On June 26, 2018 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK), a clinical-stage oncology company focused on biomarker-defined cancers, reported top-line results from the CARRIE study, a randomized Phase 2 trial evaluating the addition of MM-141 (istiratumab) to standard-of-care treatment in patients with previously untreated metastatic pancreatic cancer and high serum levels of free Insulin-like Growth Factor-1 (IGF-1) (Press release, Merrimack, JUN 26, 2018, View Source [SID1234527475]). The study did not meet its primary or secondary efficacy endpoints in patients who received MM-141 in combination with nab-paclitaxel and gemcitabine, compared to nab-paclitaxel and gemcitabine alone. These results were consistent in all subgroups analyzed. Based on these results, Merrimack will not devote additional resources to the development of MM-141.

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Merrimack plans to present the complete data from this Phase 2 study at an upcoming medical oncology meeting.

"Pancreatic cancer is the third leading cause of cancer-related death in the Unites States and a very difficult cancer to treat," said Sergio Santillana, M.D., MSc., Chief Medical Officer of Merrimack. "Although we were unsuccessful in our effort to improve the standard of care for these patients, we want to express our gratitude to our investigators and our team, and, of course, to the patients and their families for their support and participation in the CARRIE study."

"While these results are disappointing, looking forward our focus remains on the continued development of our deep, wholly-owned pipeline, including two clinical programs, MM-121 and MM-310, with data readouts expected in 2018," said Richard Peters, M.D., Ph.D., President and CEO of Merrimack.

MM-121 (seribantumab), a monoclonal antibody targeting the HER3 (ErbB3) receptor, is being tested in combination with standard-of-care treatment in two randomized Phase 2 studies: SHERLOC, in patients with non-small cell lung cancer, and SHERBOC in patients with metastatic breast cancer. Both studies are enrolling patients with high tumor expression of heregulin, the signal for the HER3 receptor. Top-line results from the SHERLOC study are expected in 2H 2018.

MM-310, an antibody-directed nanotherapeutic targeting the EphA2 receptor, is currently being tested in a Phase 1 study in solid tumors, with safety data and the maximum tolerated dose expected in 2H 2018.

On June 26, 2018 Puma Biotechnology, Inc. (Nasdaq: PBYI) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive trend vote recommending the approval of the Marketing Authorisation Application (MAA) for neratinib for the extended adjuvant treatment of early stage HER2-positive hormone receptor positive breast cancer (Press release, Puma Biotechnology, JUN 26, 2018, View Source [SID1234527476]). Today’s decision follows a reexamination of the negative opinion announced by the CHMP at its formal meeting with the Company to discuss the MAA on February 23, 2018. The CHMP communicated its intention to hold a final vote at its next meeting.

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About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

On June 26, 2018 Oncology Venture US Inc., Oncology Venture AB (OV:ST) ("OV") and Medical Prognosis Institute A/S (MPI:ST) reported dosing of the first patient in a Phase 2, open-label clinical trial to investigate the anti-tumor effect and tolerability of 2X-121 in patients with metastatic breast cancer selected by a novel drug response predictor (DRP) mRNA-driven multiple biomarker, the 2X-121 DRP (Press release, 2X Oncology, JUN 26, 2018, View Source [SID1234527477]). The drug is being developed by Oncology Venture US Inc. (formerly 2X Oncology Inc.).

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"This targeted Phase 2 study will enable us to rapidly evaluate the efficacy of our Tankyrase and PARP inhibitor in heavily pre-treated metastatic breast cancer patients, using the 2X-121 DRP to prospectively select likely responders to this differentiated therapy," said George Elston, CEO of Oncology Venture US Inc.

2X-121 is an orally-available small molecule PARP and tankyrase inhibitor. This clinical trial is designed to enroll 30 metastatic breast cancer patients regardless of hormone receptor, HER2 status and BRCA1 or 2 status, who have relapsed on two or more different prior therapies and who are identified by the 2X-121 DRP as highly likely to respond to treatment with 2X-121.

The 2X-121 DRP is a novel, tumor-agnostic (i.e. independent of tumor site) molecular biomarker based on expression of 414 genes predictive of response to 2X-121. In a study presented at ASCO (Free ASCO Whitepaper), the 2X-121 DRP correctly identified responders and non-responders to treatment irrespective of BRCA mutation status. Although a patient’s BRCA status is used to identify potential responders for treatment with approved PARP inhibitors, other likely responders are excluded. The 2X-121 DRP biomarker is expected to identify those patients who are likely responders while excluding the likely non-responders.

In this clinical trial, patients will receive oral treatment with 600 mg of 2X-121, as a single agent, in a 21-day cycle. The primary endpoint of this study is clinical benefit rate, defined as complete response, partial response, or stable disease at greater than 24 weeks post-treatment using the RECIST criteria. Secondary endpoints include progression free survival, duration of response (from first response to progression), and overall survival.

2X-121 Phase 2 study in metastatic Breast Cancer (mBC)
2X-121 is an investigational, orally-available small molecule targeted inhibitor of Poly ADP ribose polymerase (PARP), a key enzyme involved in DNA damage repair in cancer cells. The drug candidate has a novel dual-inhibitory action against both PARP 1/2 and Tankyrase 1/2. The molecule is also active in P-glycoprotein expressing cells, suggesting it may overcome PARP inhibitor resistance. Patients will receive oral treatment with 600 mg 2X-121, as a single agent, in a 21-day cycle. The primary endpoint of this study is clinical benefit rate defined as complete response, partial response, or stable disease at greater than 24 weeks post-treatment using the RECIST criteria. Secondary endpoints include progression free survival, duration of response (from first response to progression), and overall survival.

Separate, targeted Phase 2 studies of 2X-121 are planned using the validated DRP biomarker in recurrent ovarian cancer, castration resistant prostate cancer, and pancreatic cancer to identify patients likely to respond to and benefit from treatment with the drug.

About the Drug Response Predictor – DRP Companion Diagnostic
Oncology Venture uses the Medical Prognosis Institute (MPI) multi gene DRP to select those patients who by the genetic signature of their cancer are found to have a high likelihood of responding to the drug. The goal is developing the drug for the right patients, and by screening patients before treatment the response rate can be significantly increased. The DRP method builds on the comparison of sensitive vs. resistant human cancer cell lines, including genomic information from cell lines combined with clinical tumor biology and clinical correlates in a systems biology network. DRP is based on messenger RNA from the patient’s biopsies.

The DRP platform, i.e. the DRP and the PRP tools, can be used in all cancer types and is patented for more than 70 anti-cancer drugs in the US. The PRP is used by MPI for Personalized Medicine. The DRP is used by Oncology Venture for drug development.

DRP is a registered trademark of Medical Prognosis Institute A/S.

On June 26, 2018 BerGenBio ASA (OSE:BGBIO) reported that on a top-line, preliminary basis, the first efficacy endpoint has been met in its Phase II clinical trial (BGBC008) evaluating bemcentinib, a first-in-class oral selective AXL inhibitor, in combination with the Merck & Co., Inc., Kenilworth, N.J., USA anti-PD-1 therapy KEYTRUDA (pembrolizumab) as a potential new treatment regimen for advanced non-small cell lung cancer (NSCLC)(Press release, BerGenBio, JUN 26, 2018, View Source [SID1234527463]) . The primary efficacy endpoint requires at least four patients (out of the first 22 treated patients) to achieve clinical responses when treated with the novel drug combination, defined as either complete or partial response, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).

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Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Immunotherapy has become a major component of the treatment of many cancers – patients who respond to immune checkpoint inhibitors like KEYTRUDA enjoy long-term disease control with excellent quality of life. Unfortunately, only a minority of lung cancer patients receiving KEYTRUDA monotherapy in second-line respond to treatment. The BGBC008 combination trial of bemcentinib with KEYTRUDA evaluates whether the addition of our selective AXL inhibitor will improve the outcome of immunotherapy.

"Clearing the first efficacy threshold in this ongoing Phase II trial is very encouraging and we intend to begin enrolment for Stage 2 of this study in which 24 further patients will be enrolled under the same protocol. Thus far, we are delighted to see activity in a number of patients receiving this novel treatment regimen. A particularly encouraging finding is that we see responses in patients who are negative for the PD-L1 biomarker, for whom KEYTRUDA monotherapy is not indicated. The second stage of the trial is intended to confirm activity and biomarker correlation in a larger group of patients – comprehensive analysis of the Phase II data will continue and will be presented at a future scientific conference.

"Successfully completing this important milestone further supports our belief in the potential of bemcentinib to become a cornerstone of cancer therapy. We look forward to sharing more details from our Phase II clinical programme during major clinical conferences in the coming months."

About the BGBC008 trial combining bemcentinib with KEYTRUDA (pembrolizumab) conducted in collaboration with Merck & Co., Inc.
Design
The BGBC008 trial is a Phase II multi-centre open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated, immunotherapy naïve, patients with advanced adenocarcinoma of the lung, the most common form of non-small cell lung cancer (NSCLC). The objective of the trial is to determine the anti-tumour activity of this novel drug combination and responses will be correlated with biomarker status (including AXL kinase and PD-L1 expression).

A pre-defined efficacy endpoint was set at four or more responses observed in the first 22 patients based on previously reported response rates to KEYTRUDA monotherapy in the second line setting in NSCLC.

Status June 2018
To date, 4 responses (partial responses as per RECIST v1.1) have been observed in the first 22 patients. A number of patients remain ongoing and are awaiting the confirmation of their best response.

Patients generally tolerated the novel drug combination well – no new safety events were reported from the combination of bemcentinib with KEYTRUDA at full dose.

A preliminary interim analysis of the trial (from 15 patients evaluable for response) was presented at ASCO (Free ASCO Whitepaper) 2018, where tumour shrinkage was observed in about half of the patients analysed to date. Results looked particularly promising in patients who did not express the PD-L1 biomarker, i.e. representing 1/3 of NSCLC patients, a group for whom KEYTRUDA monotherapy as a second line is not indicated.

For more information please access trial NCT03184571 at www.clinicaltrials.gov.

On June 26, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) and granted Priority Review for baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in patients 12 years and older (Press release, Hoffmann-La Roche, JUN 26, 2018, View Source [SID1234527464]). The FDA is expected to make a decision on approval by 24 December 2018. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

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"The severity of the recent flu season underscores the need for new options beyond currently available treatments, and if approved, baloxavir marboxil would be the first flu medicine with a novel proposed mechanism of action in nearly 20 years," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Baloxavir marboxil has been shown in clinical trials to decrease the duration of symptoms with one dose, and demonstrated a significant reduction in viral shedding in just one day. We look forward to working with the FDA during the review process."

Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the flu virus, including oseltamivir-resistant strains and avian strains (H7N9, H5N1).7,8,9 Unlike other currently available antiviral treatments, baloxavir marboxil is designed to inhibit the cap-dependent endonuclease protein within the flu virus, which is essential for viral replication.10,11

The NDA is based on results from the phase III CAPSTONE-1 study of a single dose of baloxavir marboxil compared with placebo or oseltamivir 75 mg, twice daily for five days, in otherwise healthy people with flu. Additionally, results from a placebo-controlled phase II study in otherwise healthy people with the flu is included as supporting data in the NDA.

About CAPSTONE-1
CAPSTONE-1 is a phase III multicentre, randomised, double-blind, placebo-controlled study that evaluated the efficacy and safety of baloxavir marboxil in 1,436 people in the United States and Japan. The primary endpoint of the study was time to alleviation of symptoms (TTAS), and important secondary endpoints were time to resolution of fever, time to cessation of viral shedding and the proportion of participants positive for influenza virus titre, or virus levels in the body, by time point. The study found the following results:

Baloxavir marboxil met its primary and secondary endpoints compared to placebo:
Significantly reduced the duration of flu symptoms by more than one day (median time 53.7 hours versus 80.2 hours; p<0.0001);
Significantly reduced the duration of fever by nearly a day (median time 24.5 hours versus 42.0 hours; p<0.0001);
Significantly reduced the length of time viruses continued to be released from the body (median time of viral shedding; 24.0 hours versus 96.0 hours; p<0.0001);
Significantly reduced the levels of virus in the nose and throat from 24 hours through 120 hours.
Similar efficacy results were seen between baloxavir marboxil and oseltamivir in relation to duration of symptoms and fever reduction, but significant differences were observed in time to cessation of viral shedding favouring baloxavir marboxil:
No significant reduction in duration of symptoms (median time 53.5 hours versus 53.8 hours; p=0.7560);
No significant reduction in time to resolution of fever (median time 24.4 hours versus 24.0 hours; p=0.9225);
Significantly reduced the length of time the virus continued to be released from the body (viral shedding; 24.0 hours versus 72.0 hours; p<0.0001);
Significantly reduced the levels of virus in the nose and throat at 24 hours and 72 hours.
Baloxavir marboxil was well-tolerated and had a numerically lower overall incidence of adverse events (20.7%) reported compared with placebo (24.6%) or oseltamivir (24.8%). The most common adverse events reported were diarrhoea (3.0%), bronchitis (2.6%), nausea (1.3%) and sinusitis (1.1%), and all of these adverse events occurred at a lower frequency than placebo.

About baloxavir marboxil
Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the influenza ("flu") A and B viruses, including oseltamivir-resistant strains and avian strains (H7N9, H5N1).7,8,9 Unlike other currently available antiviral treatments, baloxavir marboxil is the first in a new class of antivirals designed to inhibit the cap-dependent endonuclease protein within the flu virus, which is essential for viral replication.

Baloxavir marboxil is being studied in an ongoing phase III development program including paediatric populations with influenza. Data from the global phase III study (CAPSTONE-2) in patients 12 years and older with a high risk of complications from influenza, as defined by the Centers for Disease Control and Prevention (CDC), will be shared at a later date.

Baloxavir marboxil was discovered by Shionogi & Co., Ltd. and is being developed globally by the Roche Group (which includes Genentech in the U.S.) and Shionogi & Co., Ltd. Under the terms of this agreement, Roche holds worldwide rights to baloxavir marboxil excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd. Baloxavir marboxil was approved in February 2018 by the Japanese Ministry of Health, Labour and Welfare for the treatment of influenza types A and B in adult and paediatric patients and is being commercialised in Japan and marketed under the brand name Xofluza.