On October 17, 2017 Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) and AstraZeneca PLC (“AstraZeneca”) reported preliminary safety and clinical activity data of savolitinib when given in combination with either Tagrisso (osimertinib) or Iressa (gefitinib) in two Phase Ib/II proof-of-concept trials conducted in patients with epidermal growth factor receptor (“EGFR”) mutation-positive (“EGFRm”) non-small cell lung cancer (“NSCLC”) with MET-amplification who had progressed following first-line treatment with an EGFR inhibitor (Press release, Hutchison China MediTech, OCT 17, 2017, http://www.chi-med.com/savo-in-2l-met-amp-lung-cancer/ [SID1234521000]). In both trials, the addition of savolitinib (600mg, once daily), an investigational selective inhibitor of mesenchymal epithelial transition factor (“c-MET”) receptor tyrosine kinase, to Tagrisso (80mg, once daily) or Iressa (250mg, once daily) demonstrated preliminary anti-tumor activity. The data were shared in two oral presentations at the International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer (“WCLC”) in Yokohama, Japan, October 15 to 18, 2017.

Dr. Myung-Ju Ahn, Department of Hematology & Oncology, Samsung Medical Center, Seoul, South Korea, said, “Secondary resistance mechanisms often emerge during treatment with mutation-targeted medicines, leading to disease progression. The data presented at WCLC demonstrate the potential of utilizing savolitinib in c-MET-driven lung cancers to address resistance challenges.”

Susan Galbraith, Head of Oncology, AstraZeneca Research and Early Development, said, “We are committed to developing innovative medicines to overcome the key drivers of cancer mechanisms of resistance and are strategically focused on developing effective combinations. The latest results for savolitinib in combination with osimertinib and gefitinib support our approach in collaboration with Chi-Med.”

Preliminary Results for Savolitinib in Combination with Tagrisso[i]
In the Phase Ib/II proof-of-concept TATTON trial in patients with EGFRm advanced NSCLC with MET-amplification confirmed locally or centrally, early data on safety and anti-tumor activity for savolitinib in combination with Tagrisso were presented. In 66 patients treated, the most common all-causality adverse events (“AEs”) were nausea (44%), vomiting (35%), fatigue (30%), and decreased appetite (30%), which were consistent with the known safety profiles of savolitinib and Tagrisso.

Preliminary data showed partial response according to Response Evaluation Criteria in Solid Tumors (“RECIST”) 1.1 criteria in 33% of patients previously treated with third-generation T790M-directed EGFR inhibitors, including Tagrisso (n=30). In patients who had progressed after prior treatment with a first- or second-generation EGFR inhibitor, 61% of T790M mutation negative patients (n=23) had a partial response, while 55% of T790M mutation positive patients (n=11) had a partial response.

In those patients where MET-positive status was determined centrally, preliminary data showed partial response in 28% of patients previously treated with T790M-directed EGFR inhibitors (n=25). In patients who had progressed after prior treatment with a first- or second-generation EGFR inhibitor, 53% of T790M mutation negative patients (n=15) had a partial response, while 57% of T790M mutation positive patients (n=7) had a partial response.

The presentation will be available at www.chi-med.com/ph2-savo-plus-tagrisso-nsclc/.

Preliminary data for Savolitinib in Combination with Iressa[ii]
Data from the Phase Ib/II proof-of-concept trial assessing savolitinib in combination with Iressa in patients in China with EGFRm advanced NSCLC with centrally confirmed MET-amplification who had progressed following EGFR inhibitor therapy were also reported. The most common AEs independent of causality in 51 patients treated were vomiting (39%), increased alanine aminotransferase (ALT) (37%), increased aspartate aminotransferase (AST) (35%), nausea (35%), and rash (35%). These results were consistent with the known safety profiles of savolitinib and Iressa.

Preliminary results showed that 31% of patients had a partial response according to RECIST 1.1 criteria, of which 52% of T790M negative patients (n=23) and 9% of T790M positive patients (n=23) achieved a partial response.

The presentation will be available at www.chi-med.com/ph2-savolitinib-plus-iressa-nsclc/.

Mr. Christian Hogg, Chief Executive Officer of Chi-Med, said, “MET-amplification impacts a meaningful proportion of patients with EGFRm NSCLC who experience disease progression following treatment with a tyrosine kinase inhibitor in the first or second-line setting. Among patients with this difficult-to-treat resistance mechanism, there is a clear unmet medical need.”

About Savolitinib
Savolitinib (AZD6094/HMPL-504) is a potential first-in-class selective inhibitor of c-MET (also known as mesenchymal epithelial transition factor) receptor tyrosine kinase, an enzyme which has been shown to function abnormally in many types of solid tumors. It was developed as a potent and highly selective oral inhibitor specifically designed to address issues observed in the clinic with other selective c-MET inhibitors, such as renal toxicity.

Savolitinib was discovered by Chi-Med and is being developed in collaboration with AstraZeneca. Savolitinib is currently being studied in multiple tumor types worldwide including kidney, lung and gastric cancers, both as a monotherapy and in combination with other targeted and immunotherapy agents.

On October 17, 2017 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported the oral presentation of interim data from a Phase 2 clinical study evaluating poziotinib in EGFR Exon 20 Mutant Non-Small-Cell Lung Cancer (NSCLC) by scientists from the MD Anderson Cancer Center which was presented in Yokohama, Japan, October 15-18, 2017 (Press release, Spectrum Pharmaceuticals, OCT 17, 2017, View Source [SID1234520994]). The Company will hold a conference call tomorrow, October 18th, at 8:30 a.m. EDT/5:30 a.m. PDT with Dr. John Heymach, M.D., Ph.D., Chairman, Professor, and David Bruton Junior Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, to discuss his study results.

“These data are remarkable for NSCLC patients with exon 20 insertion mutations,” said John Heymach, M.D., Ph.D., The University of Texas MD Anderson Cancer Center. “These patients currently have a poor prognosis, single-digit response rate on first generation tyrosine kinase inhibitors (TKI’s), and a PFS of about two months. What is truly noteworthy is that all 11 study patients who received poziotinib at a 16mg daily dose and have reached their first scan, have seen some level of tumor shrinkage. Interestingly, we have also seen evidence of CNS activity. Toxicities have included rash, diarrhea, paronychia, and mucositis consistent with those previously described for poziotinib and other TKI’s, which led to dose reduction in 55% of the patients. We believe that poziotinib specifically inhibits EGFR with exon 20 insertion mutations because it overcomes steric hindrance caused by exon 20 insertions, due to its smaller size and flexibility. To date poziotinib has shown promising results in patients with exon 20 insertion mutations and we are fortunate to be leading the efforts in the continuing development of this product.”

“We are greatly encouraged with the clinical data emerging from poziotinib and plan to pursue its clinical development expeditiously and aggressively,” said Rajesh C. Shrotriya, M.D., Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. “In the near future, we plan to discuss the regulatory pathway for poziotinib with the FDA. At the same time, we are embarking upon an overall strategy for global clinical development and regulatory filings. With three promising drugs in late-stage development, Spectrum’s pipeline has never been as exciting and our prospects never as bright.”

Conference Call

Wednesday, October 18, 2017 @ 8:30 a.m. Eastern/5:30 a.m. Pacific

Domestic: (877) 837-3910, Conference ID# 86093351

International: (973) 796-5077, Conference ID# 86093351

For interested individuals unable to join the call, a replay will be available from October 18, 2017 @ 11:30 a.m. ET/8:30 a.m. PT through October 28, 2017, until 11:30 a.m. ET/8:30 a.m. PT.

Domestic Replay Dial-In #: (855) 859-2056, Conference ID# 86093351

International Replay Dial-In #: (404) 537-3406, Conference ID# 86093351

This conference call will also be webcast. Listeners may access the webcast, which will be available on the investor relations page of Spectrum Pharmaceuticals’ website: www.sppirx.com on October 18, 2017, at 8:30 a.m. Eastern/5:30 a.m. Pacific.

About Poziotinib

Poziotinib is a novel, oral pan-HER inhibitor that irreversibly blocks signaling through the Epidermal Growth Factor Receptor (EGFR, HER) Family of tyrosine-kinase receptors, including HER1 (erbB1; EGFR), HER2 (erbB2), and HER4 (erbB4), and importantly, also HER receptor mutations; this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small-cell lung cancer (NSCLC), breast cancer, and gastric cancer. Spectrum received exclusive license to develop, manufacture, and commercialize worldwide excluding Korea and China from Hanmi Pharmaceuticals. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumor indications.

About the WCLC

The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting over 6,000 researchers, physicians, and specialists from more than 100 countries. The goal is to disseminate the latest scientific achievements; increase awareness, collaboration, and understanding of lung cancer; and to help participants implement the latest developments across the globe. Organized under the theme of “Synergy to Conquer Lung Cancer,” the conference covers a wide range of disciplines and unveils several research studies and clinical trial results. For more information, visit View Source

On October 17, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported updated results from its clinical trials, including the STARTRK-2 trial, of entrectinib – an investigational, CNS-active, potent, and selective tyrosine kinase inhibitor being developed for tumors that harbor NTRK fusions or ROS1 fusions (Press release, Ignyta, OCT 17, 2017, View Source [SID1234520990]). In this interim analysis, entrectinib demonstrated a 78% confirmed ORR (by Investigator; 95% CI: 60.0, 90.7) and a 69% confirmed ORR (by Blinded Independent Central Review, or BICR; 95% CI: 50.0, 83.9) in 32 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbored ROS1 fusions.

Entrectinib demonstrated compelling durability in these patients, with a median duration of response (mDOR) of 28.6 months (by BICR; 95% CI: 6.8, 34.8; median follow-up of 12.9 months) and a median progression free survival (mPFS) of 29.6 months (by BICR; 95% CI: 7.7, 36.6; median follow-up of 8.5 months). Of the patients evaluated, 11 had CNS metastases at baseline as assessed by Investigator, and 83 percent (5 out of 6; by BICR) of the patients with measurable CNS metastases at presentation had confirmed intracranial RECIST responses to treatment with entrectinib. The data were presented today in an oral presentation at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan.

“Based on these data, we believe that entrectinib has the potential to be a best-in-class therapeutic option as a first-line targeted therapy for patients with ROS1-positive NSCLC”
Tweet this
“Based on these data, we believe that entrectinib has the potential to be a best-in-class therapeutic option as a first-line targeted therapy for patients with ROS1-positive NSCLC,” said Jonathan Lim, M.D., chairman and CEO of Ignyta. “The extended duration of response and progression free survival times observed in these interim data are particularly compelling, and we believe may be driven by entrectinib’s CNS activity. Entrectinib was designed to cross the blood-brain barrier, allowing it to both address preexisting CNS lesions and have the potential to prevent or delay the onset of metastases to the brain, a common site of progression, particularly in NSCLC.”

Safety was consistent with previous studies of entrectinib. With over 200 patients treated at the recommended phase 2 dose, most adverse events (AEs) were Grade 1-2 and reversible, and only 3 percent of patients discontinued from the study due to treatment-related AEs (TRAEs). The most common TRAEs were dysgeusia (38%), fatigue (29%), constipation (23%), dizziness (23%), and increased weight (19%). The most common Grade 3 TRAEs were increased weight (5%), anemia (4%), and fatigue (3%). There were no Grade 4 events occurring in greater than one percent of patients and no Grade 5 TRAEs.

“ROS1 fusions occur in approximately two percent of all cases of NSCLC and, given the propensity for these tumors to metastasize to the brain, the CNS activity of entrectinib is a critical differentiating feature of the compound and may be contributing to the impressive duration and progression free survival it has demonstrated thus far,” said Myung-Ju Ahn, Professor in the Department of Hematology and Oncology at the Samsung Medical Center in Seoul Korea and study author.

In addition to these data in ROS1-positive NSCLC, entrectinib has demonstrated promising preliminary antitumor activity across NTRK-positive solid tumors, an indication for which entrectinib has received breakthrough therapy designation (BTD) from the U.S. Food and Drug Administration (FDA) and PRIME designation from the European Medicines Agency (EMA). Based on recent guidance from the FDA, the company is on track for dual NDA submissions in both the NTRK tissue-agnostic and the ROS1-positive NSCLC indications in 2018.

A conference call and live webcast will be held on October 18, 2017, at 8:00 a.m. Eastern Time to discuss the data presented, as well as the comprehensive entrectinib program. To participate in the conference call, please dial 800-946-0716 (U.S.) or 719-325-4934 (international) and provide Conference ID 7994148. To access the live webcast, go to View Source

About Entrectinib

Entrectinib is an investigational, CNS-active, potent, and selective small molecule tyrosine kinase inhibitor of the TRK (tropomyosin receptor kinase) family of tyrosine kinase receptors (TRKA, TRKB and TRKC) and ROS1 proteins, which is in a Phase 2 clinical study and two Phase 1 clinical studies in molecularly defined adult patient populations for the treatment of solid tumors, and a Phase 1/1b clinical study in pediatric patients with advanced solid tumor malignancies.

About STARTRK-2

STARTRK-2 is an open-label, multicenter, global Phase 2 basket study of entrectinib for the treatment of patients with locally advanced or metastatic solid tumors that harbor NTRK1/2/3, ROS1, or ALK gene rearrangements. The basket design screens patient tumor samples for the relevant targets to take full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types and molecular targets.

About Ignyta, Inc.

Blazing a New Future for Patients with Cancer

At Ignyta, we work tirelessly on behalf of patients with cancer to offer potentially life-saving, precisely targeted therapeutics (Rx) guided by diagnostic (Dx) tests. Our integrated Rx/Dx strategy allows us to enter uncharted territory, illuminating the molecular and immunological drivers of cancer and quickly advancing treatments to address them. This approach embraces even those patients with rare cancers, who have the highest unmet need and who may otherwise not have access to effective treatment options. With our pipeline of potentially first-in-class or best-in-class precision medicines, we are pursuing the ultimate goal of not just shrinking tumors, but eradicating cancer relapse and recurrence in precisely defined patient populations.

For more information, please visit: www.ignyta.com.

About the WCLC

The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting over 6,000 researchers, physicians and specialists from more than 100 countries. The goal is to disseminate the latest scientific achievements; increase awareness, collaboration and understanding of lung cancer; and to help participants implement the latest developments across the globe. Organized under the theme of “Synergy to Conquer Lung Cancer,” the conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit View Source