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 Lero is well tolerated; no lero-related SAEs have been reported, and no patient has withdrawn due to an AE.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
3345 - Escalation plans and DNACPR discussions in the unwell oncology patient
Presenter: Raghad Elghadi
Session: Poster Display session 1
Resources:
Abstract
4165 - The Relation between the Symptom Burden of Hospitalized Patients with Incurable Cancer and the Quality-of-Life of Their Family Caregivers
Presenter: Eman Tawfik
Session: Poster Display session 1
Resources:
Abstract
1784 - Clinical predictors for analgesic response to radiotherapy in patients with painful bone metastases
Presenter: Ragnhild Habberstad
Session: Poster Display session 1
Resources:
Abstract
5323 - 30-Day Mortality in Palliative Radiotherapy
Presenter: Shing Fung Lee
Session: Poster Display session 1
Resources:
Abstract
3942 - The relationship between Naldemedine administration and the maximum dose of oral opioids
Presenter: Shinya Kajiura
Session: Poster Display session 1
Resources:
Abstract
3698 - Exposure to low energy amplitude modulated radiofrequency electromagnetic fields (EMF) is associated with rapid improvement in quality of life (QoL) status in patients with advanced hepatocellular carcinoma (HCC), using various analyses of EORTC-C30.
Presenter: Elizabeth Santana
Session: Poster Display session 1
Resources:
Abstract
3885 - Olanzapine Combined with 5-HT3 RA Plus Dexamethasone for Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in High and Moderate Emetogenic Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Presenter: Jian-Guo Zhou
Session: Poster Display session 1
Resources:
Abstract
5700 - Early Palliative care in advanced cancer, is it really effective?
Presenter: Raquel Gómez Bravo
Session: Poster Display session 1
Resources:
Abstract
5924 - Deprescribing Potentially Inappropriate Medication in Cancer Patients
Presenter: Simon Reuter
Session: Poster Display session 1
Resources:
Abstract
5314 - Spirituality and religious coping for Cancer patients and providers: An ‘Almighty’ belief for palliative care
Presenter: Vibhay Pareek
Session: Poster Display session 1
Resources:
Abstract