrexed
- Pembrolizumab
- Gemcitabine
- Paclitaxel
- Nab-Paclitaxel
|
Eligibility Criteria
Inclusion criteria:
- Participant has pathologically confirmed, definitively diagnosed, locally advanced
(not able to be treated with surgery or radiotherapy) or metastatic NSCLC and has not
been treated with systemic anticancer therapy for metastatic disease.
- Participant must have a documented RET-fusion
- Participant has measurable disease based on RECIST 1.1 as determined by the local site
Investigator/radiology assessment.
- Participant has an ECOG Performance Status of 0 or 1.
- Participant should not have received any prior anticancer therapy for metastatic
disease.
- Participants can have received previous anticancer therapy (except a selective
RET inhibitor) in the neoadjuvant or adjuvant setting but must have experienced
an interval of at least ≥ 6 months from completion of therapy to recurrence.
- Participants that received previous immune checkpoint inhibitors in the adjuvant
or consolidation following chemoradiation are not allowed to receive
pembrolizumab if randomized in Arm B
- Participant is an appropriate candidate for and agrees to receive 1 of the
Investigator choice platinum-based chemotherapy regimens if randomized to Arm B.
- For women of childbearing potential: participants who agree to remain abstinent
(refrain from heterosexual intercourse) or use contraception.
- For men: participants who agree to remain abstinent (refrain from heterosexual
intercourse) or use a condom and agree to refrain from donating sperm.
Exclusion criteria:
- Participant's tumor has any additional known primary driver alterations other than
RET, such as targetable mutations of EGFR, ALK, ROS1, MET, and BRAF. Investigators
should discuss enrollment with Sponsor designee regarding co-mutations.
- Participant previously received treatment with a selective RET inhibitor.
- Participant received radiotherapy or radiosurgery to any site within 14 days before
randomization or more than 30 Gy of radiotherapy to the lung in the 6 months before
randomization.
- Participant with a history of pneumonitis within the last 12 months.
- Participant has CNS metastases or a primary CNS tumor that is associated with
progressive neurological symptoms or requires increasing doses of corticosteroids to
control the CNS disease. If a participant requires corticosteroids for management of
CNS disease, the dose must have been stable for the 2 weeks before Cycle 1 Day 1.
- Participant has had a history of another primary malignancy that has been diagnosed or
required therapy within the past 3 years prior to randomization.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | Estimated at up to 32 months |
| Safety Issue: | |
| Description: | Defined as the time from randomisation date to the first documented progressive disease (PD), as assessed by Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 central imaging review or death due to any cause, whichever occurs first. |
Secondary Outcome Measures
| Measure: | Overall Response Rate (ORR) |
| Time Frame: | Estimated at up to 32 months |
| Safety Issue: | |
| Description: | Defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as assessed by BICR according to RECIST 1.1 central imaging review. |
| Measure: | Overall Survival (OS) |
| Time Frame: | Estimated at approximately 32 months |
| Safety Issue: | |
| Description: | Defined as the time from randomisation date to death due to any cause. |
| Measure: | Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| Time Frame: | Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months) |
| Safety Issue: | |
| Description: | The intensity of Adverse Events (AEs) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0). |
| Measure: | Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS) |
| Time Frame: | Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months) |
| Safety Issue: | |
| Description: | Further characterising safety and tolerability. |
| Measure: | Duration of Response (DOR) |
| Time Frame: | Estimated at up to 32 months |
| Safety Issue: | |
| Description: | Defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as assessed by BICR according to RECIST v1.1. |
| Measure: | Clinical Benefit Rate (CBR) |
| Time Frame: | Estimated at up to 32 months |
| Safety Issue: | |
| Description: | Defined as the proportion of participants who experience a best response of Stable Disease (SD) with a minimum duration of 6 months, a CR, or a PR, as assessed by BICR according to RECIST v1.1. |
| Measure: | Disease Control Rate (DCR) |
| Time Frame: | Estimated at up to 32 months |
| Safety Issue: | |
| Description: | Defined as the proportion of participants who experience a best response of CR, or PR, or SD, as assessed by BICR according to RECIST v1.1. |
| Measure: | European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-C30 Questionnaires |
| Time Frame: | From baseline until progressive disease or death (estimated 32 months) |
| Safety Issue: | |
| Description: | 0-100 points (lower score represents worse quality of life) |
| Measure: | European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-LC13 Scores |
| Time Frame: | From baseline until progressive disease or death (estimated 32 months) |
| Safety Issue: | |
| Description: | The item scale ranges from 1-4 (1 = Not at all; 4 = Very Much) where the EORTC-QLQ-LC13 scoring algorithm is applied to convert to a 0-100 point scale where 100 is best quality of life (QOL), for comparability. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
Trial Keywords
- Advanced Non-Small Cell Lung Cancer
- RET Lung
- RET Mutation
- RET Alteration
- RET Positive
- RET Inhibitor
- RET Altered
- RET Rearrangement
- RET NSCLC
- RET-Rearranged NSCLC
- RET Fusion
- RET Fusion Lung Cancer
- M918T
- TRIM33-RET
- Lung Cancer Mutation
- BLU 667
- Pralsetinib
- RET Tyrosine Kinase
- RET Gene Mutation
- RET Kinase
- Advanced Lung Cancer
- Metastatic Lung Cancer
- KIF5B-RET
- CCDC6-RET
Last Updated
May 27, 2021
