CHICAGO, June 4, 2018 /PRNewswire/ --
Not intended for US, Canada and UK-based media
- Two-year follow-up data on meaningful durable response, overall survival (OS) and progression-free survival (PFS) to be presented in patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive type of skin cancer
Merck and Pfizer today announced that updated efficacy and safety data from the pivotal JAVELIN Merkel 200 trial of BAVENCIO(R) (avelumab) in patients with metastatic Merkel cell carcinoma (mMCC), will be presented as an oral abstract session at the 54th American Society of Clinical Oncology (ASCO) Annual Meeting on Monday, June 4 from 10:12-10:24 a.m. CDT in Chicago, IL. At this two year follow-up update of the pivotal study, BAVENCIO continues to demonstrate clinically meaningful durable responses and stable rates of progression-free survival (PFS) and overall survival (OS) from previous analyses in patients who responded to this treatment. Clinical activity was observed across all patient subgroups, irrespective of PD-L1 expression in tumor tissue or Merkel cell polyomavirus status. The safety profile for BAVENCIO in this trial has not changed with longer follow-up and remains consistent with that observed in the overall JAVELIN clinical development program.
"These efficacy and safety results build upon the data that supported our FDA approval, " said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the Biopharma business of Merck. "Alongside our other data at ASCO, this two-year analysis is a significant advance in our understanding of the utility of BAVENCIO in MCC patients."
In JAVELIN Merkel 200 - an open-label, single-arm Phase II study - patients with histologically confirmed mMCC whose disease had progressed on or after chemotherapy administrated for distant metastatic disease received BAVENCIO 10 mg/kg intravenously every two weeks until disease progression or unacceptable toxicity. Eighty-eight patients were followed for a median of 29.2 months (range 24.8-38.1 months). The confirmed overall response rate (ORR) of 33% (95% confidence interval [CI] 23.3-43.8; complete response in 11.4%) remained unchanged from previous analyses reported at both one year and 18 months. Responses remained ongoing in 19 of 29 patients who responded to treatment, including 12 patients whose duration of response exceeded two years. Durable responses led to stable rates of PFS (29% at 12 months, 29% at 18 months and 26% at 24 months). Median OS was 12.6 months (95% CI 7.5-17.1) and the two-year OS rate was 36% (50% at 12 months and 39% at 18 months). With a minimum follow-up of two years, no new safety signals were identified for BAVENCIO and was consistent with prior reports. Sixty-seven patients (76.1%) had a treatment related adverse event (TRAE), 10 patients (11.4%) had a Grade 3 or less TRAE and 20 patients (22.7%) had an immune-related adverse event. No treatment-related deaths occurred.
"These results represent a key milestone for patients with mMCC, as chemotherapy has historically been the only treatment option for this devastating disease," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "These data, alongside the additional real-world data which are also being presented at ASCO, strengthen our confidence in BAVENCIO as a treatment option for this rare and aggressive skin cancer."
In addition to these updated JAVELIN Merkel 200 data, results from a global expanded access program for BAVENCIO as a second-line treatment for patients with mMCC will be presented. These data will be presented during a poster session on Monday, June 4 from 1:15-4:45 p.m. CDT.
The alliance's JAVELIN clinical development program involves at least 30 clinical programs, including seven Phase III trials, and nearly 8,300 patients across more than 15 tumor types.
| BAVENCIO(R) | (avelumab) | was | first | approved | in | the | US | in | 2017 | by | the | US | Food | and | Drug | Administration | (FDA) | for | the | treatment | of | adults | and | pediatric | patients | 12 | years | and | older | with | metastatic | Merkel | cell | carcinoma | (mMCC). | In | addition | to | the | FDA | accelerated | approval | in | mMCC, | avelumab | is | also | approved | in | the | US | under | accelerated | approval | for | the | treatment | of | patients | with | locally | advanced | or | metastatic | urothelial | carcinoma | (UC) | who | have | disease | progression | during | or | following | platinum-containing | chemotherapy, | or | who | 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 |
About JAVELIN Merkel 200
JAVELIN Merkel 200 is an international, multicenter, open-label, single-arm Phase II study of BAVENCIO conducted in 88 patients with metastatic MCC. Patients in this study were generally elderly (median age was 72.5 years, range 33-88 years) and pre-treated, with at least one line of chemotherapy (one [59.1%], two [29.5%] or three or more [11.4%] previous treatments). Patients received BAVENCIO 10 mg/kg intravenously once every two weeks. The protocol-defined analysis set for efficacy and safety consisted of all patients who received at least one dose of study treatment. The cut-off date for the planned primary analysis was six months after start of study treatment of the last patient. The primary endpoint of the study was confirmed best overall response according to RECIST v1.1 and assessed by an independent review committee. Secondary endpoints were duration of response, PFS, OS, response status by RECIST at six and 12 months, safety and tolerability, pharmacokinetics, and immunogenicity of BAVENCIO.
About Avelumab
Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.[2] -[4] Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.[4]-[6] In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.
Approved Indications in the US
The FDA granted accelerated approval for avelumab (BAVENCIO(R)) 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.
Important Safety Information from the US FDA Approval Label
The warnings and precautions for BAVENCIO include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.
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