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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

Spots Global Cancer Trial Database for egfr mutant nsclc