A Phase 1/2 Study of BLU-451 in Advanced Cancers with EGFR Exon20 Insertion Mutations

NOT ENROLLING
Protocol # :
22-278
Conditions
Lung Neoplasm Malignant
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Disease
Carcinoma, Bronchogenic
Bronchial Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms by Histologic Type
EGFR Exon 20 Mutation
EGFR Exon 20 Insertion Mutation
EGFR Activating Mutation
Antineoplastic Agents
Metastatic Lung Cancer
Brain Metastases
EGFR-mutated NSCLC
EGFR Atypical Mutations, Including G719X and L861Q
Phase
I/II
Disease Sites
Lung
Principal Investigator
Janne, Pasi, A
Site Research Nurses
Becker, Simone
Callahan, Carragh
Callahan, Carragh
Hurley, Meaghan
Janell, Samantha
Kelley, Elaine
Kuberski, Heather, D.
Lam, Ethan
Mcnally, Megan
Souza, Joseph
Stober, Lisa, L.
Sullivan, Molly, O'Brien
Thistle, Katrina, M.
Wanat, Alexandra

Trial Description

This is a Phase 1/2, open-label first-in-human study of the safety, pharmacokinetics (PK),
pharmacodynamics, and anti-tumor activity of BLU-451 monotherapy and BLU-451 in combination
with platinum-based chemotherapy (carboplatin and pemetrexed). All participants will receive
BLU-451 on a 21-day treatment cycle.

Eligibility Requirements

INCLUSION CRITERIA:

All participants:

- Documented EGFR mutation, based on Next-generation sequencing (NGS) testing of tumor
or liquid biopsy analyzed in a local Clinical Laboratory Improvement Amendments (CLIA)
(or International Organization for Standardization (ISO) 15189)-certified or
equivalent laboratory are required. Redacted copies of laboratory results must be
available for Sponsor review.

- Able to provide a new or archived pretreatment formalin-fixed, paraffin-embedded
(FFPE) tumor sample. For participants who received EGFR-targeted therapy subsequent to
the most recent archived biopsy, all efforts should be made to obtain a new biopsy
unless it is not safe or feasible to obtain one.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

- Participants must be without seizures for at least 14 days prior to enrollment, and
patients who receive treatment with anti-epileptic drugs must be on stable doses for
at least 14 days prior to enrollment.

- Adequate hematological, renal, and hepatic function:

Participants in Phase 1

- Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per
American Joint Committee on Cancer (AJCC) 8th edition) or other metastatic cancers
except for primary CNS tumors (Part 1A or Part 2 only).

- Must have evaluable or measurable disease per RECIST v1.1.

- Progression on or after or intolerance to most recent systemic therapy.

Participants in Phase 2

- Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per AJCC
8th edition).

- Must have measurable disease by RECIST 1.1.

EXCLUSION CRITERIA:

- Have disease that is suitable for local therapy administered with curative intent.

- Have tumor that harbors known driver alterations (including, but not limited to ROS,
BRAF V600E, ALK, RET, HER2, MET, KRAS, NTRK1/2/3, EGFR C797X, or EGFR T790M mutation).
These criteria are not applicable to Phase 1 Part 1B.

- Have NSCLC with mixed cell histology or a tumor with known histologic transformation
(NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).

Other protocol-defined inclusion and exclusion criteria apply

22-278