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).

On June 5, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the phase III ALEX study showed Alecensa (alectinib) significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by more than half (53%) compared to crizotinib when given as initial (first-line) treatment for people with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) (hazard ratio (HR)=0.47, 95% CI: 0.34-0.65, p<0.0001) (Press release, Hoffmann-La Roche, JUN 5, 2017, View Source [SID1234519438]).1 Median PFS reported by the investigators, the primary endpoint of the study, was not yet reached in people who received Alecensa (95% CI: 17.7-not reached) versus 11.1 months (95% CI: 9.1-13.1 months) in those who received crizotinib.1 Median PFS assessed by an independent review committee (IRC), a secondary endpoint, was 25.7 months (95% CI: 19.9-not reached) for people who received Alecensa versus 10.4 months (95% CI: 7.7-14.6 months) for people who received crizotinib (HR=0.50, 95% CI 0.36–0.70; p<0.0001).1 The safety profile of Alecensa was consistent with that observed in previous studies.1

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"Alecensa reduced the risk of disease progression by more than half and reduced the risk of cancer spreading to or growing in the brain, which can have devastating effects for patients," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "These results significantly improve upon the standard of care for this disease, extending the average time that people lived without their disease worsening from less than a year to more than two years. We are submitting these data to regulatory authorities around the world."

The global, randomised phase III ALEX study also demonstrated that Alecensa reduced the risk of disease progression in the central nervous system (CNS) by 84% (HR=0.16, 95% CI: 0.10-0.28; p<0.0001).1 The 12-month cumulative rate of CNS progression for people with or without existing CNS metastases at baseline was 9.4% (95% CI: 5.4-14.7%) for people treated with Alecensa and 41.4% (95% CI: 33.2-49.4%) for people treated with crizotinib.1

The official ALEX data presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting will be on Tuesday 6 June 2017, at 12:09 – 12:21 CDT (Abstract #9008). The data will be simultaneously published in the New England Journal of Medicine, and will be featured in the official ASCO (Free ASCO Whitepaper) press programme on Monday 5 June 2017 at 08:00 CDT.

Data from the ALEX study will be submitted to global health authorities, including the US Food and Drug Administration (FDA), which in September 2016 granted Alecensa Breakthrough Therapy Designation (BTD) for the treatment of people with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor.
Alecensa is approved as a monotherapy for people with ALK-positive NSCLC who have progressed on or are intolerant to crizotinib in Europe, the US and ten other countries globally. Alecensa is also approved in Japan for people whose tumours were advanced, recurrent or could not be removed completely through surgery (unresectable). In the US, Alecensa was granted accelerated approval by the FDA in December 2015 for the treatment of people with ALK-positive NSCLC who have progressed on or are intolerant to crizotinib.2 The ALEX study is part of the company’s commitment in the US to convert the current accelerated approval of Alecensa in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.

In the European Union, Alecensa was granted conditional marketing authorisation in February 2017 as monotherapy for people with ALK-positive advanced NSCLC previously treated with crizotinib.3 Under the provisions of the conditional EU approval, Roche is submitting the ALEX study as the specific obligation to obtain full approval of Alecensa as an initial treatment for ALK-positive advanced NSCLC.

About the ALEX study4
ALEX (NCT02075840/B028984) is a randomised, multicentre, open-label phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve people with ALK-positive NSCLC whose tumours were characterised as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomised (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study is PFS as assessed by the investigator and secondary endpoints include: IRC-assessed PFS, time to CNS progression, objective response rate (as defined by RECIST criteria), duration of response, overall survival, health-related quality of life and safety. The multicentre study was conducted in 303 people across 161 sites in 31 countries.4 Results include1:
Alecensa reduced the risk of disease worsening or death (PFS) by 53% compared to crizotinib (HR=0.47, 95% CI: 0.34-0.65, p<0.0001).

Investigator-reported median PFS (the primary endpoint) was not yet reached in the Alecensa arm (95% CI: 17.7 -not reached) versus 11.1 months (95% CI: 9.1-13.1 months) in the crizotinib arm.

IRC-reported median PFS (a secondary endpoint) was 25.7 months (95% CI: 19.9-not reached) in the Alecensa arm versus 10.4 months (95% CI: 7.7-14.6 months) in the crizotinib arm (HR=0.50, 95% CI: 0.36-0.70; p<0.0001).

Alecensa reduced the risk of progression in the CNS by 84% (HR=0.16, 95% CI: 0.10-0.28; p<0.0001).

The 12-month cumulative rate of CNS progression for people with or without existing CNS metastases at baseline was 9.4% (95% CI: 5.4-14.7%) for people treated with Alecensa and 41.4% (95% CI: 33.2-49.4%) for people treated with crizotinib.

Overall survival (OS) data are currently considered immature with only about a quarter of events being reported.
Grade 3-5 adverse events (AEs) were less frequent in the Alecensa arm (41%) compared to the crizotinib arm (50%). In the Alecensa arm, the most common Grade 3-5 AEs (≥5%) were increased liver enzymes (alanine transferase and aspartate transferase; 5%) and decreased red blood cells (anaemia; 5%). AEs leading to discontinuation (11% vs. 13%), dose reduction (16% vs. 21%) and dose interruption (19% vs. 25%) were all lower in the Alecensa arm compared to the crizotinib arm.

About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is an oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history.5 It is almost always found in people with a specific type of NSCLC called adenocarcinoma.5 Alecensa is currently approved in the United States, Europe, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, Australia, Singapore and Taiwan for the treatment of advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib and in Japan for people with ALK-positive NSCLC.

The global phase III ALEX study of Alecensa includes a companion test developed by Ventana. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

On June 5, 2017 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported positive clinical results from multiple studies with TRC105 and TRC102 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting in Chicago, IL (Press release, Tracon Pharmaceuticals, JUN 5, 2017, View Source [SID1234519432]).

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Observed Correlation of Biomarker Status with Activity of TRC105 with Votrient (pazopanib) in Advanced Soft Tissue Sarcoma

In this Phase 1b trial, patients who had greater than a 10% reduction in tumor volume following treatment with TRC105 and Votrient were significantly more likely to have lower baseline levels of soluble intracellular adhesion molecule-1 (ICAM-1) (p=0.018) and thrombospondin-2 (p=0.041). These biomarkers will be assessed separately as part of the completed 63 patient Phase 2 trial of TRC105 and Votrient in soft tissue sarcoma and in the ongoing randomized Phase 3 TAPPAS trial of TRC105 and Votrient in patients with angiosarcoma.

Observed Correlation of Biomarker Status with Activity of TRC105 with Inlyta (axitinib) in Advanced Renal Cell Carcinoma

In this Phase 1b trial, patients with a partial response by RECIST 1.1 following treatment with TRC105 and Inlyta were more likely to have lower levels of soluble osteopontin (p=0.026) and higher levels of soluble transforming growth factor-β receptor III (p=0.0028). These biomarkers will also be assessed as part of the ongoing randomized Phase 2 TRAXAR study of TRC105 and Inlyta in patients with renal cell carcinoma.

Data from a Phase 1/2 Trial of TRC102 with Temodar (temozolomide) in Patients with Solid Tumors

The National Cancer Institute (NCI) reported data from a trial of TRC102 in combination with Temodar in patients with refractory solid tumors. Based on partial responses in patients with KRAS-positive colorectal cancer, ovarian cancer and non-small cell lung cancer, the NCI decided to enroll expansion cohorts in each of these tumor types at the recommended Phase 2 oral dose of TRC102 of 150 mg/m2. The authors concluded that the combination of Temodar and TRC102 is active, and DNA damage response markers (Rad51, ϒ-H2AX and/or pNbs1) were induced in 4 of 5 paired colon biopsies, indicating DNA damage following treatment.

All posters are available on TRACON’s website at: www.traconpharma.com/publications.php

About Carotuximab (TRC105)

TRC105 is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in one Phase 3 and multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute for the treatment of solid tumors in combination with VEGF inhibitors. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the U.S. and EU. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 1/2 trial for patients with wet AMD. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

About TRC102

TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute or Case Comprehensive Cancer Center. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.