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

Roche

Status and phase: Active, not recruiting; Phase 3

Conditions: Neoplasms by Site; Neoplasms, Nerve Tissue; Carcinoma; Head and Neck Neoplasms; Lung Neoplasm; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; RET-fusion Non Small Cell Lung Cancer; Respiratory Tract Neoplasms; Neoplasms by Histologic Type; Carcinoma, Bronchogenic; Thoracic Neoplasms; Lung Diseases; Neoplasms; Carcinoma, Non-Small-Cell Lung; Bronchial Diseases; Respiratory Tract Disease

Treatments: Drug: Carboplatin; Drug: Nab-Paclitaxel; Drug: Paclitaxel; Drug: Gemcitabine; Drug: Pralsetinib; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT04222972

2023-505035-12-00 (Other Identifier)

BO42864

BLU-667-2303 (Registry Identifier)

2019-002463-10 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 223 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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223 participants in 2 patient groups

Pralsetinib

Experimental group

Description:

Participants randomized to the Experimental Arm will receive Pralsetinib

Treatment:

Drug: Pralsetinib

Platinum-based chemotherapy with or without pembrolizumab

Active Comparator group

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

Treatment:

Drug: Pemetrexed

Drug: Cisplatin

Drug: Pembrolizumab

Drug: Paclitaxel

Drug: Gemcitabine

Drug: Nab-Paclitaxel

Drug: Carboplatin