A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) (AcceleRET-Lung)

JRCT ID: jRCT2031210657

Registered date:10/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: RET-fusion Non Small Cell Lung Cancer
• Date of first enrollment: 02/06/2022
• Target sample size: 226
• Countries of recruitment: Australia,Japan,Belgium,Japan,Denmark,Japan,Finland,Japan,France,Japan,Germany,Japan,Ireland,Japan,Italy,Japan,Republic of Korea,Japan,Netherlands,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,Spain,Japan,Sweden,Japan,Switzerland,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan,Costa Rica,Japan,Argentina,Japan,Belarus,Japan,Brazil,Japan,Canada,Japan,Israel,Japan,Mexico,Japan,New Zealand,Japan,Panama,Japan,Ukraine,Japan
• Study type: Interventional

Intervention(s)

Pralsetinib Hydrate: Pralsetinib Hydrate will be administered orally, once daily at a dose of 400 mg.

Control Intervention:
Platinum-based chemotherapy with or without pembrolizumab
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)

1. 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.

2. Squamous histology
Carboplatin or cisplatin / gemcitabine
Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab

Outcome(s)

Primary Outcome

Efficacy
Progression Free Survival (PFS)

Secondary Outcome

Safety, Efficacy, Other
1. Overall Response Rate (ORR)
2. Overall Survival (OS)
3. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
4. Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS)Further characterising safety and tolerability.
5. Duration of Response (DOR)
6. Clinical Benefit Rate (CBR)
7. Disease Control Rate (DCR)
8. European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-C30 Questionnaires
9. European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-LC13 Scores

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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.

Related Information

• Primary Sponsor: Ahmadur Rahman
• Secondary ID(s): NCT04222972