Abstract 1613
Background
Lerociclib (lero) is a potent, selective oral CDK4/6 inhibitor (CDK4/6i). Preclinical and early clinical data have demonstrated that lero is differentiated based on its favorable safety/tolerability profile and ability to be dosed continuously with less dose-limiting neutropenia. Encouraging preliminary efficacy has been observed in HR+/HER2- breast cancer in combination with fulvestrant (NCT#02983071). Several putative mechanisms of resistance to EGFR TKIs are upstream of the CDK4/6 pathway, and in vitro and in vivo studies with CDK4/6i + EGFR TKIs have demonstrated enhanced efficacy and delayed time to resistance. These data provide strong rationale to investigate lero + osimertinib (osi) in the clinic.
Methods
Patients with metastatic NSCLC, confirmed EGFR mutation associated with EGFR TKI sensitivity, ECOG of 0 or 1, and treatment with ≤2 lines of chemo or any EGFR TKI including osi are eligible for this phase Ib study. Patients receive lero QD or BID continuously in combination with 80 mg osi QD until disease progression. The objectives are to evaluate DLTs, safety, tolerability, PK, and anti-tumor efficacy, and to determine the dose for the randomized phase II portion of the study.
Results
Currently, 18 patients (mean age 63 years) have been enrolled and received lero doses of 200, 300, or 400 mg QD; the longest duration being 317 days. BID enrollment is ongoing. Lero is well tolerated; no lero-related SAEs have been reported, and no patient has withdrawn due to an AE. One DLT of Grade 4 neutropenia occurred at 400 mg QD. The most common lero-related TEAEs are neutropenia and diarrhea. The incidence of diarrhea with lero + osi is similar to single agent osi (FLAURA study). There have been no reports of VTE, QT prolongation, or DILI. No clinically relevant drug-drug interaction has been observed.
Conclusions
The combination of continuously administered lero + osi in patients with EGFRmut NSCLC (treatment naïve or previously treated) is well tolerated with only one DLT event to date. Updated safety, anti-tumor efficacy, and cfDNA data will be presented (NCT#03455829).
Clinical trial identification
NCT03455829.
Editorial acknowledgement
Legal entity responsible for the study
G1 Therapeutics, Inc.
Funding
G1 Therapeutics.
Disclosure
D. Berz: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Genentech; Honoraria (self): AstraZeneca; Honoraria (self): Merck; Honoraria (self): Tempus; Honoraria (self): Biocept; Shareholder / Stockholder / Stock options, Major Owner: Valkyrie Therapeutics. A. Spira: Advisory / Consultancy: G1 Therapeutics. J.W. Goldman: Honoraria (self), Research grant / Funding (institution): AstraZeneca. Y.L. Pritchett: Full / Part-time employment: G1 Therapeutics. C.G. Cisneros: Full / Part-time employment: G1 Therapeutics. C. Li: Full / Part-time employment: G1 Therapeutics. J.A. Sorrentino: Full / Part-time employment: G1 Therapeutics. R. Malik: Full / Part-time employment: G1 Therapeutics. A.P. Beelen: Full / Part-time employment: G1 Therapeutics. All other authors have declared no conflicts of interest.
Resources from the same session
4883 - A New Population Model Validated Pharmacokinetic Similarity of HLX01 and Rituximab in B-Cell Lymphoma
Presenter: Yuankai Shi
Session: Poster Display session 1
Resources:
Abstract
4908 - Efficacy of salvage therapy in the treatment of Helicobacter pylori-positive gastric low-grade mucosa-associated lymphoid tissue lymphoma
Presenter: Sung-Nam Lim
Session: Poster Display session 1
Resources:
Abstract
2360 - Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing
Presenter: Seok Jae Huh
Session: Poster Display session 1
Resources:
Abstract
2430 - Clinical features, treatment and outcomes of colon and rectum mucosa-associated lymphoid tissue (MALT) lymphoma: Literature reviews published in English between 1993 and 2017
Presenter: Jeong Yeon Kim
Session: Poster Display session 1
Resources:
Abstract
4654 - Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 52 patients
Presenter: Guldane Cengiz Seval
Session: Poster Display session 1
Resources:
Abstract
1732 - Safety and efficacy of Bendamustine and Rituximab (BR) regimen in Indian Chronic Lymphocytic Leukemia patients
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
5784 - N-terminal B-type natriuretic peptide (NT-proBNP) as an independed prognostic marker for patients with newly diagnosed multiple myeloma complicated by dialysis-dependent renal failure
Presenter: Sergey Semochkin
Session: Poster Display session 1
Resources:
Abstract
836 - The first-line effect of Bortezomib-based Therapy on Clinical Outcomes for Taiwanese Patients with multiple myeloma
Presenter: Ching-Liang Ho
Session: Poster Display session 1
Resources:
Abstract
2085 - Impact of Donor Lymphocyte Infusion in Relapsing Myeloid Neoplasms Post Allogeneic Hematopoietic Stem Cell Transplantation
Presenter: Hanafy Hafez
Session: Poster Display session 1
Resources:
Abstract
6079 - Invasive fungal diseases in patients with Hodgkin’s lymphoma before and after allogeneic hematopoietic stem cell transplantation
Presenter: Marina Popova
Session: Poster Display session 1
Resources:
Abstract