Clinical Trials

Date: 2017-06-05

Type of information: Presentation of results at a congress

phase: 1

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

Company: MabVax Therapeutics (USA - CA)

Product: [Zr-89]-HuMab-5B1 (MVT-5873)

Action mechanism:

• monoclonal antibody. MabVax's HuMab 5B1 antibody is fully human and was discovered from the immune response of cancer patients vaccinated with an antigen-specific vaccine during a Phase I trial at Memorial Sloan Kettering Cancer Center. In preclinical research, the 5B1 antibody has demonstrated high specificity and affinity, and has shown potent cancer cell killing capacity and efficacy in animal models of pancreatic, colon and small cell lung cancers. The antigen the antibody targets is expressed on more than 90% of pancreatic cancers making the antibody potentially broadly applicable to most patients suffering from this type of cancer.

Disease: pancreatic cancer - locally advanced or metastatic adenocarcinoma of the pancreas (PDAC) or other CA19-9 positive malignancies

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

• The recently completed Phase Ia trial was an open-label, dose-escalation study evaluating the safety, tolerability and pharmacokinetics of MVT-5873 as a single-agent in patients with locally advanced or metastatic pancreatic or colon cancer who had failed all prior therapies and regressed into progressive disease. Secondary endpoints included evaluation of tumor response by RECIST 1.1 and duration of response. A second arm of the Company's MVT-5873 Phase Ia trial is actively evaluating MVT-5873 in combination with gemcitabine plus nab-paclitaxel in newly diagnosed pancreatic cancer patients.(NCT02672917)

Latest news:

• • On June 5, 2017, MabVax Therapeutics reported results from its Phase I clinical trial of MVT-5873, being evaluated to treat patients with advanced pancreatic cancer and other CA19-9 positive cancers in a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 3, 2017. The Company highlighted that the single agent MVT-5837 appears safe and well tolerated in patients at biologically active doses. Further, all patients were evaluated by RECIST 1.1 for tumor response, and Mabvax reported one patient achieved a complete response and 11 more patients achieved stable disease in this dose escalation safety trial of 32 patients.
• Safe and Tolerable Dose Established: MVT-5873 was administered in both weekly and every other week dosing schedules. A maximum tolerated dose (MTD) was determined at 1 mg/kg with both dosing schedules. Dose limiting toxicities (DLTs) with single-agent MVT-5873 were reversible increases in liver function tests, that occurred early in Cycle 1 of therapy and typically resolved within a week. Most patients experiencing DLT events were able to continue therapy at a reduced dose. Infusion reactions were mitigated with the use of premedication and extended infusion times. To date, there has been no evidence that MVT-5873 induces antibody-drug-antibodies (ADA) in treated patients.
• Potential Efficacy Signal Observed in Patients: The levels of serum tumor marker CA19-9 are considered a valuable adjunct in the diagnosis, prognosis and monitoring of treatment of pancreatic cancer. Treatment with MVT-5873 normally results in a decrease in the serum tumor marker CA19-9 levels immediately following administration. After completing the first treatment Cycle, lasting 28 days, forty percent of patients had a sustained decrease in CA19-9 levels of greater than or equal to 50%. Patients with a greater than or equal to 50% reduction in CA19-9 levels continued treatment for a median of four cycles (range 2 to 9.75+), compared to one cycle (range 0.25 to 3) for patients with less than 50% decrease. Twelve of thirty-two patients achieved a stable disease response as determined by RECIST 1.1 measurements made every second cycle of therapy. One patient achieved a complete response by the first RECIST 1.1 time point at the end of the second cycle.
• • On December 5, 2016, MabVax Therapeutics announced the expansion of the Company's MVT-5873 phase I clinical trial to include the HonorHealth Research Institute located in Scottsdale, Arizona. HonorHealth Research Institute joins Memorial Sloan Kettering Cancer Center site in New York, and the Sarah Cannon Research Institute sites in Nashville, Tennessee and, Sarasota, Florida as phase I clinical trial sites for MabVax's fully human therapeutic antibody therapy. The lead investigator for the clinical trial at HonorHealth Research Institute is Erkut Borazanci, MD, MS.
• • On November, 14, 2016, MabVax Therapeutics reported on progress from its HuMab-5B1 antibody phase I program evaluating the use of MVT-5873 as a therapeutic antibody in patients with locally advanced and metastatic pancreatic cancer or other CA19-9 positive malignancies. The MVT-5873 phase I clinical trial initiated in February 2016 is designed to establish safety and determine the recommended phase II dose (RP2D) for MVT-5873 as both as monotherapy (Part 1 of the trial), and in combination with standard of care chemotherapy (Part 2) using nab-paclitaxel plus gemcitabine.  Initiation of Part 2 requires establishing three safe dose levels for MVT-5873 as monotherapy in patients with relapsed or refractory locally advanced or metastatic pancreatic cancer.  The company reports that the safety of MVT-5873 has been established at three incremental dose levels by treating 16 patients at three clinical sites.  While patients continue to be recruited to establish the RP2D, the Mabvax also reports that Part 2 of the clinical trial is now open and will include patients with previously untreated pancreatic cancer receiving a standard of care chemotherapy as defined in the protocol.
• To date, the study has consented 28 subjects with 3 in screening, 9 screen failures, and 16 subjects treated. Of the 16 patients treated, six continue to receive treatment. Patients can remain on therapy based on dose tolerability and investigator assessment of continued benefit including assessment of disease status using RECIST 1.1 criteria to evaluate tumor response rate and duration of response. Stable disease was noted for seven patients lasting from three months to eight months. The dosage safety levels established in Part 1 of the trial also support the dosage levels of MVT-5873 to be used in conjunction with the company's MVT-2163 immuno-PET imaging agent and the MVT-1075 radioimmunotherapy product which is planned to begin phase I clinical evaluation early in 2017.
• • On June 13, 2016, MabVax Therapeutics announced the initiation of a second investigational Phase I site for MVT-5873 (HuMab-5B1) with Sarah Cannon Research Institute through its network of research sites. In addition to the Sarah Cannon Research Institute at Tennessee Oncology site in Nashville, Tenn., patient enrollment in the Phase I trial is underway within Sarah Cannon Research Institute at Florida Cancer Specialists in Sarasota, Fla.
• • On June 7, 2016, Mabvax announced the initiation of patient enrollment at Memorial Sloan Kettering Cancer Center (MSK) in the Phase I clinical trial evaluating MVT-5873 (HuMab-5B1) as a therapeutic treatment for patients with locally advanced or metastatic adenocarcinoma of the pancreas (PDAC) or other CA19-9 positive malignancies.  This is the second investigational site in the Phase I trial with patient recruitment currently underway at the Sarah Cannon Research Institute in Nashville, TN.
• • On March 21, 2016, MabVax Therapeutics announced initiation of a phase I clinical trial of HuMab-5B1 for patients with locally advanced or metastatic adenocarcinoma of the pancreas (PDAC) or other CA19-9 positive malignancies. The CA19-9 target is expressed on more than 90% of pancreatic cancers and is a validated biomarker for the disease. The Company filed an Investigational New Drug (IND) application for this product on November 30, 2015 and received FDA authorization to proceed with the study on December 24, 2015.
• • On December 1, 2015, MabVax Therapeutics announced it has filed an Investigational New Drug Application (IND) with the FDA for its lead fully human antibody product HuMab 5B1 as a therapeutic agent. The planned Phase I trial will evaluate the safety, tolerability and pharmacokinetics of HuMab 5B1 as a single agent or in combination with the current standard of care chemotherapy regimen in subjects with metastatic pancreatic cancer. The first cohort of patients to be enrolled in the planned clinical trial will be enrolled in a traditional dose escalation regimen to assess safety and determine the optimal dose of the antibody. A second patient cohort will establish the safety and optimized dose of the antibody when administered with standard of care chemotherapy and a third patient cohort will be administered the optimized dose of antibody as a single agent for the treatment of patients with advanced cancer. MabVax plans to file a second IND application this month for its HuMab 5B1-based PET imaging agent and, subject to FDA acceptance, will begin this Phase I trial as early as possible in 2016. When the antibody is combined with a radio-label as a novel PET imaging agent, the 89Zr-HuMab 5B1 product has demonstrated high image resolution of tumors in established xenograft animal models, making it attractive as a potential companion diagnostic for the HuMab 5B1 therapeutic product.

 

Is general: Yes