TriangleNCT04222972 · CITED IN SOURCE DOCUMENTS
A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- TERMINATED
- Registry last update
- 2026-03-05
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.
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Arm A vs Arm B: Treatment Period: Progression-free Survival (PFS)
Arm A vs Arm B: Objective Response Rate (ORR)
Arm A vs Arm B: Overall Survival (OS)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
Arm A vs Arm B: Duration of Response (DOR)
Arm A vs Arm B: Clinical Benefit Rate (CBR)
Arm A vs Arm B: Disease Control Rate (DCR)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants randomized to the Experimental Arm will receive Pralsetinib
- intervention Names
- Drug: Pralsetinib
- label
- Pralsetinib
- type
- EXPERIMENTAL
- description
- 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
- intervention Names
- Drug: Carboplatin
- Drug: Cisplatin
- Drug: Pemetrexed
- Drug: Pembrolizumab
- Drug: Gemcitabine
- Drug: Paclitaxel
- Drug: Nab-Paclitaxel
- label
- Platinum-based chemotherapy with or without pembrolizumab
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Pralsetinib
- description
- Administered orally
- name
- Pralsetinib
- other Names
- BLU-667
- type
- DRUG
- arm Group Labels
- Platinum-based chemotherapy with or without pembrolizumab
- description
- Administered IV
- name
- Carboplatin
- type
- DRUG
- arm Group Labels
- Platinum-based chemotherapy with or without pembrolizumab
- description
- Administered IV
- name
- Cisplatin
- type
- DRUG
- arm Group Labels
- Platinum-based chemotherapy with or without pembrolizumab
- description
- Administered IV
- name
- Pemetrexed
- type
- DRUG
- arm Group Labels
- Platinum-based chemotherapy with or without pembrolizumab
- description
- Administered IV
- name
- Pembrolizumab
- type
- DRUG
- arm Group Labels
- Platinum-based chemotherapy with or without pembrolizumab
- description
- Administered IV
- name
- Gemcitabine
- type
- DRUG
- arm Group Labels
- Platinum-based chemotherapy with or without pembrolizumab
- description
- Administered IV
- name
- Paclitaxel
- type
- DRUG
- arm Group Labels
- Platinum-based chemotherapy with or without pembrolizumab
- description
- Administered IV
- name
- Nab-Paclitaxel
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 223
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- PFS was defined as the time from randomization to the date of first documented PD as determined by the investigator with the use of Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm). Kaplan-Meier (K-M) method was used to estimate median PFS. 95% CI for median was computed using the method of Brookmeyer and Crowley.
- measure
- Arm A vs Arm B: Treatment Period: Progression-free Survival (PFS)
- time Frame
- Up to approximately 50 months
- secondary Outcomes
- description
- ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. 95% CI for rates were constructed using the Clopper-Pearson method. Percentages have been rounded off.
- measure
- Arm A vs Arm B: Objective Response Rate (ORR)
- time Frame
- Up to approximately 50 months
- description
- OS was defined as the time from randomization to death from any cause. K-M method was used to estimate median OS. 95% CI for median was computed using the method of Brookmeyer and Crowley.
- measure
- Arm A vs Arm B: Overall Survival (OS)
- time Frame
- From randomization to death (up to approximately 50 months)
- description
- An AE is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
- measure
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
- time Frame
- Up to approximately 50 months
- description
- ECOG is a 6-point scale (0-5) used to assess participants functional status, where, 0= Fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory \& able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2= ambulatory \& capable of all self-care but unable to carry out any work activities. Up \& about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead.
- measure
- Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
- time Frame
- Baseline up to 50 months
- description
- DOR was defined as the time from the first occurrence of a documented objective response (OR) to PD or death from any cause, whichever occurred first, as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. K-M method was used to estimate median DOR. 95% CI for median was computed using the method of Brookmeyer and Crowley.
- measure
- Arm A vs Arm B: Duration of Response (DOR)
- time Frame
- Up to approximately 50 months
- description
- CBR was defined as the percentage of participants who experienced the best response of stable disease (SD) with a minimum duration of 6 months, a CR, or a PR, as assessed by investigator with use of RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 95% CI for rates were constructed using the Clopper-Pearson method. Percentages are rounded off.
- measure
- Arm A vs Arm B: Clinical Benefit Rate (CBR)
- time Frame
- Up to approximately 50 months
- description
- DCR was defined as the percentage of participants who experienced the best response of CR, or PR, or SD, as assessed by investigator according to RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 95% CI for rates were constructed using the Clopper-Pearson method. Percentages are rounded off.
- measure
- Arm A vs Arm B: Disease Control Rate (DCR)
- time Frame
- Up to approximately 50 months
Full study description
- brief Summary
- 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.
Source references
Source notices and limitations
Discovery and provenance
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- occurrences
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- the WARNINGS AND PRECAUTIONS describe adverse reactions observed with exposure to GAVRETO as a single agent in a randomized, open-label study, AcceleRET-Lung (NCT04222972), which enrolled 223 patients with RET-fusion positive locally advanced unresectable or metastatic NSCLC. RET Fusion-Positive Non-Small Cell Lung Cancer The sa
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- y relevant laboratory abnormalities in patients who received GAVRETO included increased phosphate (40%). Other Clinical Trials Experience AcceleRET-Lung trial (NCT04222972) In AcceleRET-Lung trial (NCT04222972), single agent GAVRETO (n=108) was compared to chemotherapy/immunotherapy (n=104) in patients with RET fusion-positive NS
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- patients who received GAVRETO included increased phosphate (40%). Other Clinical Trials Experience AcceleRET-Lung trial (NCT04222972) In AcceleRET-Lung trial (NCT04222972), single agent GAVRETO (n=108) was compared to chemotherapy/immunotherapy (n=104) in patients with RET fusion-positive NSCLC. Adverse reactions were infections
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Preserved source evidence · Not medical advice