Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Lung Diseases

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Respiratory Tract Diseases

Thoracic Neoplasms

Respiratory Tract Neoplasms

Bronchial Neoplasms

Carcinoma, Bronchogenic

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Bronchial Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

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Vitamins

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Carboplatin

Osimertinib

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Folinic Acid

Folate

Vitamin B9

Tyrosine

Phase 1 dose escalation of BLU-701 as monotherapy at various dose levels

BLU-701 in combination with osimertinib 40 mg or 80 mg tablets for oral administration

BLU-701 in combination with platinum-based chemotherapy (carboplatin and pemetrexed):

Carboplatin - IV infusion dosed to target AUC of 5-6 mg/mL min q3w

Pemetrexed - IV infusion dosed to 500 mg/m2 q3w

Phase 2 expansion group for BLU-701 as monotherapy at a dose determined during Part 1A in patients harboring the EGFR C797X resistance mutation

BLU-701

Osimertinib tablets for oral administration

osimertinib

carboplatin

pemetrexed

This is a Phase 1/2, open-label, first-in-human (FIH) study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of BLU-701 as monotherapy or in combination with either osimertinib or platinum-based chemotherapy in patients with EGFRm NSCLC.

The study was planned to include an initial Phase 1 portion to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-701 as monotherapy (Part 1A; initially in a once daily (QD) regimen with the option to evaluate twice daily (BID) dosing if supported by emerging PK and safety data), as well as additional dose-escalation portions to determine the RP2D of BLU-701 in combination with osimertinib (Part 1B) or in combination with carboplatin and pemetrexed (Part 1C). A Phase 2 part was planned to further evaluate the efficacy and safety of BLU-701 as monotherapy at RP2D (Part 2A). Phase 1 Part 1 A was initiated; however, the study was terminated prior to establishing BLU-701 MTD and/or RP2D.

(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC

A Phase 1/2 Study of the Highly Selective EGFR Inhibitor, BLU-701, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer

MTD determination: dose limiting toxicity (DLT) rate

RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and antitumor activity data

ORR - the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1

ORR - the proportion of patients who experience a best response of confirmed complete response (CR) or partial response (PR) according to RECIST 1.1

DOR - time from first documented response of CR or PR to the date of first documented progressive disease or death due to any cause, whichever occurs first

maximum plasma drug concentration (Cmax) time to maximum plasma drug concentration (Tmax) time of last quantifiable plasma drug concentration (Tlast) area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-24 for QD and AUC0-12 for BID) trough concentration (Ctrough) apparent volume of distribution (Vz/F) terminal elimination half-life (t½) apparent oral clearance(CL/F) accumulation ratio (R)

dual specificity phosphatase (DUSP6)

sprouty RTK signaling antagonist 4 (SPRY4)

DCR - proportion of patients who experience a best response of CR, PR, or SD according to RECIST 1.1

CBR - proportion of patients who experience a confirmed CR or PR, or SD with a duration of at least 16 weeks according to RECIST 1.1

PFS - time from the first dose of BLU-701 until the date of first documented PD or death due to any cause

OS - time from the first dose of BLU-701 until the date of death due to any cause

CNS-ORR - proportion of patients with measurable (target) intracranial metastases at baseline who experience a confirmed intracranial CR or PR according to RECIST 1.1 principles

CNS-DOR - time from first documented intracranial CR or PR to the date of first documented intracranial PD

CNS progression rate - proportion of patients with CNS progression as a component of first disease progression on study

ECG parameters extracted from continuous 12-lead Holter recordings

Blueprint Medicines Corporation

Etoposide

Cisplatin

Durvalumab

Etoposide phosphate

Alectinib

Gefitinib

Necitumumab

Antineoplastic Agents, Immunological

The patients in this group will receive osimertinib taken in combination with savolitinib

The patients in this group will receive osimertinib taken in combination with gefitinib

The patients in this group will receive osimertinib taken in combination with necitumumab

The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.

Patients in this group will not receive study treatment but receive further anticancer care (Standard of Care therapy or other experimental therapies) or supportive care, as clinically indicated, in accordance with local practice.

With Group C, the aim is to understand the clinical course and/or outcome for the overall clinical population after progression on first-line monotherapy with osimertinib.

The patients in this group will receive osimertinib taken in combination with alectinib

The patients in this group will receive osimertinib taken in combination with selpercatinib

The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab.

The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).

The patients in this group will receive osimertinib taken in combination with selumetinib

The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.

Osimertinib given orally at 80 mg once daily

Savolitinib will be given orally at 300 mg or 600mg once daily

Savolitinib

Gefitinib given orally at 250 mg once daily

Necitumumab given IV at 800 mg on Day 1 and Day 8 of every 3-week cycle

Durvalumab given IV at 1500 mg on Day 1 of every cycle

Carboplatin given IV on Day 1 of every 21-day cycle for up to 6 cycles

Pemetrexed given IV at 500 mg/m2 body BSA on Day 1 of every cycle

Alectinib given orally at 600mg twice daily and for Japanese patients at 300mg twice daily.

Selpercatinib given orally at 160mg twice daily

Selpercatinib

Selumetinib given orally at 75 mg twice daily for 4 days, followed by 3 days off treatment

Selumetinib

Etoposide 80-100 mg/m2 given IV on day 1, 2 and 3 of every 21-day cycle for up to 4 cycles.

Cisplatin 75-80 mg/m2 given IV on days 1 of each cycle

Datopotamab deruxtecan given IV at 4 or 6 mg/kg on Day 1 of every 3-week cycle.

Datopotamab deruxtecan

Helena A Yu, MD

Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

This is an open-label, multicentre, multi-drug, biomarker-directed Phase 2 platform study in patients with advanced non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation whose disease has progressed on first-line monotherapy with osimertinib.Treatment options for these patients are limited. Novel treatments for these patients are urgently required.

This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

Phase 2 platform study in patients with advanced Non-Small Lung Cancer harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation with evidence of radiological progression following first-Line osimertinib therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments. The study will be conducted in three groups (Groups A, B and C). Patient allocation to a study treatment within each group will be based on tumour molecular profile. Biomarker positive patients or patients with histologically identifiable neuroendocrine transformation to small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (NEC) will be allocated to a biomarker-matched study treatment in Group A, patients without a biomarker will be allocated to a study treatment in Group B and patients with a biomarker amenable to therapies not currently available in ORCHARD will be allocated to Group C.

Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)

A Biomarker-directed Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

The percentage of patients with a confirmed investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression). Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST (Response Evaluation Criteria In Solid Tumours)1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from the date of first response until date of disease progression or death in the absence of disease progression. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from the date of the first dose of study treatment until death due to any cause.

Blood samples will be collected at various timepoints to evaluate the sparse pharmacokinetics of study therapeutic agents.

Blood samples will be collected at various timepoints to evaluate the serial pharmacokinetics of study therapeutic agents

To evaluate safety and tolerability of each study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC	NCT05153408	Lung Neoplasm Carcinoma, Non-... Respiratory Tra... Neoplasms Neoplasms by Si... Lung Diseases Respiratory Tra... Carcinoma, Bron... Bronchial Neopl... Adenocarcinoma Carcinoma Neoplasms by Hi... Neoplasms, Nerv... EGFR C797S EGFR C797A EGFR L858R EGFR Exon 19 De... EGFR Gene Mutat... EGF-R Positive ... EGFR Mutation R... EGFR Activating... Thoracic Neopla... Antineoplastic ... Protein Kinase ... EGFR C797G EGFR C797X Non Small Cell ...	BLU-701 osimertinib carboplatin pemetrexed	18 Years -	Blueprint Medicines Corporation
Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)	NCT03944772	Non-Small Cell ...	Osimertinib Savolitinib Gefitinib Necitumumab Durvalumab Carboplatin Pemetrexed Alectinib Selpercatinib Selumetinib Etoposide Cisplatin Datopotamab der...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for egfr c797x

Every month we try and update this database with for egfr c797x cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for egfr c797x

Every month we try and update this database with for egfr c797x cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for egfr c797x cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.