On September 27, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will today present results from a Phase Ib study evaluating the efficacy and safety of Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as a treatment for people with unresectable hepatocellular carcinoma (HCC), the most common form of liver cancer, who have not received prior systemic therapy (Press release, Hoffmann-La Roche, SEP 27, 2019, View Source [SID1234539848]).1

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Data from the non-randomised Tecentriq and Avastin cohort (Arm A) showed clinically meaningful and durable responses after a median follow-up of 12.4 months, with a confirmed objective response rate (ORR) of 36% (95% CI 26–46) by central review per RECIST v1.1. The data also showed that 12% of people had a complete response to treatment and a median duration of response (DOR) was not yet reached. Median progression-free survival (PFS), by central review per RECIST v1.1, a secondary efficacy endpoint in the study, was 7.3 months (95% CI 5.4–9.9).2 Safety for the combination of Tecentriq and Avastin appeared to be consistent with the known safety profile of the individual medicines. No new safety signals were identified.

For the randomised portion of the study (Arm F), evaluating the combination approach with Tecentriq and Avastin versus Tecentriq alone, the primary efficacy endpoint of PFS as assessed by central review per RECIST v1.1 was met, with the combination reducing the risk of disease worsening or death by 45% compared with Tecentriq monotherapy. After a median follow-up of 6.6 months, the results demonstrate the superiority of the combination of Tecentriq and Avastin over Tecentriq monotherapy (hazard ratio =0.55, 80% CI 0.40–0.74, p=0.0108). Median PFS in the Tecentriq and Avastin arm was 5.6 months (95% CI 3.6–7.4) compared with 3.4 months (95% CI 1.9–5.2) in the Tecentriq monotherapy arm.2 Additional secondary endpoints of Arm F are being evaluated and at this time the data remain immature. Safety for both cohorts in Arm F appeared to be consistent with the known safety profile of the individual medicines. No new safety signals were identified.

"We are encouraged by these latest results, which show promising progression-free survival and confirmed objective response rates in people with unresectable hepatocellular carcinoma, a disease for which the unmet medical need is particularly great," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "These data strengthen our belief in the combination of Tecentriq and Avastin in this common form of liver cancer and we look forward to the results from our Phase III study, IMbrave150."

The data (Abstract #LBA39) will be presented at 14:15 in the Proffered Paper session (14:00–15:30) in the Madrid Auditorium (Hall 2), at ESMO (Free ESMO Whitepaper) on Friday 27 September.

In July 2018, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) for Tecentriq in combination with Avastin as an initial (first-line) treatment for advanced or metastatic HCC based on data from this Phase Ib study.

Earlier this year, enrolment was completed for IMbrave150 (NCT03434379), an open-label, multicentre, randomised Phase III study investigating the combination of Tecentriq and Avastin versus sorafenib in people with unresectable HCC who have not received prior systemic therapy. The study is expected to read out later this year.

Roche has an extensive clinical trial development programme for Tecentriq, with studies ongoing or planned, including multiple Phase III studies, across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the GO30140 study (NCT02715531)
GO30140 is an open-label, multicentre Phase Ib study evaluating the safety and efficacy of Tecentriq (anti-PD-L1 antibody) administered in combination with Avastin and/or other treatments in people with solid tumours, including HCC. In Arms A and F of the study, people with unresectable HCC who had not received prior systemic therapy were eligible for enrolment. All patients in Arm A received Tecentriq and Avastin. Patients in Arm F were randomised 1:1 to receive Tecentriq and Avastin or Tecentriq monotherapy. Patients on the combination received Tecentriq (1200 mg) and Avastin (15 mg/kg) intravenously every 3 weeks, while those in the monotherapy cohort received Tecentriq (1200 mg) intravenously every 3 weeks. In all cohorts, treatment continued until unacceptable toxicity or loss of clinical benefit. Primary endpoints were ORR (Arm A) and PFS (Arm F) by central review per RECIST v1.1, and safety (both arms).

About hepatocellular carcinoma (HCC)
HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.1 The disease affects over 750,000 people every year,1,3 with the majority of cases in Asia and almost half of all cases in China.3,4 HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage.1 The prognosis for unresectable HCC remains limited, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.5

About IMbrave150 (NCT03434379)
IMbrave150 is a global Phase III, multicentre, open-label study of 480 people with unresectable HCC who have not received prior systemic therapy. People are randomised 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq is administered intravenously, 1200 mg on day 1 of each 21-day cycle, and Avastin is administered intravenously, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib is administered by mouth, 400 mg twice per day, on days 1–21 of each 21-day cycle. People receive the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints are overall survival (OS) and PFS by central review per RECIST v1.1. Secondary endpoints include ORR, PFS, time to progression (TTP) and DOR all assessed by the investigator per RECIST v1.1 and HCC mRECIST, as well as ORR, TTP and DOR by central review per RECIST v1.1, along with time to deterioration (TTD) in patient-reported global health status/quality of life (GHS/QoL).

About the Tecentriq and Avastin combination
There is a strong scientific rationale to support the use of Tecentriq and Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasize).

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

On September 27, 2019 Citius Pharmaceuticals, Inc. ("Citius") ("Company") (NASDAQ: CTXR), a specialty pharmaceutical company focused on adjunctive cancer care and critical care drug products, reported the closing of the previously announced underwritten at-the-market offering of 7,821,230 shares of its common stock (Common Stock) (or Common Stock equivalent) and common warrants to purchase up to an aggregate of 7,821,230 shares of Common Stock (the Offering) (Press release, Citius Pharmaceuticals, SEP 27, 2019, View Source [SID1234539864]). Each share of Common Stock (or Common Stock equivalent) was sold together with a common warrant to purchase one share of Common Stock at a combined effective price of $0.8951 per share and accompanying common warrant. The Company has granted the underwriter a 30-day option to purchase up to an additional 1,173,184 shares of Common Stock and/or common warrants to purchase up to 1,173,184 shares of Common Stock.

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H.C. Wainwright & Co. acted as the sole book-running manager for the Offering.

The gross proceeds of the Offering were approximately $7.0 million and the net proceeds from the Offering were approximately $6.1 million, after deducting underwriting discounts and commissions and other offering expenses. Citius intends to use the net proceeds from the Offering for general corporate purposes, including its Phase 3 clinical Mino-Lok trial for the treatment of catheter related bloodstream infections, the investigational new drug (IND) regulatory pathway for Mino-Wrap and its Phase 2b clinical trial of Halo-Lido cream for the treatment of hemorrhoids, and working capital and capital expenditures.

The common warrants issued in the Offering are exercisable immediately at an exercise price of $0.77 per share and will expire five years from the date of issuance.

A registration statement on Form S-1 (File No. 333-233759) relating to the securities was declared effective by the U.S. Securities and Exchange Commission (SEC) on September 24, 2019. The Offering was made only by means of a prospectus forming part of the effective registration statement. A final prospectus relating to and describing the terms of the Offering has been filed with the SEC. Electronic copies of the final prospectus relating to the Offering may be obtained for free by visiting the SEC’s website at www.sec.gov or from H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, New York 10022, by email at [email protected] or by telephone at 646-975-6996.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On September 27, 2019 Incyte (Nasdaq:INCY) reported updated results, including the final result for the primary endpoint, from its Phase 2 FIGHT-202 trial evaluating pemigatinib, a selective fibroblast growth factor receptor (FGFR) inhibitor, as a treatment for patients with previously treated, locally advanced or metastatic cholangiocarcinoma (Press release, Incyte, SEP 27, 2019, View Source [SID1234539849]). In patients harboring FGFR2 fusions or rearrangements (Cohort A), pemigatinib monotherapy resulted in an overall response rate (ORR) of 36 percent (primary endpoint), and median progression free survival (PFS) of 6.9 months (secondary endpoint) with a median follow-up of 15 months. Pemigatinib was generally well tolerated.

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These results are being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona, Spain during a late-breaking oral session today, September 27, from 3:00 p.m. CEST to 3:15 p.m. CEST (9:00 a.m. EDT to 9:15 a.m. EDT) in Madrid Auditorium (Hall 2); Abstract #LBA40.

"We are excited to share updated data for pemigatinib, which may provide a promising and targeted treatment approach for patients with cholangiocarcinoma harboring FGFR2 fusions or rearrangements," said Peter Langmuir, M.D., Group Vice President, Targeted Therapeutics, Incyte. "Patients with advanced cholangiocarcinoma face a poor prognosis, and currently there is no standard of care beyond first-line chemotherapy. We are committed to advancing pemigatinib, a potent and selective therapy targeting a key driver of this disease, and plan to submit the New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) shortly."

Cholangiocarcinoma is a rare cancer that forms in the bile duct. It is classified based on its origin: intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. Patients with cholangiocarcinoma are often diagnosed at a late or advanced stage when the prognosis is poor.1,2 The incidence of cholangiocarcinoma varies regionally and ranges between 0.3 – 3.4 per 100,000 in North America and Europe.1 FGFR2 fusions or rearrangements occur almost exclusively in iCCA, where they are observed in 10-16 percent of patients.3-5

Key Findings from FIGHT-202

Updated data presented today at ESMO (Free ESMO Whitepaper) show that in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements (Cohort A, n=107), pemigatinib monotherapy resulted in a confirmed overall response rate (ORR) of 36 percent based on an independent central radiographic review, including 3 patients with a complete response (CR) and 35 patients with a partial response (PR). In these patients, the disease control rate (DCR) was 82 percent, median duration of response (DOR) was 7.5 months, and median progression free survival (PFS) was 6.9 months. Preliminary overall survival (OS) data were encouraging (median: 21.1 months) and follow-up will continue as these data are not yet mature.

FIGHT-202 Overall Response Rates (ORR), Durability of Response (DOR), Disease Control Rates
(DCR) and Progression-Free Survival (PFS) by Patient Cohort

Note: One patient did not have confirmed FGF/FGFR status by central laboratory and was included in the safety analysis but was not assigned to any cohort for efficacy.

The safety analysis, including 146 patients, showed that pemigatinib was generally well tolerated. Grade 1 or 2 hyperphosphatemia, the most common treatment-emergent adverse event (TEAE; 60 percent), was managed with a low phosphate diet, phosphate binders and diuretics, or dose reduction or interruption. The most common Grade ≥3 TEAE was hypophosphatemia (12 percent); none of the cases was considered clinically significant or serious and none led to dose reduction or discontinuation. Serous retinal detachment was observed in 4 percent of patients (Grade ≥3, 1 percent) with none of the cases resulting in clinical sequelae.

"Patients with cholangiocarcinoma face a significant challenge as they cope with a life-threatening condition that is often diagnosed once it has progressed into late stages," said Arndt Vogel, M.D., Senior Consultant and Professor at Hannover Medical School. "As a physician, I am encouraged to see the data from the FIGHT-202 study, which demonstrate the potential that pemigatinib has to become an important and much needed targeted treatment option for this patient population."

About FIGHT-202

The FIGHT-202 Phase 2, open-label, multicenter study (NCT02924376) is evaluating the safety and efficacy of pemigatinib – a selective fibroblast growth factor receptor (FGFR) inhibitor – in adult (age ≥ 18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg pemigatinib orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity.

The primary endpoint of FIGHT-202 is overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR in Cohorts B, A plus B, and C; progression free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR) and safety in all cohorts.

For more information about FIGHT-202, visit View Source

About FIGHT

The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program includes ongoing Phase 2 and 3 studies investigating safety and efficacy of pemigatinib therapy across several FGFR-driven malignancies. Phase 2 monotherapy studies include FIGHT-202, as well as FIGHT-201 investigating pemigatinib in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 mutations or fusions/rearrangements; FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 fusions/rearrangements; FIGHT-207 in patients with previously treated, locally-advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or fusions/rearrangements, irrespective of tumor type. FIGHT-205 is a Phase 2 study investigating pemigatinib plus pembrolizumab combination therapy and pemigatinib monotherapy in patients with previously untreated, metastatic or unresectable bladder cancer harboring FGFR3 mutations or fusions/rearrangements who are not eligible to receive cisplatin. FIGHT-302 is a recently initiated Phase 3 study investigating pemigatinib as a first-line treatment for patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

About FGFR and Pemigatinib

Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating fusions, rearrangements, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers.

Pemigatinib is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations. The U.S. Food and Drug Administration (FDA) has granted pemigatinib Breakthrough Therapy designation for the treatment of previously treated, advanced/metastatic or unresectable FGFR2 translocated cholangiocarcinoma. The FDA’s Breakthrough Therapy designation is designed to expedite the development and review of drugs for serious conditions that have shown encouraging early clinical results and may demonstrate substantial improvements over available medicines.

Conference Call Information

Incyte will host an investor conference call and webcast at 11:00 a.m. EDT (5:00 p.m. CEST) today, September 27, 2019—the call and webcast can be accessed via the Events and Presentations tab of the Investor section of www.incyte.com and it will be available for replay for 30 days.

To access the conference call, please dial 877-407-3042 for domestic callers or +1 201-389-0864 for international callers. When prompted, provide the conference identification number, 13694537.

On September 27, 2019 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported that management will present a company update at the following conferences (Press release, PTC Therapeutics, SEP 27, 2019, View Source [SID1234539865]):

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Cantor Global Healthcare Conference
Friday, October 4th at 10:40 a.m. ET

Chardan Genetic Medicines Conference
Monday, October 7th at 9:00 a.m. ET

The presentations will be webcast live on the Events and Presentations page under the investor relations section of PTC Therapeutics’ website at www.ptcbio.com and will be archived for 2 weeks following the presentation. It is recommended that users connect to PTC’s website several minutes prior to the start of the webcast to ensure a timely connection. PTC’s current Investor Presentation is available at the same website location.

On September 27, 2019 Northern Biologics Inc., a company focused on developing first-in-class oncology products, reported the presentation of updated Phase 1a trial results of its lead antibody, MSC-1, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Barcelona, Spain (Press release, Northern Biologics, SEP 27, 2019, View Source [SID1234539850]).

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MSC-1 is a humanized antibody against a soluble cytokine called LIF (see "About LIF" below). LIF plays a multi-faceted role in cancer, and antagonism of this molecule opens up two therapeutic avenues: reversal of tumor immunosuppression and modulation of cancer initiating cells (CICs) to promote tumor cell differentiation and sensitivity to chemotherapy.

The open-label, Phase 1a, dose escalation trial in the U.S., Europe and Canada is testing MSC-1 as monotherapy to determine safety and tolerability in patients with relapsed or refractory advanced solid tumors. The study completed enrollment in early March, with 41 patients enrolled in nine months, in dose cohorts ranging from 75 mg to 1,500 mg Q3W. The treatment was well-tolerated with no dose-limiting toxicities or tolerability issues observed at any dose. In addition, MSC-1 demonstrated a favorable PK profile, typical of an antibody. Durable saturation of peripheral LIF in a pharmacodynamic assay in patients supported the selection of the recommended Phase 2 dose for further development.

Prolonged stable disease (>16 weeks) was observed in nine patients, with five of these patients demonstrating progression-free survival with MSC-1 treatment longer than their most recent prior cancer therapy regimen. Finally, exploratory biomarker analysis of paired pre- and on-treatment tumor biopsies demonstrated a shift in macrophage populations in the tumor microenvironment to a more immunostimulatory phenotype, inhibition of STAT3 phosphorylation in the majority of patients, as well as increased CD8 T-cell infiltration in a subset of patients, supporting the proposed mechanism of action of MSC-1.

"The excellent safety profile of MSC-1 and the data from the Phase 1a study support the continued clinical development of MSC-1, and testing in combination with checkpoint inhibitors and chemotherapy," said Erkut Borazanci, M.D., M.S., Clinical Investigator at HonorHealth Research Institute. "We are excited to describe the effects of this first-in-class anti-LIF antibody on key biomarkers in the tumor microenvironment which are consistent with the promotion of anti-tumor inflammation. We believe this molecule has the potential to bring benefit to individuals with cancer."

"The encouraging clinical evidence of the effect of MSC-1 on the tumor microenvironment in heavily pre-treated patients, coupled with exciting preclinical data including recent publications in Nature, increase our conviction that targeting LIF can bring therapeutic benefit to cancer patients," said Philip Vickers, Ph.D., CEO of Northern Biologics.

Poster Display Session 3 (ID 212). Session Date and Time: Monday, September 30th, 2019 12:00 PM – 1:00 PM Session Location: Poster Area (Hall 4), Fira Gran Via, Poster 1196P, Abstract 1950

About LIF

LIF, or leukemia inhibitory factor, is an exciting emerging target in the immuno-oncology space. Northern Co-Founder Joan Seoane first elucidated a role for the cytokine in cancer in a seminal 2009 publication in Cancer Cell. Since that time, several independent labs have demonstrated the role of LIF in many cancers including 3 recent publications in Nature (Shi et al. Nature. 2019, Pascual-Garcia et al. Nat Commun. 2019 and Wang et al. Nat Commun. 2019). LIF is hypothesized to contribute to tumor growth and progression by acting on multiple aspects of cancer biology, including immunosuppression within the tumor microenvironment (TME), and regulation of cancer initiating cells (CICs), which are thought to underpin tumor growth, metastasis and resistance to therapy.