The CLASSICAL-Lung trial (NCT03268057) is being conducted in collaboration with Merck KGaA, Darmstadt, Germany. It 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. Avelumab is co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc.
The design of the trial included 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. Results included 21 evaluable patients who were immunotherapy naïve and 32 patients whose disease was refractory or relapsed during prior treatment with immune checkpoint inhibitors (predominantly anti-PD-1). The primary objective 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.
The combination of pepinemab and avelumab appears to be well-tolerated.
The data presented at AACR, which build upon results presented at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in November 2019, show that 81% of immunotherapy-naïve patients (17/21) have experienced disease control, either a partial response (5/21 patients) or stable disease (12/21 patients), in response to combination immunotherapy. Of these, four patients have achieved a durable clinical benefit of greater than one year, and six have achieved a durable clinical benefit of greater than 6 months. Notably, in the cohort of evaluable patients whose tumors had progressed during or following treatment with anti-PD-x antibodies, 59% (17/29) benefited from switching to the combination therapy, suggesting that adding pepinemab to an immunotherapy treatment regimen has the potential to halt or reverse tumor progression.
“We continue to be encouraged by data from the CLASSICAL-Lung trial and are pleased to see preliminary signals suggesting durable responses,” said Dr. Maurice Zauderer, President and CEO of Vaccinex. “The combination of pepinemab and avelumab has potential to halt or reverse tumor progression, both in immunotherapy-naïve patients and those for whom prior single-agent immunotherapy treatments have failed. We look forward to continuing to advance pepinemab in additional cancer indications.”
For phase 2 and 3 for major stocks, give comparative data from trials of similar competing drugs. For phase 3, give data from phase 2 trial.
Pepinemab, also known as VX15/2503, is a humanized monoclonal antibody that binds and blocks the activity of semaphorin 4D (SEMA4D) which is an extracellular signaling molecule that regulates the migration and function of immune and inflammatory cells. Preclinical studies have demonstrated that the biological activities associated with antibody blockade of SEMA4D promote immune cell infiltration into tumors and prevent neurological damage in neuroinflammatory and neurodegenerative disease models. Vaccinex is focused on the development of pepinemab for the treatment of cancer and neurodegenerative diseases including Huntington’s disease.
Avelumab Approved Indications
Avelumab (BAVENCIO®) in combination with axitinib is indicated in the US, EU, Japan and other countries for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
The US Food and Drug Administration (FDA) also granted accelerated approval for avelumab (BAVENCIO®) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
Avelumab is currently approved for patients with mMCC in 50 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® monotherapy 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 treated with BAVENCIO® monotherapy include hyponatremia, lymphopenia, GGT increased; in patients receiving BAVENCIO® in combination with axitinib, grade 3-4 clinical chemistry and hematology laboratory value abnormalities included blood triglyceride increased and lipase increased.