On March 23, 2018 Euronext Paris: FR0010331421 – IPH) reported that its partner MedImmune, AstraZeneca’s global biologics research and development arm, has amended the clinical trial protocol of the ongoing Phase I trial investigating the safety and efficacy of monalizumab, Innate’s investigational first-in-class anti-NKG2A monoclonal antibody, in combination with AstraZeneca’s approved anti-PD-L1 immune checkpoint inhibitor, durvalumab, in patients with advanced solid tumors (Press release, Innate Pharma, MAR 23, 2018, http://www.innate-pharma.com/en/news-events/press-releases/partner-medimmune-expands-colorectal-cancer-patient-cohort-ongoing-phase-i-trial-evaluating-monalizumab-combination-imfinzir-durvalumab [SID1234525390]). The trial protocol has been expanded to add new expansion cohorts aiming at testing monalizumab in combination with durvalumab and standard of care in patients with 1st- and 2nd-line, metastatic colorectal cancer (CRC).

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The dose-escalating part of the study has been completed, while the expansion cohorts in selected advanced solid tumors are ongoing.
The primary objective of the new study arms will be safety, with Overall Response Rate (ORR) and Duration of Response (DOR), amongst others, as secondary outcome measures.
Pierre Dodion, Chief Medical Officer of Innate Pharma, commented: "We are delighted that our partner MedImmune has decided to further expand the colorectal patient population to evaluate the safety and efficacy of monalizumab in combination with durvalumab and the current standard of care in 1st- and 2nd-line therapy. In addition, we look forward to the first clinical data read-outs from the Phase I study and initial expansion cohort program during 2018."
An update to study D419NC00001 including the new additional study arms has been published on clinicaltrials.gov.

On March 23, 2018 Eisai Co., Ltd. and Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the multiple receptor tyrosine kinase inhibitor LENVIMA (lenvatinib mesylate) has been approved in Japan for unresectable hepatocellular carcinoma (HCC) (Press release, Merck & Co, MAR 23, 2018, View Source [SID1234525467]). This is the first approval worldwide for LENVIMA for the indication of unresectable HCC and the first new systemic therapy to be approved in Japan for the front line treatment of HCC in approximately 10 years. Additionally, this is the first regulatory approval for LENVIMA under the global strategic collaboration agreement executed in March 2018 between Eisai and Merck for the co-development and co-commercialization of LENVIMA.

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This approval was based on a phase 3 clinical study (Study 304/REFLECT study) conducted by Eisai investigating LENVIMA as a first-line treatment in patients with unresectable HCC. In this study, LENVIMA demonstrated statistically significant non-inferiority of overall survival (OS) (13.6 months) compared to sorafenib (12.3 months) (hazard ratio [HR] 0.92, 95% confidence interval [CI]=0.79-1.06). Additionally, LENVIMA showed highly statistically significant and clinically meaningful improvements as compared to sorafenib in the secondary endpoints of progression-free survival (PFS) (HR 0.66, 95% CI=0.57-0.77, p<0.00001), time to progression (TTP) (HR 0.63, 95% CI=0.53-0.73, p<0.00001), and objective response rate (ORR) (LENVIMA 24% versus sorafenib 9%, p<0.00001). Furthermore, LENVIMA helped to delay deterioration in several quality of life (QOL) and symptom domains (pre-specified secondary endpoint), including in areas such as pain and diarrhea, compared to sorafenib (nominal p-value<0.05).

In this study, the five most common adverse events observed in the LENVIMA arm were hypertension (42%), diarrhea (39%), decreased appetite (34%), weight loss (31%) and fatigue (30%), which is consistent with the known safety profile of LENVIMA.

Liver cancer is the second leading cause of cancer-related deaths, with approximately 750,000 deaths per year estimated globally. Additionally, approximately 780,000 cases are newly diagnosed each year, about 80 percent of which occur in Asia, including Japan and China. HCC accounts as the primary reason for 85 percent to 90 percent of liver cancer cases. It is estimated that there are approximately 42,000 HCC patients in Japan, with approximately 26,000 deaths every year. To date, treatment options for unresectable HCC have been limited, and the prognosis is very poor, emphasizing that this is an area of high unmet medical need.

"With the approval of this additional indication of unresectable HCC for LENVIMA, we are proud to be able to deliver the first new front-line systemic therapy treatment option for HCC in Japan in approximately 10 years, and expect this will contribute to HCC treatment," said Dr. Takashi Owa, Eisai Oncology Business Group Chief Medicine Creation Officer. "Eisai will continue with its efforts in oncology research and development in order to deliver hopes for a potential cure for cancer to patients and their families."

"Today’s approval is an important first for LENVIMA and a significant first regulatory event under our collaboration with Eisai," said Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories. "We congratulate Eisai on the approval of this new indication and look forward to working together to bring this important treatment option to patients."

Having received approval of this indication, Eisai will receive a development milestone payment from Merck. There are no changes to Eisai’s consolidated financial results forecasts for the fiscal year ending March 31, 2018 based on the receipt of this milestone payment.

LENVIMA Product Details in Japan (underlined parts have been added)

1) Product name

LENVIMA Capsule 4 mg

2) Generic name

Lenvatinib mesylate

3) Indication

Unresectable thyroid cancer, unresectable hepatocellular carcinoma

4) Dosage and Administration

Unresectable thyroid cancer

The usual adult dose is 24 mg as lenvatinib administered orally once a day. The dose may be reduced depending on the condition of the individual patient.

Unresectable hepatocellular carcinoma

The usual adult dose is an amount of lenvatinib in accordance with body weight administered orally once a day. For adults weighing 60 kg and over, the dose should be 12 mg. For adults weighing less than 60 kg, the dose should be 8 mg. The dose may be reduced depending on the condition of the individual patient.

About LENVIMA (lenvatinib mesylate) capsules, 10 mg and 4 mg

Discovered by Eisai, LENVIMA is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

Currently, LENVIMA is approved as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a treatment for renal cell carcinoma (second-line) in over 40 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma.

Outside of Japan, Eisai has submitted applications for an indication covering hepatocellular carcinoma in the United States and Europe (July 2017), China (October 2017), Taiwan (December 2017) and other countries

On March 23, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that Keith Orford, M.D., Ph.D, the company’s Senior Vice President of Clinical Development, will present at the Needham & Company 17th Annual Healthcare Conference at 2:00 p.m. ET on Wednesday, March 28, 2018 in New York City (Press release, Calithera Biosciences, MAR 23, 2018, View Source [SID1234535243]). The presentation will be webcast live and available for replay for up to 30 days at www.calithera.com in the Investor Relations section

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On March 23, 2018 – Clovis Oncology, Inc. (NASDAQ:CLVS) reported the initiation of an early access program in Europe for rucaparib for treatment and as maintenance therapy in recurrent ovarian cancer (Press release, Clovis Oncology, MAR 23, 2018, View Source;p=RssLanding&cat=news&id=2339489 [SID1234524963]). The program will be overseen and implemented by Caligor Coghlan, which specializes in early access to medicines.

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The program, to be known as the Rucaparib Access Program (RAP), will enable participation from certain countries in Europe, where permitted by applicable rules, procedures and regulatory authorities. The RAP protocol allows for rucaparib treatment of an individual patient with third-line or greater BRCA mutant epithelial, fallopian tube, or primary peritoneal ovarian cancer who has platinum-sensitive disease and is unable to tolerate further platinum-based chemotherapy or has platinum-resistant disease and needs treatment with single agent rucaparib. The RAP protocol will also provide access to rucaparib for maintenance therapy of an individual patient with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who has received at least two prior platinum-based treatment regimens, has platinum-sensitive disease, and is in a complete or partial response to the most recent platinum-based regimen. In all cases, the patient must have a special clinical need that cannot be met by current licensed available medicines. Patients must be ineligible for Clovis’ ARIEL4 clinical trial or unable to access a participating ARIEL4 site to qualify for Clovis’ early access program.

Questions or inquiries regarding the RAP should be directed to [email protected].

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. Studies open for enrollment or under consideration include ovarian, prostate, breast, gastroesophageal, pancreatic, lung and bladder cancers. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved on an accelerated basis as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer, who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for Rubraca. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. In December 2017, the U.S. Food and Drug Administration (FDA) accepted the Company’s supplemental New Drug Application (sNDA) for Rubraca for a second-line or later maintenance treatment indication in ovarian cancer based on the ARIEL3 data. The FDA granted Priority Review status to the application with a Prescription Drug User Fee Act (PDUFA) date of April 6, 2018.

Rubraca is an unlicensed medical product outside of the U.S.

About Early Access Programs

Early Access Programs provide companies with a way to allow ethical access to their pre-license/unlicensed medicines to help patients with unmet medical needs. Access is provided in response to physician requests, in a fully compliant manner, where no alternative treatment options are available.

On March 23, 2018 Amgen (NASDAQ:AMGN) and Allergan plc. (NYSE:AGN) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the marketing authorization of ABP 980, a biosimilar to Herceptin (trastuzumab) (Press release, Amgen, MAR 23, 2018, View Source;p=RssLanding&cat=news&id=2339486 [SID1234525391]). ABP 980 has been recommended for approval for the treatment of the same three types of cancer as Herceptin is approved for in the European Union (EU), including HER2-positive metastatic breast cancer, HER2-positive early breast cancer and HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction.

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"The positive opinion issued by the CHMP for ABP 980 marks an important step for our biosimilar portfolio, as it’s our second oncology biosimilar to reach this important milestone, and further underscores our commitment to providing the oncology community access to high-quality cancer therapies," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to continuing our work with Allergan and European regulatory authorities to bring additional options to patients with cancer."

The Marketing Authorization Application for ABP 980 was supported by analytical, pharmacokinetic and clinical data, as well as pharmacology and toxicology data. The Phase 3 comparative efficacy, safety and immunogenicity study was conducted in adult female patients with HER2-positive early breast cancer.

"We are committed to providing patients with important medicines to help them fight cancer," said David Nicholson, chief research and development officer at Allergan. "The CHMP’s positive opinion for the marketing authorization of ABP 980 reinforces its potential to increase physician choice and patient access to an important biologic."
The CHMP positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the EU. If approved, a centralized marketing authorization will be granted that will be valid in the 28 countries that are members of the EU. Norway, Iceland and Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions on the basis of the EC’s decision.

Amgen and Allergan are collaborating on the development and commercialization of four oncology biosimilars. Amgen has a total of 10 biosimilars in its portfolio, two of which have been approved by the EC.
About ABP 980

ABP 980 is being developed as a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody approved in many regions for the treatment of HER2-overexpressing early breast cancer, adjuvant breast cancer, metastatic breast cancer and metastatic gastric cancer. The active ingredient of ABP 980 is a humanized monoclonal antibody that has the same amino acid sequence as trastuzumab. ABP 980 has the same pharmaceutical dosage form and same strength after reconstitution as trastuzumab. Amgen and Allergan also submitted a Biologics License Application to the U.S. Food and Drug Administration (FDA) for ABP 980 in 2017.