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63% of evaluable subjects whose tumors had progressed during prior checkpoint inhibitor therapy benefited from treatment with the combination of pepinemab and avelumab
Primary completion anticipated in second half of 2019
This multi-center, open-label study is designed to evaluate the safety and potential efficacy of the combination of pepinemab and avelumab in patients with advanced NSCLC (n=62) who are either immunotherapy naïve or who failed prior immunotherapy with approved checkpoint inhibitors.
Interim results presented
He added, “We believe the study’s interim results, although early, are very encouraging, showing that the combination of our lead therapeutic candidate, pepinemab, together with avelumab checkpoint inhibitor, had promising anti-tumor activity in lung cancer patients who were either immunotherapy treatment naïve or had failed prior single agent anti-PD-1/PD-L1 immunotherapy. We were also very pleased to see signs of positive changes in the tumor microenvironment that may potentiate the effectiveness of checkpoint therapy. We believe this early data with a 63% positive response suggests synergy between our drug candidate and avelumab in potentially treating certain patients whose tumors progress on approved first or second line immunotherapies. We anticipate issuing another interim update later this year.”
Recap of Interim Results Presented at the
The CLASSICAL-Lung trial is a multi-center, open-label study designed to evaluate the safety and potential efficacy of the combination of pepinemab and avelumab in subjects with advanced NSCLC. The design of the trial consists of a 12-subject dose escalation phase to determine the recommended Phase 2 dose of pepinemab in combination with avelumab, followed by a 50-subject dose expansion phase. The primary objective of the dose expansion phase was to assess safety and tolerability. Secondary objectives include evaluation of efficacy, immunogenicity, and PK/PD. An exploratory objective is to identify candidate biomarkers of activity.
In the interim data presented at
Importantly, comparative analysis of available pre-treatment and on-treatment biopsies demonstrated increased CD8+ T cell influx into tumors and an increased ratio of T effector/T regulatory cells (Teff/Treg) following combination therapy, indicating a favorable treatment-related change in the tumor micro-environment. Tumor was absent or reduced in biopsies from the 2 subjects who had partial responses, and no tumor was evident in available biopsies from 3 of 4 subjects with stable disease.
No concerning safety signals with the combination of pepinemab and avelumab have been identified to date. One dose limiting toxicity (DLT), a grade 3 pulmonary embolism, occurred in the 10mg/kg pepinemab + 10mg/kg avelumab escalation cohort, this resolved and did not recur in that same subject or additional subjects in any cohort. In addition, there have been no dropouts or discontinuations due to toxicity.
Avelumab Approved Indications
Avelumab (BAVENCIO®) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
Avelumab is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
Avelumab Important Safety Information from the US FDA-Approved Label
The warnings and precautions for avelumab (BAVENCIO®) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions [which can be severe and have included fatal cases]), infusion-related reactions, hepatotoxicity, major adverse cardiovascular events (MACE) [which can be severe and have included fatal cases], and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO® include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO® in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 clinical chemistry and hematology laboratory value abnormalities reported in at least 10% of patients across studies include hyponatremia, lymphopenia, GGT increased, blood triglycerides increased and lipase increased.
For full Prescribing Information and Medication Guide for BAVENCIO®, please see www.BAVENCIO.com.
Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding
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Source: Vaccinex, Inc.