On September 6, 2018 Checkpoint Therapeutics, Inc. ("Checkpoint") (NASDAQ: CKPT), a clinical-stage immuno-oncology biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for patients with solid tumor cancers, reported positive preliminary safety and efficacy data from an ongoing Phase 1/2 clinical trial of CK-101 (also known as RX518), a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being evaluated in advanced non-small cell lung cancer (NSCLC) (Press release, Checkpoint Therapeutics, SEP 6, 2018, View Source [SID1234529736]). The data will be presented on Monday, Sept. 24, at 10:30 a.m. ET in a late-breaking oral presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer in Toronto.
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"These preliminary data demonstrate CK-101 is well-tolerated at the doses tested while also demonstrating encouraging anti-tumor activity, particularly in treatment-naïve EGFR mutation-positive lung cancer patients," said Melissa L. Johnson, M.D., Associate Director, Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, PLLC, and study chair of the Phase 1/2 trial.
"The data to date demonstrate CK-101’s potential to be a highly effective mutant-selective EGFR inhibitor with the potential for a differentiated safety profile," said James F. Oliviero, President and Chief Executive Officer of Checkpoint Therapeutics. "We look forward to continuing to advance CK-101 towards a pivotal Phase 3 trial next year, positioning CK-101 to potentially be only the second third-generation EGFR inhibitor to enter the market."
The first-in-human, multicenter trial is evaluating CK-101 in NSCLC patients with EGFR mutations and other advanced malignancies (NCT02926768). Following dose escalation ranging from 100 mg to 1,200 mg/day in patients with any solid tumor where targeted EGFR was deemed reasonable, a first doseexpansion cohort was enrolled at 400 mg twice daily in patients with a confirmed diagnosis of either (1) EGFR mutation-positive advanced or metastatic NSCLC without prior exposure to EGFR-TKI therapy, or (2) T790M-positive advanced or metastatic NSCLC with disease progression on previous EGFR-TKI therapy. There was no limit on the number of prior lines of systemic therapy patients received prior to entering the study.
Key Data from the Abstract
As of June 2018, 37 patients had been treated with CK-101 in dose escalation and dose-expansion cohorts
and were evaluable for safety.
• No dose limiting toxicities (DLTs) or treatment
• The most common drug-related treatment-emergent adverse events (>10%) included nausea
(16%), diarrhea (14%), lacrimation increased (14%) and vomiting (11%).
In dose-expansion, 19 EGFR mutation-positive NSCLC patients were treated with CK-101 at a dose of 400
mg twice daily and were evaluable for response (RECIST v1.1). Eight patients achieved a partial response
(7 confirmed, 1 pending). Additional efficacy findings include:
• In eight treatment-naïve patients, six patients (75%) achieved a partial response.
• In six patients with brain metastases present at baseline, three patients achieved a partial
response.
• Higher drug exposures were associated with a higher response rate with a confirmed objective
response rate (ORR) of 55% (6/11) in patients achieving a maximum serum concentration (Cmax)
greater than 400 ng/mL.
• 100% (19/19) disease control rate was observed, with 84% (16/19) of patients experiencing target
lesion reduction versus baseline.
• Median duration of response and progression-free survival were not reached as of the data cutoff.
Enrollment in the trial is ongoing to identify the optimal dose to maximize therapeutic effect.
Oral Presentation
Details of the oral presentation at the IASLC 19th World Conference on Lung Cancer are as follows:
Title: CK-101 (RX518), a Third Generation Mutant-Selective Inhibitor of EGFR in NSCLC: Results of
an Ongoing Phase I/II Trial
Date / Time: Monday, Sept. 24, 2018 at 10:30am
Session: Novel Therapies in ROS1, HER2 and EGFR
Presenter: Melissa L. Johnson, M.D., Associate Director, Lung Cancer Research, Sarah Cannon
Research Institute at Tennessee Oncology, Nashville, Tenn.
The full abstract can be found on the conference website and is also available on the Publications page in
the Pipeline section of Checkpoint’s website, www.checkpointtx.com.
About CK-101
CK-101 (also known as RX518) is an oral, third-generation, irreversible kinase inhibitor against selective mutations in the EGFR gene. Activating mutations in the tyrosine kinase domain of EGFR, such as L858R and exon 19 deletion, are found in approximately 20 percent of patients with advanced non-small cell lung cancer (NSCLC).
Compared to chemotherapy, first-generation EGFR inhibitors significantly improved objective response rate and progression-free survival in previously untreated NSCLC patients carrying EGFR mutations. However, tumor progression could develop due to resistance mutations, often within months of treatment with first-generation EGFR inhibitors. The EGFR T790M "gatekeeper" mutation is the most common resistance mutation found in patients treated with first-generation EGFR inhibitors. The mutation decreases the affinity of first-generation inhibitors to EGFR kinase domain, rendering the drugs ineffective. Second-generation EGFR inhibitors have improved potency against the T790M mutation, but have not provided meaningful benefits in NSCLC patients due to toxicity from also inhibiting wild-type EGFR. Third-generation EGFR inhibitors are designed to be highly selective against both EGFR-TKIsensitizing and resistance mutations, with minimal activity on wild-type EGFR, thereby improving tolerability and safety profiles.
Checkpoint Therapeutics is developing CK-101 for the treatment of NSCLC patients carrying the susceptible EGFR mutations. These include the EGFR T790M mutation in second-line NSCLC patients, as well as the EGFR L858R and exon 19 deletion mutations in first-line NSCLC patients. Checkpoint holds an exclusive worldwide license (except with respect to certain Asian countries) to CK‐101, which it acquired from NeuPharma, Inc., in 2015.