Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Adenocarcinoma

Lung Diseases

Head and Neck Neoplasms

Neoplasms, Germ Cell and Embryonal

Respiratory Tract Diseases

Thoracic Neoplasms

Respiratory Tract Neoplasms

Carcinoma, Bronchogenic

Neoplasms, Nerve Tissue

Bronchial Diseases

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Amino Acids

Vitamins

Gemcitabine

Paclitaxel

Carboplatin

Pemetrexed

Pembrolizumab

Albumin-Bound Paclitaxel

Cisplatin

Pralsetinib

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tyrosine

Folinic Acid

Folate

Vitamin B9

Participants randomized to the Experimental Arm will receive Pralsetinib

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

Nab-Paclitaxel

Clinical Trials

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.

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

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

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Defined as the time from randomisation date to the first documented progressive disease (PD), as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurs first.

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 investigator according to RECIST 1.1.

Defined as the time from randomisation date to death due to any cause.

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).

Further characterising safety and tolerability.

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 investigator according to RECIST v1.1.

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 investigator according to RECIST v1.1.

Defined as the proportion of participants who experience a best response of CR, or PR, or SD, as assessed by investigator according to RECIST v1.1.

Hoffmann-La Roche

Digestive System Diseases

Gland and Hormone Related Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Carcinoma, Neuroendocrine

Colorectal Neoplasms

Thyroid Neoplasms

Thyroid Cancer, Papillary

Thyroid Diseases

Intestinal Diseases

Colonic Diseases

Colonic Neoplasms

Gastrointestinal Diseases

Neuroendocrine Tumors

Gastrointestinal Neoplasms

Intestinal Neoplasms

Endocrine Gland Neoplasms

Protein-Energy Malnutrition

Digestive System Neoplasms

Endocrine System Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Adenocarcinoma, Papillary

Rectal Diseases

Neoplasms, Neuroepithelial

Papillary Thyroid Carcinoma

Neuroendocrine Tumor

Thyroid Cancer, Medullary

Neuroepithelioma

Multiple doses of pralsetinib (BLU-667) for oral administration.

Oral dose of pralsetinib (BLU-667) as determined during Dose Escalation.

pralsetinib (BLU-667) is a potent and selective inhibitor of the RET mutations, fusions, and predicted resistant mutants

pralsetinib (BLU-667)

This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.

The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Both parts will enroll participants with advanced non-resectable NSCLC, advanced non-resectable thyroid cancer and other advanced solid tumors that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or the participants must be intolerant to or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease.

Phase 1 (Complete):

* Advanced MTC, NSCLC or other solid tumor
* 30-600mg (PO QD or BID)

Phase 2 (400mg QD):

* Group 1: RET fusion NSCLC previously treated with a platinum chemotherapy
* Group 2: RET fusion NSCLC not previously treated for metastatic disease
* Group 3: MTC previously treated with cabozantinib and/or vandetanib
* Group 4: MTC not previously treated with cabozantinib or vandetanib
* Group 5: Other solid tumors with a RET fusion not eligible for any of the other groups and previously treated with SOC or have no acceptable SOC for their tumor type as determined by the investigator
* Group 6: Any solid tumor with a RET alteration (fusion or mutation) previously treated with a selective RET Inhibitor
* Group 7: Other solid tumors with a RET mutation previously treated with SOC
* Group 8: RET fusion NSCLC previously treated with a platinum chemotherapy (China only)
* Group 9: MTC not previously treated with systemic therapy for advanced or metastatic disease (China only)

Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

A Phase 1/2 Study of the Highly-selective RET Inhibitor, BLU-667, in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors

As assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO), as appropriate per tumor type

As assessed by RECIST v1.1 or RANO, as appropriate per tumor type

Clinical Benefit Rate (CBR), Duration of Response (DOR), Disease Control Rate (DCR), Progression Free Survival (PFS)

RET gene status (i.e. gene fusion partner or primary mutation and, for MTC, whether hereditary or sporadic)

Will be measured from lead II and will be corrected for heart rate (QTc)n using Fridericia's correction factors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)	NCT04222972	RET-fusion Non ... Lung Neoplasm Carcinoma, Non-... Respiratory Tra... Thoracic Neopla... Neoplasms by Si... Neoplasms Lung Diseases Respiratory Tra... Carcinoma, Bron... Bronchial Disea... Head and Neck N... Adenocarcinoma Carcinoma Neoplasms by Hi... Neoplasms, Germ... Neoplasms, Nerv...	Pralsetinib Carboplatin Cisplatin Pemetrexed Pembrolizumab Gemcitabine Paclitaxel Nab-Paclitaxel	18 Years -	Hoffmann-La Roche
Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors	NCT03037385	RET-altered Non... Medullary Thyro... RET-altered Pap... RET-altered Col... RET-altered Sol... Lung Neoplasm Carcinoma, Non-... Thyroid Disease... Thyroid Neoplas... Thyroid Cancer,... Carcinoma, Neur... Respiratory Tra... Thoracic Neopla... Neoplasms by Si... Neoplasms Lung Diseases Respiratory Tra... Carcinoma, Bron... Bronchial Neopl... Endocrine Syste... Endocrine Gland... Head and Neck N... Adenocarcinoma,... Adenocarcinoma Carcinoma Neoplasms, Glan... Neoplasms by Hi... Neuroendocrine ... Neuroectodermal... Neoplasms, Germ... Neoplasms, Nerv... Colonic Neoplas... Colorectal Neop... Intestinal Neop... Gastrointestina... Digestive Syste... Digestive Syste... Gastrointestina... Colonic Disease... Intestinal Dise...	pralsetinib (BL...	18 Years -	Hoffmann-La Roche

Spots Global Cancer Trial Database for lung cancer mutation