On June 5, 2017 Abbvie IMBRUVICA (ibrutinib) reduced cells that may play an important role in the survival and proliferation of chronic lymphocytic leukemia (CLL), without negatively impacting non-cancerous immune system cells, through one year of treatment, according to new data presented today at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (poster session: 8:00 a.m. – 11:30 a.m. CDT; abstract #7524).1 The data regarding IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, were announced by AbbVie (NYSE: ABBV), a global biopharmaceutical company. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

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The data, which assessed the impact of treatment on the immune system and changes in circulating cells, found that IMBRUVICA reduced cancerous cells and other cells of the immunosuppressive tumor microenvironment including CLL cells (90 percent), myeloid-derived suppressor cells (MDSC, 61 percent) and some T cells (27-52 percent). At the same time, IMBRUVICA spared non-cancerous immune system cells, including naïve T cells, T memory stem cells (TSCM) and natural killer (NK) cells through one year of treatment. Classical monocytes (a type of white blood cell) were increased by 187 percent, while non-classical monocytes and intermediate monocytes remained relatively steady. The data were derived from the Phase 3 RESONATE-2 trial (PCYC-1115), which found IMBRUVICA reduced the risk of progression or death of treatment-naïve patients with CLL compared to the traditional chemotherapeutic chlorambucil.1

"These results show the IMBRUVICA mechanism of action at work and provide greater clarity on the potential role that BTK inhibition plays in tumor modulation," said Danelle James, M.D., M.S., Head of Clinical Science, Pharmacyclics LLC, an AbbVie company. "These data suggest that treatment with the chemotherapy agent chlorambucil has broad effects when administered to CLL patients – where almost all subsets of normal immune cells are impacted or decreased. In contrast, treatment with ibrutinib resulted in preservation of certain important immune cell subsets, providing evidence that IMBRUVICA may offer a more targeted treatment approach."

The study found treatment with chlorambucil indiscriminately affected most immune cell subsets in circulation, including progressively reducing circulating B, T, NK, NKT cells, MDSC and monocytes by 69-99 percent. All development stages of CD4+ and CD8+ T cells, except TSCM, decreased by 51-90 percent. Regulatory T cells (Treg) and PD1+ T cells also decreased similarly; however, long-term activated T cells (TLA) were not impacted.1

"We’ve made substantial progress in cancer treatment over the years with the discovery and introduction of novel therapies such as IMBRUVICA. We are able to more specifically target the tumor while sparing normal immune cells, and the study data show the potential for improved treatment options that eliminate or minimize the use of chemotherapy in CLL," added James.

CLL is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The leukemia (cancer) cells start in the bone marrow but then spread into the blood. There are more than 20,000 newly diagnosed CLL patients every year.2 CLL is primarily a disease of the elderly, with a median age of 71 at diagnosis.3 To date, more than 25,000 CLL patients have been treated in the U.S. with IMBRUVICA since approval in 2014.

In the study over one year, immunophenotypic analyses were performed by flow cytometry on peripheral blood to assess lymphoid and myeloid cells of treatment-native CLL patients who received IMBRUVICA 420 mg once daily (n=50) or 0.5-0.8 mg/kg chlorambucil twice a month (n=30).1

About the RESONATE-2 Study

RESONATE-2 is a Pharmacyclics-sponsored, randomized, multi-center, open-label, Phase 3 study which enrolled 269 treatment-naïve patients with CLL/small lymphocytic leukemia (SLL) aged 65 years or older in the U.S., EU and other regions. Patients were randomized to receive either IMBRUVICA 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg. The study met its primary endpoint, demonstrating improved progression free survival (PFS), as assessed by an independent review committee (IRC).

The most common adverse events (AEs >20%) of all Grades in the RESONATE-2 trial for ibrutinib were diarrhea (42%), fatigue (30%), cough (22%) and nausea (22%); AEs for chlorambucil included nausea (39%), fatigue (38%), neutropenia (23%) and vomiting (20%). Hypertension occurred at a higher rate with ibrutinib (14%), including Grade 3 (4%) with no Grade 4 or 5 events. All six patients with Grade 3 hypertension were managed with hypertensive medication and did not require ibrutinib dose reduction or discontinuation. Atrial fibrillation occurred in eight patients (6%) in the ibrutinib arm and was primarily Grade 2 in six patients and Grade 3 in two patients. It was managed with discontinuation in two patients and without a dose modification in remaining patients.

Overall, AEs leading to treatment discontinuation were less frequent with ibrutinib than with chlorambucil (9% versus 23%). There were three deaths in the ibrutinib arm and 17 deaths in the chlorambucil arm over the median follow-up of 18.4 months. None of the patients who progressed on ibrutinib died during the subsequent follow-up period.

About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.3,4 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.4

IMBRUVICA is FDA-approved in five distinct patient populations: CLL, SLL, Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).4

IMBRUVICA was first approved for patients with MCL who have received at least one prior therapy in November 2013.
Soon after, IMBRUVICA was initially approved in CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
IMBRUVICA was approved for patients with WM in January 2015.
In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for CLL/SLL patients.
In January 2017, IMBRUVICA was approved for patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.4

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA has been granted four Breakthrough Therapy Designations from the FDA, spanning CLL/SLL, WM, MCL, and chronic graft-versus-host-disease (cGVHD). In addition, IMBRUVICA is the first standard therapy specifically approved for patients with previously-treated MZL and WM.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with approximately 130 ongoing clinical trials. There are a total of 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and approximately 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 70,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 13%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 3% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia** (61%), thrombocytopenia** (62%), diarrhea (43%), anemia** (41%), musculoskeletal pain (30%), rash (30%), nausea (29%), bruising (30%), fatigue (29%), hemorrhage (22%), and pyrexia (21%).

** Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MZL patients were pneumonia (10%), fatigue (6%), diarrhea (5%), rash (5%), and hypertension (5%).

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9% (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions. Most common adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash, and neutropenia (1% each) in CLL/SLL patients and subdural hematoma (1.8%) in MCL patients. The most common adverse reactions leading to discontinuation were interstitial lung disease, diarrhea, and rash (1.6% each) in WM and MZL patients.

DRUG INTERACTIONS

CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

Please see Full Prescribing Information: View Source

June 05, 2017 (GLOBE NEWSWIRE) — TG Therapeutics, Inc. (NASDAQ:TGTX), reported updated clinical data from its ongoing Phase I/Ib trial of TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody in combination with TGR-1202 (umbralisib), the Company’s oral, next generation PI3K delta inhibitor, and ibrutinib, a BTK inhibitor, in patients with Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin’s Lymphoma (NHL). Data from this trial was presented today during the 53rd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL. Additionally, a poster was presented describing the design of a study evaluating TGR-1202 in CLL patients who are intolerant to prior kinase inhibitor (KI) therapy, particularly ibrutinib and idelalisib.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "The triple data presented today provides a compelling case for combining our doublet, referred to as TG-1303, with ibrutinib across a number of b-cell malignancies for which ibrutinib is now approved. Importantly, the high rates of complete responses observed across these diseases with the triple therapy may enable some patients to discontinue treatment prior to becoming ibrutinib refractory, a population associated with very poor outcomes." Mr. Weiss continued, "Additionally, the data shown today strengthens our belief that TG-1303 is a safe and efficacious backbone upon which we can build triple and quad therapies, as we continue to strive towards identifying combinations that provide deeper remissions that can ideally avoid lifetime treatment. We look forward to further exploring multi-drug combination therapies both with currently approved agents as well as with our in-house pipeline products."

Highlights from today’s presentations include the following:

Poster Presentation: Tolerability and activity of chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib in patients with advanced CLL and NHL (Abstract #7511)

Poster Viewing & Discussion Details: Monday, June 5, 2017 8:00 AM-11:30 AM CT (Poster Viewing); 1:15 PM-2:30 PM CT (Poster Discussion)

This poster presentation includes data from patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) and Non-Hodgkin’s Lymphoma (NHL) treated with the triple combination of TGR-1202, TG-1101 and ibrutinib. All patients were relapsed or refractory to prior therapy, except 3 CLL patients who were treatment naïve. Three cohorts for each CLL/SLL and NHL were evaluated with TGR-1202 dose escalation starting with doses of 400 mg (cohort 1), followed by 600 mg (cohort 2) and 800 mg (cohort 3), in combination with TG-1101 at 900 mg and ibrutinib daily at 420 mg (CLL) and 560 mg (NHL).

Safety & Tolerability
Thirty Eight (38) patients were evaluable for safety (20 CLL/SLL patients, and 18 NHL patients). The triple combination appeared to be well tolerated in all patients, with neutropenia (32% all grades, 18% Grade 3/4) and pneumonia (18% all grades, 11% Grade 3/4), being the only Grade 3/4 AEs in > 10% of patients. Of the 38 patients treated to date, only two AEs (sepsis and pneumonia) led to treatment discontinuation. Median time on study was 11.1 months (range 0.4 – 30+ months) with 81% of patients on study > 6 months.

Clinical Activity
Clinical activity was observed at all dose levels with 36 of 38 patients evaluable for efficacy (19 CLL/SLL patients, and 17 NHL patients), with 2 patients having discontinued prior to first efficacy assessment (1 pneumonia, and 1 investigator discretion).

CLL/SLL Efficacy highlights include:

• 100% (19 of 19) Overall Response Rate (ORR), including a 32% Complete Response (CR) rate observed in patients with CLL/SLL (4 of 6 CR’s pending marrow confirmation)
• 50% of the CLL patients had a 17p and/or 11q deletion
• 3 CLL patients had prior BTK and/or PI3Kδ inhibitor therapy, including one patient refractory to both idelalisib and ibrutinib who attained a complete response (ongoing for 1.5+ years)

NHL Efficacy highlights include:

• Response Rates observed in patients with NHL:

100% (2 of 2) ORR, including one CR in patients with Marginal Zone Lymphoma (MZL)
100% (4 of 4) ORR, including 50% CR rate in patients with Mantle Cell Lymphoma (MCL)
80% (4 of 5) ORR, including 20% CR rate in patients with Follicular Lymphoma (FL)
17% (1 of 6) ORR in patients with Diffuse Large B-cell Lymphoma (DLBCL)
• FL patients were heavily pretreated including 2 with prior Autologous Stem Cell Transplant (ASCT), 1 refractory to prior ibrutinib, and 1 with 5 prior lines of rituximab based therapy
• DLBCL patients had a median of 4 prior therapies, and 4 of 6 were of non-GCB subtype

Poster Presentation: KI intolerance study: A phase 2 study to assess the safety and efficacy of TGR-1202 in pts with chronic lymphocytic leukemia (CLL) who are intolerant to prior BTK or PI3K-delta inhibitor therapy (Abstract: TPS7569)

This poster details the study design for an ongoing Phase II, multicenter, single-arm trial of TGR-1202 (umbralisib) in CLL patients requiring therapy who are intolerant to prior Kinase Inhibitor (KI) therapy. The study will enroll approximately 50 patients who have discontinued prior therapy with a BTK or PI3K delta inhibitor due to intolerance and not disease progression. The primary objective of the study is to determine the progression free survival (PFS) of TGR-1202 in this patient population. Key secondary objectives such as overall response rate, duration of response, time to treatment failure and safety of TGR-1202 as compared to the prior KI therapy will also be evaluated.

PRESENTATION DETAILS:

The above referenced presentations are now available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 5, 2017 MabVax Therapeutics Holdings, Inc. (Nasdaq: MBVX), a clinical-stage biotechnology company with a fully human antibody discovery platform focused on the rapid translation into clinical development of products to address unmet medical needs in the treatment of cancer, reported results from its Phase I clinical trial of MabVax’s therapeutic antibody 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) (Free ASCO Whitepaper) Annual Meeting on June 3, 2017 (Press release, MabVax, JUN 5, 2017, View Source [SID1234519443]). 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 the Company reported one patient achieved a complete response and 11 more patients achieved stable disease in this dose escalation safety trial of 32 patients.

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"The results of our Phase Ia trial with MVT-5873 indicate that we have a fully-human antibody targeting CA19-9 cancers that can be administered at doses with acceptable safety and with a potentially positive impact on disease. CA19-9 is broadly expressed in various cancers including pancreatic, colon, and small cell lung cancer making this antibody potentially useful for a larger patient population. The early efficacy signals from an identifiable subset of subjects has enabled us to understand those patients most likely to respond to MVT-5873 based therapy. At the maximum tolerated dose (MTD) we have established in this trial, we have demonstrated an acceptable safety margin and have cleared the way for MVT-5873 in combination with our immunoPET imaging agent (MVT-2163) and Radioimmunotherapy (MVT-1075) which are currently in phase I clinical trials," said David Hansen, President and CEO of MabVax.

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. Dr. Eileen O’Reilly, Associate Director of the David M. Rubenstein Center for Pancreatic Cancer Research, attending physician, member at Memorial Sloan Kettering Cancer Center and Professor of Medicine at Weill Cornell Medical College is the lead investigator in the MVT-5873 Phase I clinical trial.

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 (SD) response as determined by RECIST 1.1 measurements made every second cycle of therapy. One patient achieved a complete response (CR) by the first RECIST 1.1 time point at the end of the second cycle.

"Combining the results from our MVT-5873 single agent trial and our MVT-2163 immunoPET trial, whose Phase 1a results will be announced at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) annual meeting held June 10-14, 2017, gives us an opportunity to enrich patient selection for our upcoming clinical trials. We think there is a place for MVT-5873 in the treatment of CA19-9 expressing cancers including in combination with a standard of care chemotherapy for newly diagnosed treatment naïve patients. MVT-5873 is being evaluated in combination with gemcitabine and nab-paclitaxel in a second arm of this Phase I trial and we anticipate results to be available later this year. We continue to be focused on bringing more potent MVT-5873-based products into the clinic. The first of these more potent products is our radioimmunotherapy agent MVT-1075 for which we plan to initiate the Phase I trial this month," continued Mr. Hansen.

On June 5, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) (“Prima” or the “Company”) reported positive safety and efficacy data from the safety run-in stage of its clinical trial for IMP321 (LAG-3Ig) in metastatic breast cancer (MBC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 53rd annual meeting in Chicago, Illinois
AIPAC (Active Immunotherapy PAClitaxel) is Prima’s multicentre, Phase IIb, randomised, double-blind, placebo-controlled study in hormone receptor-positive MBC patients receiving IMP321 or placebo as adjunctive to first-line weekly chemotherapy, paclitaxel(Press release, Prima Biomed, JUN 5, 2017, View Source [SID1234519441]).

The safety run-in phase trialled the safety, immune-monitoring and activity of 15 patients. At both the 6mg and 30mg dose levels, IMP321 was shown to be safe and well tolerated. The higher 30mg dose demonstrated a stronger immune response, and was determined to be the recommended phase two dose (RPTD) for the ongoing randomised phase of 226 patients.
In addition, the safety run-in phase demonstrated that IMP321:

• in combination with paclitaxel shows an encouraging disease control rate (DCR) of 87%;

• leads to a sustainable (more than 6 month) increase and activation of antigen presenting cells (APCs), the primary PharmacoDynamic (PD) marker; and

• leads to a sustainable (more than 6 month) increase in CD8 T-cell and natural killer (NK) cell numbers, together with an improved pre-dose Th1 status, the secondary PD marker.
Prima’s Chief Medical Officer, Dr Frédéric Triebel, said: “This very positive data is a major milestone for our AIPAC trial. It further supports previous clinical data in metastatic breast cancer, which led to Prima designing and starting AIPAC along with Scientific Advice from the European Medicines Agency (EMA). The similar disease-free rate to that 30 patient trial, and stronger immune response from the higher 30mg dose further underpins the randomised phase for AIPAC currently underway.
The increase of APC numbers in the blood and their activation, which stimulate the body’s immune response to fight cancer cells, has not previously been seen with other immune checkpoint inhibitors as IMP321 has a broader mode of activation, not restricted to T cells. Furthermore, the increased numbers of CD8 T cells and natural killer cells, and corresponding baseline Th1 status is a very positive indicator of the potential efficacy of IMP321 as these are known to be related to anti-tumour efficacy in patients.”
The poster presentation, titled “Combination of paclitaxel and LAG-3Ig (IMP321), a novel MHC class II agonist, as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Interim results from the run-in phase of a placebo controlled randomized phase II” was delivered by lead author, Dr Francois P. Duhoux from Université Catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium on Sunday, 4th June.
The full poster presentation can be found on the Prima BioMed website at www.primabiomed.com.au. Details of the AIPC study are posted on www.clinicaltrials.gov (clinicaltrials.gov identifier NCT 02614833).

On June 5, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima" or the "Company") reported positive safety and efficacy data from the safety run-in stage of its clinical trial for IMP321 (LAG-3Ig) in metastatic breast cancer (MBC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 53rd annual meeting in Chicago, Illinois
AIPAC (Active Immunotherapy PAClitaxel) is Prima’s multicentre, Phase IIb, randomised, double-blind, placebo-controlled study in hormone receptor-positive MBC patients receiving IMP321 or placebo as adjunctive to first-line weekly chemotherapy, paclitaxel(Press release, Prima Biomed, JUN 5, 2017, View Source [SID1234519441]).

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The safety run-in phase trialled the safety, immune-monitoring and activity of 15 patients. At both the 6mg and 30mg dose levels, IMP321 was shown to be safe and well tolerated. The higher 30mg dose demonstrated a stronger immune response, and was determined to be the recommended phase two dose (RPTD) for the ongoing randomised phase of 226 patients.
In addition, the safety run-in phase demonstrated that IMP321:

• in combination with paclitaxel shows an encouraging disease control rate (DCR) of 87%;

• leads to a sustainable (more than 6 month) increase and activation of antigen presenting cells (APCs), the primary PharmacoDynamic (PD) marker; and

• leads to a sustainable (more than 6 month) increase in CD8 T-cell and natural killer (NK) cell numbers, together with an improved pre-dose Th1 status, the secondary PD marker.
Prima’s Chief Medical Officer, Dr Frédéric Triebel, said: "This very positive data is a major milestone for our AIPAC trial. It further supports previous clinical data in metastatic breast cancer, which led to Prima designing and starting AIPAC along with Scientific Advice from the European Medicines Agency (EMA). The similar disease-free rate to that 30 patient trial, and stronger immune response from the higher 30mg dose further underpins the randomised phase for AIPAC currently underway.
The increase of APC numbers in the blood and their activation, which stimulate the body’s immune response to fight cancer cells, has not previously been seen with other immune checkpoint inhibitors as IMP321 has a broader mode of activation, not restricted to T cells. Furthermore, the increased numbers of CD8 T cells and natural killer cells, and corresponding baseline Th1 status is a very positive indicator of the potential efficacy of IMP321 as these are known to be related to anti-tumour efficacy in patients."
The poster presentation, titled "Combination of paclitaxel and LAG-3Ig (IMP321), a novel MHC class II agonist, as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Interim results from the run-in phase of a placebo controlled randomized phase II" was delivered by lead author, Dr Francois P. Duhoux from Université Catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium on Sunday, 4th June.
The full poster presentation can be found on the Prima BioMed website at www.primabiomed.com.au. Details of the AIPC study are posted on www.clinicaltrials.gov (clinicaltrials.gov identifier NCT 02614833).