On July 7, 2015 CureVac, a clinical-stage biopharmaceutical company pioneering the field of mRNA-based technology, reported that a Phase I/IIa study of the company’s mRNA cancer immunotherapy (CV9103) in advanced castration-resistant prostate cancer was published in the peer-reviewed Journal for ImmunoTherapy of Cancer ((Press release, CureVac, JUL 7, 2015, View Source [SID1234518778]). CV9103 is a self-adjuvanted, sequence-optimized, chemically unmodified mRNA immunotherapy targeting four antigens: prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), and six- transmembrane epithelial antigen of the prostate 1 (STEAP1). The research article, titled "Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study," describes CureVac’s clinical study of CV9103 in 44 patients with advanced castration-resistant prostate cancer. The related data signify the first Phase IIa clinical study in which an mRNA therapy has demonstrated antigen- specific immune responses in the majority of patients. Based on the favorable data, CureVac is currently conducting a randomized, placebo-controlled Phase IIb study in 197 prostate cancer patients with the follower vaccine CV9104 targeting six antigens. Ingmar Hoerr, CEO of CureVac, commented, "We are very pleased that the results of this Phase I/IIa clinical study of our RNActive technology were published in such an esteemed peer-reviewed journal as it validates our leadership position in mRNA therapeutics and highlights the continued advancement of our clinical pipeline. Prostate cancer remains our most advanced program, with the Phase IIb clinical trial progressing as planned, but CureVac also possesses a deep and diverse mRNA-driven pipeline spanning six clinical trials with more than 300 individuals treated so far and about 15 programs targeting multiple treatment opportunities and disease indications." As described in the article, the Phase I part of the study was designed to investigate the safety and recommended dosage of CV9103, with 12 patients up to five intradermal injections of 256 (n = 3), 640 (n = 3), or 1280 μg (n = 6) mRNA. In the Phase IIa part, 32 patients were enrolled to receive the recommended dose of 1280 μg mRNA defined in Phase I. The primary endpoint of the study was safety and tolerability, and the secondary endpoint was induction of antigen specific immune responses monitored at baseline and at weeks 5, 9 and 17. Data indicated that CV9103 was well tolerated, with the majority of related adverse events being of mild to moderate intensity. The most frequent treatment-related side effects were injection site erythema and injection site reaction in 27 (61%) and 21 (48%) patients, respectively. A quantitative analysis of ELISpot, ICS, and tetramer staining assays revealed that CV9103 was able to induce both CD4 and CD8 T cell responses. Of the 33 evaluable patients treated at 1280 μg, a cellular immune response could be detected in 25 (76%). Importantly immune responses against all four antigens could be induced indicating the versatility of the platform. Arnulf Stenzl, Medical Director of the Department of Urology, University of Tübingen Medical School, and senior author of the paper, stated, "The data generated by this Phase I/IIa clinical study demonstrate that CV9103 mRNA was well tolerated and immunogenic. Furthermore a trend towards longer survival time was also observed in immune responders that was strongest in patients responding to multiple antigens CV9103. Based on these results, it is evident that this mRNA technology warrants further clinical investigation." Just recently, CureVac published promising data of its RNArt technology platform in Molecular Therapy that demonstrated for the first time that sequence-optimized, chemically unmodified mRNAs raised relevant protein levels in non-human primates, indicating that mRNA achieves meaningful biological effects in large animals with body weight close to humans.

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On July 7, 2015 Provectus Pharmaceuticals reported that varied locoregional treatments for hepatocellular carcinoma and metastatic colorectal cancer liver metastases are producing promising clinical results, according to a study presented here at the 2015 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer (ESMO-GI) (Press release, Provectus Pharmaceuticals, JUL 7, 2015, View Source [SID:1234506186]).

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"We have seen interesting data on locoregional therapies for hepatocellular carcinoma and colon cancer," stated Chris Verslype, MD, University Hospital, Leuven, Belgium, on July 4. "These therapies are gaining interest due to the fact that the liver is the predominant site of disease for most of these tumours."

Dr. Verslype commented on trials across several phases presented at the meeting.

Guy van Hazel, MD, University of Western Australia, Perth, Australia, updated and extended results, on July 4, of SIRFLOX, a phase 3 trial of first-line FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)-based chemotherapy with or without selective internal radiation therapy (SIRT) in metastatic colorectal cancer patients with liver-dominant metastases. Improvement in progression-free survival, the primary endpoint, was not achieved in patients receiving SIRT. Disease progression in the liver, however, was reduced by 31% in patients receiving SIRT (SIR-Spheres; delivered as yttrium-90 microspheres via a hepatic artery injection).

Dr. van Hazel’s new SIRFLOX data pertained to 318 patients (159 FOLFOX plus bevacizumab; 159 FOLFOX plus bevacizumab plus SIRT) who had metastases only in the liver. Among them, progression-free survival with SIRT was extended by 8.7 months (FOLFOX plus bevacizumab, 12.4 months; FOLFOX plus bevacizumab plus SIRT, 21.1 months; hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.48-0.86; P = .003). Among patients who had liver and extrahepatic metastases, however, the improvement in progression-free survival with SIRT was not significant (16.7 vs 12.6 months; P = .147). Dr. van Hazel noted that cumulative incidence of liver progression was superior for SIRT in patients with or without bevacizumab (P = .018 and .028, respectively).

"We saw that first-line radioembolisation in combination with bevacizumab and chemotherapy is able to retard progression in the liver, and it does seem to be safe," commented Dr. Verslype. "We feel, at our institution in Leuven, that we should restrict this to patients with very limited extrahepatic disease, where we can probably make a difference in the long run for our patients."

The phase 2 EORTC (European Organisation for Research and Treatment of Cancer) 40004/CLOCC trial, the first study prospectively investigating the efficacy of radiofrequency ablation added to standard systemic treatments in patients with nonresectable colorectal liver metastases, included 152 patients randomised to 6 months of systemic treatment with or without radiofrequency ablation. In ~75% of the patients, the systemic treatment was FOLFOX (with bevacizumab in ~17%). Prior reports showed the primary objective of overall survival of >38% at 30 months to have been met with 61.7% overall survival in the group receiving systemic treatment plus radiofrequency ablation and with 57.6% overall survival among those receiving systemic treatment only (NS), said Theo Ruers, MD, The Netherlands Cancer Institute, Antoni Van Leeuwenhoek Ziekenhuis, Amsterdam, The Netherlands, on July 3. Median progression-free survival, however, at a median follow-up of 4.4 years, was significantly longer for the radiofrequency group (16.8 vs 9.9 months; HR, 0.63; P = .025).

Progression-free survival at a median follow-up of 9.7 years was 2.0% for those receiving systemic therapy and 22.3% for systemic therapy plus radiofrequency ablation (HR, 0.57: 95% CI, 12.7-33.7; P = .005). Eight-year overall survival was 8.8% for systemic therapy alone and 35.9% for radiofrequency ablation (HR, 0.58, 95%; 95% CI, 0.38-0.88; P = .01). Progressive disease was the main cause of death (56.7% systemic plus radiofrequency ablation, 81.4% systemic only).

The findings, despite the small sample size, "encourage the use of ablative techniques as a treatment modality in patients with nonresectable colorectal liver metastases," said Dr. Ruer.

A third study, a phase 1 study of locoregional chemoablation with PV-10 (10% rose bengal solution), included patients with liver tumours (nonresectable hepatocellular carcinoma or liver metastases) of ≥1 cm.

The study demonstrated safety and activity, said Paul Goldfarb, MD, Sharp Clinical Oncology Research, San Diego, California, on July 2. PV-10 has shown high complete response rates and durable local control in phase 2 testing in metastatic melanoma and is currently in phase 3 testing.

This first presentation of 6 patients with evaluable liver data revealed only injection-site and photosensitivity reactions, with stable disease in all tumours and some partial responses. An expansion cohort includes 24 patients.

PV-10 is injected directly into lesions and has been shown to have effects on noninjected and distant lesions.

"We may expect some immunological effects with this kind of treatment, so locoregional treatment doesn’t necessarily mean that the effect of the therapy remains limited to the tumour itself in the liver. There may be effects on distant tumour sites," Dr. Verslype concluded.

On July 7, 2015 NanoString Technologies reported the publication of a study online in Clinical Cancer Research that reinforces the ability of the company’s Prosigna Breast Cancer Assay to inform physician treatment decisions by predicting which patients are most likely to benefit from chemotherapy (Press release, NanoString Technologies, JUL 7, 2015, View Source [SID:1234506184]). The study, entitled "Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay," was conducted in collaboration with Spanish researchers from Vall d’Hebron Institute of Oncology (VHIO), University of Barcelona, and University Hospital ‘Virgen de la Victoria’ of Malaga. The publication can be found online at View Source

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"These results highlight the value of considering tumor biology in the diagnostic evaluation of early stage breast cancer," said Dr. Aleix Prat, Head Medical Oncology Department at Hospital Clínic, University of Barcelona and Principal Investigator. "The results also support the findings of prior studies, which have shown that ROR score and intrinsic subtype are strong predictors of response to chemotherapy."

The study authors evaluated the correlation between numerical risk score provided by Prosigna, referred to as the ROR or Prosigna score, and response to a modern neoadjuvant chemotherapy (NAC) regimen consisting of anthracyclines and taxanes. The study demonstrated that ROR score and intrinsic subtype as determined by Prosigna are strong predictors of response to NAC, confirming expectations that high-risk tumors are significantly more responsive to systemic chemotherapy than low-risk tumors. The authors reported that ROR score significantly predicted pathologic complete response to NAC in hormone receptor-positive patients with node-negative or node-positive (1-3 positive nodes) disease (p = 0.027). Further analysis revealed that for every 20 point increase in the ROR score, a patient was 59.1% more likely to respond to NAC. Finally, the authors concluded that intrinsic subtypes, as determined by Prosigna, are predictive of chemotherapy sensitivity, as referenced in the recently updated St. Gallen International Breast Cancer Guidelines.

"This new evidence confirms Prosigna’s ability to predict response to chemotherapy," said Brad Gray, President and Chief Executive Officer of NanoString. "These results are complementary to the large body of data showing that Prosigna identifies women who are at such low risk that they may be spared overtreatment with chemotherapy."

Although the reported study results were based on the analysis of core needle biopsies, Prosigna is currently indicated for use with excisional biopsies only. Additionally, in the United States, the Prosigna patient report does not include information related to intrinsic subtype.

About the Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Dx Analysis System

The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor tissue previously diagnosed as invasive breast carcinoma.

The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Breast Cancer Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

In the United States, the Prosigna Assay is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand, Turkey, South Africa and Hong Kong.

In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:

(1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes.

For more information, please visit www.prosigna.com.

On July 7, 2015 Clovis Oncology reported that it has commenced an underwritten public offering of shares of its common stock to raise aggregate proceeds of approximately $275 million (Press release, Clovis Oncology, JUL 7, 2015, View Source;p=RssLanding&cat=news&id=2065404 [SID:1234506183]). All shares of the common stock to be sold in the offering will be offered by Clovis Oncology.

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Clovis Oncology intends to use the net proceeds of the offering for general corporate purposes, including commercial planning and sales and marketing expenses associated with the potential launches of rociletinib and rucaparib, if approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the United States and the European Union, respectively, funding of its development programs, general and administrative expenses, acquisition or licensing of additional product candidates or businesses and working capital.

J. P. Morgan Securities LLC is acting as lead book-running manager and representative of the underwriters for the offering. Credit Suisse Securities (USA) LLC is also acting as a joint book-runner, and Stifel and Mizuho Securities are acting as co-managers for the offering.

In addition, Clovis Oncology intends to grant the underwriters a 30-day option to purchase up to an additional 15 percent of the number of shares sold on the same terms and conditions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

This offering is being made only by means of a prospectus supplement and related prospectus. Copies of the prospectus supplement and related prospectus relating to this offering may be obtained from J. P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by calling toll-free (866) 803-9204.

The shares are being offered pursuant to an effective shelf registration statement. This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor will there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.