On June 6, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that updated data from the ongoing Phase 1 trial of FPA144 was featured today in an oral presentation during the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Five Prime Therapeutics, JUN 6, 2016, View Source [SID:1234513068]). Dr. Jeeyun Lee from the Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, gave the presentation, titled Antitumor Activity and Safety of FPA144, an ADCC-enhanced, FGFR2b Isoform-Selective Monoclonal Antibody, in Patients with FGFR2b+ Gastric Cancer and Advanced Solid Tumors (Abstract 2502). The presentation is available on the Five Prime website: View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Part 1 of the trial evaluated escalating doses of FPA144 as a single agent in 27 patients, 19 with advanced solid tumors in Part 1a and 8 with advanced gastric cancer in Part 1b, including 6 with FGFR2b-overexpressing tumors. Enrollment is underway in Part 2 of the trial, evaluating the safety, pharmacokinetics (PK) and efficacy (objective response rate and duration of response) of biweekly 15 mg/kg infusions of FPA144 across multiple cohorts: gastric cancer patients whose tumors have high, moderate and low levels of FGFR2b protein overexpression and gastric cancer patients whose tumors do not have FGFR2b protein overexpression. Five Prime plans to expand the scope of this trial further by the end of 2016 to include a cohort of patients with a tumor type (other than gastric) that overexpresses FGFR2b.

Safety findings presented in this update are consistent with initial data presented during the ASCO (Free ASCO Whitepaper) Gastrointestinal Symposium in January 2016. Data across 40 patients in the full safety population of this trial (all gastric and solid tumor patients receiving any portion of at least one dose of FPA144) suggest that FPA144 has an acceptable safety profile in doses up to 15 mg/kg:

No dose-limiting toxicities (DLTs); maximum-tolerated dose (MTD) was not reached
No treatment-related serious adverse events (SAEs); 17 reported SAEs across 9 patients
No treatment-related adverse events (AEs) resulting in treatment discontinuation
No treatment-related hyperphosphatemia or retinal toxicity (differentiated from small molecule kinase inhibitors targeting FGF receptor tyrosine kinases)
The most common treatment-related AEs ( > 5%) were all grades 1 or 2: fatigue (22.5%), nausea (20%) and vomiting (12.5%)
One transient treatment-related Grade 3 AE of decreased neutrophil count
Comparable safety between gastric cancer patients and full safety population

FPA144 monotherapy demonstrated early evidence of anti-tumor efficacy in the 9 gastric cancer patients with FGFR2b protein overexpression (6 from Part 1b of the trial; 3 from Part 2) that were available for analysis as of the April 1, 2016 data cutoff. These patients were heavily pre-treated, having received between 1 and 6 prior therapies with a median of 2 prior therapies. The activity observed includes:

3 confirmed partial responses (PRs) out of 9 gastric cancer patients treated (33%) (one of these three PRs confirmed after the April 1, 2016 data cutoff)
7 of 9 gastric cancer patients with disease control (3 PRs + 4 stable disease), disease control rate (DCR) = 77%
12-week progression-free survival (PFS) in 6 of 9 gastric cancer patients (67%)
Median duration of treatment of 112 days (range 42-182 days), with 2 of 9 gastric cancer patients still on study
1 complete response (CR) in a patient with metastatic bladder cancer
In addition to the 3 PRs noted above, there was an additional unconfirmed PR in the 10th gastric cancer patient with FGFR2b protein overexpression (the 4th patient in the 15 mg/kg cohort). This 10th patient’s scan became available after the data cutoff of April 1, 2016, and the patient remains on treatment.

"The data suggest that FPA144 is an active drug that warrants further clinical development. The initial single-agent efficacy and safety data seen during the dose escalation portion of the study is encouraging," said Dr. Charles Fuchs, Director of the Center for Gastrointestinal Cancer, Dana Farber Cancer Institute. "Patients with advanced gastric cancer have a significant unmet medical need, and the literature suggests that those with tumors that overexpress FGFR2b have an even worse prognosis. New treatments options are needed for these patients."

"We are pleased with the data from this ongoing trial," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "The data we have observed in this trial suggest that FPA144 has an acceptable safety profile and can be dosed biweekly. FPA144 monotherapy also showed evidence of clinical activity in the first nine FGFR2b+ gastric cancer patients that were available for analysis, with a disease control rate of 77% and a 12-week progression free survival of 67%. We were also pleased to see an unexpected complete response in a patient with bladder cancer in part 1a of the trial. We look forward to continuing the study and to further exploring FPA144 in gastric cancer with varying levels of FGFR2b protein overexpression as well as additional FGFR2b+ tumors."

About the FPA144 Phase 1 Trial
Parts 1a and 1b of the Phase 1 study evaluated the safety and pharmacokinetics (PK) of escalating doses of FPA144 in 27 patients with solid tumors, including gastric cancer patients. Enrollment is underway in Part 2 of the trial, evaluating the safety, PK and efficacy (response rate and duration of response) of biweekly 15 mg/kg infusions of FPA144 across multiple cohorts: gastric cancer patients with high, moderate and low levels of FGFR2b protein overexpression, FGFR2b- gastric cancer patients, and FGFR2b+ patients with other tumor types. Up to 30 patients may be enrolled in each tumor setting. Tumors will be biopsied pre- and post-treatment in order to determine levels of FGFR2b protein overexpression and FGFR2 gene amplification, and to detect PD-L1 and immune infiltrate changes within the tumor. Testing for FGFR2b protein overexpression is being conducted centrally, using a proprietary immunohistochemistry assay.

About FPA144
FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

FPA144 is designed to block tumor growth through two distinct mechanisms. First, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells and T cells. Second, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. When combined with PD-1 blockade, FPA144 has shown an additive effect in tumor growth inhibition in preclinical models. Five Prime retains global development and commercialization rights to FPA144.

On June 6, 2016 Kite Pharma, Inc. (Nasdaq:KITE) ("Kite") reported results from SCHOLAR-1 (Retrospective Non-Hodgkin Lymphoma Research), the first, large, systematic, multi-institutional, patient-level meta-analysis of outcomes from 635 patients with chemorefractory diffuse large B-cell lymphoma (DLBCL) (Press release, Kite Pharma, JUN 6, 2016, View Source [SID:1234513046]). The study showed that patients with chemorefractory disease – defined as disease that does not respond to treatment with a chemotherapy-based regimen or has relapsed less than 12 months after autologous stem cell transplant (ASCT) – have consistently poor outcomes regardless of refractory subgroup, line of therapy, and disease stage. The study will be presented today at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (abstract #7516).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These study results are important because they confirm the regrettable outcomes that have been observed in the clinical setting for people with this difficult-to-treat form of DLBCL," said Dr. John Kuruvilla, Associate Professor of Medicine at the University of Toronto, and a clinical investigator in the Department of Medical Oncology at Princess Margaret Cancer Centre in Toronto. "While DLBCL is considered curable with initial chemotherapy-based treatment, patients with chemorefractory DLBCL have limited-to-no treatment options and historically poor outcomes, underscoring the significant need for new therapies."

According to the American Cancer Society, non-Hodgkin lymphoma (NHL) accounts for about four percent of all cancers in the United States, making it one of the most common cancers diagnosed. DLBCL is the most common form of the disease, accounting for one out of every three cases of NHL.1 It is estimated that approximately 26,000 people will be diagnosed with DLBCL in the United States in 2016.

"Little is known about the outcomes of people with chemorefractory DLBCL, leaving a large gap in the treatment landscape. These data help to track the course of the disease and provide an important historical benchmark for studies in this patient population," said David Chang, M.D., Ph.D., Kite’s Executive Vice President, Research and Development, and Chief Medical Officer. "We are proud to partner with clinicians, scientists and researchers at MD Anderson Cancer Center, the Mayo Clinic, the University of Iowa, the Canadian Cancer Trials Group, and LYSARC (The Lymphoma Academic Research Organisation) to help establish a better understanding of the disease to determine how best to treat patients with chemorefractory DLBCL."

About the SCHOLAR-1 Study

The SCHOLAR-1 (Retrospective Non-Hodgkin Lymphoma Research) is a retrospective analysis of patients with chemorefractory DLBCL comprised of data from Phase 3 studies from the Canadian Cancer Trials Group (CCTG LY.12 Study) and LYSARC (CORAL Study) and large retrospective databases including from the MD Anderson Cancer Center, Mayo Clinic and University of Iowa Specialized Programs of Research Excellence (SPORE).

In the study, 635 patients with chemorefractory DLBCL were eligible for evaluation based on the following criteria: DLBCL defined as progressive disease as best response to chemotherapy; or stable disease as best response to chemotherapy (received at least 4 cycles of first-line or 2 cycles of later-line therapy); or relapse ≤ 12 months of ASCT. Patients must have received an anti-CD20 monoclonal antibody (unless CD20 negative) and an anthracycline as one of their prior regimens.

Results to be presented at ASCO (Free ASCO Whitepaper) showed:

The overall response rate (ORR; complete response plus partial response) across all 635 patients was 26% (165/635) with only 8% (51/635) achieving a complete response, showing no signs of the disease
The response rates were consistent ranging from 21% to 31% ORR and 2% to 15% complete response (CR) across centers and data sets
Median overall survival was 6.6 months and consistent across subgroups including refractory status, stage of disease and line of therapy

On June 6, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported new data in two presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 that underscore the critical importance of integrating comprehensive genomic profiling into clinical care programs for the treatment of advanced breast cancer (Press release, Foundation Medicine, JUN 6, 2016, View Source [SID:1234513069]). Data presented from two separate studies showed:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Molecular information elucidated from FoundationOne led physicians to change their recommended course of therapy for 41 percent of patient cases;
77 percent of patients profiled with FoundationOne harbored an alteration matched to an FDA-approved therapy;
98 percent of patients with advanced breast cancer had genomic alterations that matched therapeutics being studied in clinical trials; and
20 percent of advanced breast cancers possess high tumor mutational burden, suggesting a potential role for FoundationOne as a predictive biomarker for immune checkpoint inhibition.
"It’s no longer sufficient to classify or treat breast cancer as a single disease, and we must continue to acknowledge and understand its vast, complex genomic variability in order to provide individuals with every opportunity for improved outcomes," said Vincent Miller, M.D., chief medical officer, Foundation Medicine. "In a striking example of the importance of genomic information in breast cancer treatment, data presented at ASCO (Free ASCO Whitepaper) show that comprehensive genomic profiling led to physician-recommended therapy changes, matches with FDA-approved therapeutic agents that otherwise may have been overlooked or missed, and links to clinical trials for investigational targeted agents. This data is significant for the approximately 40,000 individuals in the United States who present with metastatic breast cancer annually, and it underscores opportunity with precision medicine to improve outcomes by matching patients with the right therapies."

Key Data Highlights:

The poster "Decision impact analysis of comprehensive genomic profiling (CGP) in advanced breast cancer: A prospective study," presented by Raquel E. Reinbolt, M.D., assistant professor, internal medicine, college of medicine, The Ohio State University, presented data that demonstrated that comprehensive genomic profiling in advanced breast cancer provides therapy or clinical trial recommendations for more than 70 percent of patients screened. A prospective, single center, single arm study enrolled advanced breast cancer patients who were within 10 weeks of starting therapy and who had an estimated survival of ≥ 3 months. Key findings include:

Comprehensive genomic profiling noted the existence of an FDA approved drug for 77 of 83 patients, with everolimus (n=72), temsirolimus (n=70), ponatinib (n=23) and pazopanib (n=20) being the most frequently selected by physicians
At least one clinical trial was identified for 98 percent of patients
A change in therapy was recommended by the treating physician for 34 of 83 patients (41 percent), and of these, 17 patients (50 percent) pursued the suggested treatment
A second poster "Biomarkers of Immune Checkpoint Inhibitor Response in Metastatic Breast Cancer: PD-L1 Protein Expression, PD-L1 Gene Amplification and Total Mutational Burden," presented by Jeffrey S. Ross, M.D., medical director, Foundation Medicine and Chair of the Department of Pathology, Albany Medical College, studied potential predictive biomarkers for immune checkpoint inhibitors in more than 6,000 breast cancer tumor samples at Foundation Medicine, and 84 breast cancer cases at Albany Medical Center. In the study, comprehensive genomic profiling using FoundationOne was performed on a cohort of 6,751 metastatic breast cancer tumor samples which were also evaluated for tumor mutational burden. PD-L1 expression detected by immunohistochemistry was used to predict patient survival in the 84 case Albany Medical Center cohort.

Key findings include:

PD-L1 protein expression in infiltrating immunocytes was found to be a significant favorable prognostic factor, which significantly correlated with increased overall survival whereas lack of PD-L1 staining in both tumor cells and immunocytes was a significant adverse prognostic factor associated with decreased patient survival
PD-L1 gene amplification was identified in only 57 of 6,751 (0.1 percent) metastatic breast cancer tumor samples, correlating with the potential for response to immune checkpoint inhibitors
High tumor mutational burden was found in 1,351 of 6,643 (20 percent) metastatic breast cancer cases underscoring the potential for further studies measuring tumor mutational burden with FoundationOne to identify breast cancer patients as candidates for immunotherapy
Breast cancer is the most common type of cancer among women in the United States, excluding non-melanoma cancers of the skin. The American Cancer Society estimates that approximately 246,660 women will be diagnosed with breast cancer in 20161. Although the majority of these patients will be cured of their disease in the primary treatment setting, the more than 40,000 cases of relapsed and metastatic breast cancer make this disease the second leading cause of death from cancer in American women2. The matching of patients with advanced breast cancer to personalized therapies holds significant promise to improving clinical outcomes for these patients.

On June 6, 2016 Aprea AB, a privately held, clinical-stage biopharmaceutical company developing novel anticancer therapies targeting the tumor suppressor protein p53, reported clinical data from the Phase Ib part of the ongoing PiSARRO Phase Ib/II trial in collaboration with the European Network for Translational Research in Ovarian Cancer (EUTROC) (Press release, Aprea, JUN 6, 2016, View Source [SID:1234513118]). Aprea’s PiSARRO trial is investigating the safety and efficacy of APR-246 in combination with carboplatin and pegylated liposomal doxorubicin (PLD) in patients with relapsed high-grade serous ovarian cancer. Results presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) showed:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

APR-246 can be combined with standard chemotherapy at relevant doses, allowing the highest tested dose to be selected for continuing the study in a randomized Phase II trial.
All 21 patients treated in the study that are evaluable according to RECIST criteria have stable disease or better. In addition, 15 out of 18 evaluable patients had a GCIG CA-125 (tumor antigen biomarker) response after three treatment cycles. Overall response rate (GCIG or RECIST) was 18/24 (75%).
APR-246 showed linear pharmacokinetics with no accumulation and low intra patient variability and no indication of interaction between APR-246 and chemotherapy, supporting the combination of APR-246 with carboplatin and doxorubicin at relevant doses.
The main related treatment-emergent Grade 3-4 adverse events have been neutropenia, anemia and vomiting. The most frequent treatment-emergent adverse events have been low-grade gastrointestinal (nausea/vomiting), central nervous system (dizziness) and hematological (neutropenia and thrombocytopenia) events. The hematological side effects can be attributed to the chemotherapy, although a contribution from the addition of APR-246 cannot be ruled out at this time. No new safety concerns have emerged in the study.
Prof. Charlie Gourley, Chair of Medical Oncology and Honorary Consultant in Medical Oncology at the University of Edinburgh, said of the results: "APR-246 is an extremely exciting new agent because it targets tumors with mutant forms of the p53 gene, which is the gene most frequently altered in human cancer. This study shows that APR-246 can be successfully combined with standard chemotherapy for ovarian cancer with minimal additional toxicity. The percentage of patients whose cancer responded to this treatment regime was encouraging and we look forward to validating these findings in a larger clinical trial."

Dr. Mikael von Euler, Chief Medical Officer of Aprea, said: "We are very pleased with the results of the Phase Ib trial and to be able to move this exciting drug forward into a randomized Phase II trial in the third quarter of this year. It is especially important that the patients who have more difficult-to-treat disease seem to get as much benefit as those with less aggressive disease. The current safety profile combined with the evidence of clinical activity suggests that APR-246 might become a very important drug for patients with ovarian cancer. Furthermore, the mechanism suggests that APR-246 might have relevance in other tumor types and we look forward to pursing those opportunities."

About p53 and APR-246

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anticancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 has been shown to reactivate mutant p53 protein – by reconverting mutant p53 into wild-type p53 conformation and function – and thereby induce programmed cell death in human cancer cells. APR-246 has demonstrated compelling pre-clinical antitumor activity in a wide variety of solid and hematological (blood) tumors, including ovarian cancer, small cell lung cancer, esophageal cancer and AML (acute myeloid leukemia), among others. Additionally, strong synergy has been seen with both traditional anticancer agents, such as chemotherapy, as well as newer mechanism-based anticancer drugs. In addition to pre-clinical testing, a Phase I clinical study has been completed, demonstrating a favorable safety profile and both biological and clinical responses in hematological tumors with mutations in the p53 gene. APR-246 is currently in a Phase Ib/II clinical trial in patients with high-grade serous ovarian cancer. The Phase Ib part has completed. In the Phase II clinical study, Aprea will enroll up to 400 ovarian cancer patients in Europe and the US. Patients will be randomized between carboplatin and pegylated liposomal doxorubicin with or without APR-246; the primary endpoint for the study is progression-free survival (PFS). The company is also expecting to begin additional clinical studies of APR-246 in other cancer indications.

On June 5, 2016 Mirati Therapeutics, Inc. (NASDAQ: MRTX) reported an update on three current ongoing clinical programs in patients with non-small cell lung cancer (NSCLC) and other solid tumors (Filing, 8-K, Mirati, JUN 6, 2016, View Source [SID:1234513142]).

"We are making significant progress in the development of our pipeline as our ongoing clinical programs are showing meaningful results," said Charles M. Baum, M.D., Ph.D., president and CEO. "We have confirmed responses including sustained activity in our glesatinib program, and encouraging signs of early efficacy from sitravatinib. These data demonstrate our ability to advance our targeted oncology drug candidates through our differentiated development approach. Today we also announced the start of our mocetinostat combination trial, our first in immuno-oncology. We are excited about the potential to deliver meaningful data points on all three of our clinical programs in 2016 and into 2017."

Glesatinib Program Update

Glesatinib Phase 1b Trial

As of May 20, 2016, 28 patients with MET and AXL alterations were enrolled in the Phase 1b trial across multiple tumor types, including 22 NSCLC patients. A majority of these patients were heavily pretreated with multiple lines of prior therapy including radiation and/or surgery. Eleven of the NSCLC patients had genetic driver alterations comparable to the criteria in our ongoing Phase 2 trial, including two NSCLC patients with MET amplifications, eight NSCLC patients with MET exon14 deletion mutations, and one NSCLC patient with AXL amplification.

The results demonstrate tumor regression in the majority of patients including confirmed responses to glesatinib:

· 3 of 11 NSCLC patients had partial responses (PRs) confirmed per RECIST, including patients with a MET amplification, MET exon14 deletion mutation and AXL amplification
· Patients with confirmed responses were on study for 39 weeks, 23 weeks and 56 weeks, with the 23 and 56 week patients continuing on study
· Tumor regression was seen in 10 of the 11 patients, three of which had confirmed PRs

During the course of the Phase 1b trial, the majority of the NSCLC patients (nine of 11) experienced dose reductions and/or dose interruptions. These events may have resulted in decreased exposure levels needed to fully inhibit MET throughout the treatment cycle.

Of the nine patients whose doses were reduced during the trial, two had a second dose reduction; four patients had dose interruptions and three had multiple dose interruptions while on study. Of the patients no longer on trial, five discontinued due to disease progression, two were related to AEs (one incidence of nausea and vomiting and one diarrhea) and one patient withdrew consent.

The dose reductions and interruptions were due primarily to episodes of diarrhea, potentially associated with the original miglyol (an oil-based excipient similar to castor oil) formulation of glesatinib administered during the trial, which may have contributed to or exacerbated diarrhea.

A new formulation of glesatinib is being implemented in the ongoing Phase 2 trial to reduce dose reductions and interruptions and to optimize exposure levels throughout the treatment regimen. The new spray-dried dispersion (SDD) formulation of glesatinib was evaluated in a dose escalation arm of the Phase 1b study and a recommended Phase 2 dose of 750mg BID was established.

The patient with a MET exon14 deletion and confirmed PR has shown significant tumor regression as well as improved tolerability after moving to the new formulation at a dose of 500mg BID. Following two full cycles of treatment with the new formulation, the patient experienced a deepening PR, from 45% to 66%, and remains on study.

Data from the Phase 1b trial has shown the SDD formulation to have several advantages including: (i) fewer tablets per dose; (ii) better relative bioavailability than the original formulation supporting full target inhibition; (iii) improved tolerability; and (iv) manufacturing advantages.

"We believe that the combination of improved tolerability and bioavailability of the new formulation will allow patients to remain on the intended dose, extend the duration of treatment and possibly increase response rates," continued Baum. "Because development of the new formulation was already in process for integration into the Phase 2 trial for use commercially, the change has already been discussed with the FDA and is moving forward."

Glesatinib Phase 2 Trial

The Phase 2 trial for glesatinib continues in NSCLC patients with MET genetic alterations of interest who were previously treated with platinum-based chemotherapy and those who may also have had prior treatment with a checkpoint inhibitor. Enrollment is ongoing and the new formulation is being introduced this month. Patients who started on the original formulation will be transitioned to the new formulation. An interim update on response rates in patients from the Phase 2 study on the new formulation will be provided once a meaningful number of patients have been treated and are evaluable.

Patient screening continues to increase and 55 clinical sites are active globally, with approximately 130 sites planned in total. In addition to clinical screening at study sites, unique patient finding and outreach collaborations with Foundation Medicine and Guardant Health have identified more than 160 additional patients with MET amplification and exon14 deletion in the first three months. Our experience confirms the prevalence of these patient populations and the value of these collaborations, which expand our clinical reach beyond our dedicated trial sites.

The Company is exploring development of glesatinib for patients with AXL genetic alterations based upon the NSCLC AXL amplification patient who has now had a durable confirmed response to glesatinib for over a year and continues on trial.

Sitravatinib Program Update

Initial data from the Phase 1b trial of sitravatinib show early signs of clinical activity, including a confirmed PR in a Renal Cell Carcinoma (RCC) patient, as well as durable tumor regressions in multiple other tumor types, including NSCLC patients with RET mutations. The Phase 1b trial in sitravatinib continues to enroll patients with RET, CHR4q12, CBL, TRK and DDR genetic alterations in NSCLC and other solid tumors at sites in the U.S. and Korea.

A poster entitled, "A first in human Phase 1 study of receptor tyrosine kinase (RTK) inhibitor MGCD516 in patients with advanced solid tumors" presented at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting includes this initial clinical data, which further demonstrates the safety and tolerability of sitravatinib. The poster can be found at www.mirati.com.

The Phase 1b trial includes multiple cohorts to explore the safety and efficacy of sitravatinib in genetically selected patients with NSCLC, as well as cohorts in certain solid tumors where the profile of sitravatinib may provide clinical benefit. Based upon our experience to date, sitravatinib is generally well tolerated at the recommended Phase 2 dose of 150mg, administered once daily (QD).

An additional update on this trial is expected by the end of the year, when a greater number of patients have been enrolled.

Mocetinostat Program Update

The Company has initiated a trial for the combination study of mocetinostat, an HDAC (histone deacetylase) inhibitor, with the AstraZeneca/MedImmune anti-PD-L1 checkpoint inhibitor, durvalumab, in patients with NSCLC.

This trial is exploring the potential of mocetinostat to enhance the effectiveness of checkpoint inhibitors in NSCLC. The dual effect of Class I HDACs on tumor cells, as well as on immune cells, may enhance the effect of checkpoint inhibitors in all indications where checkpoint inhibitors have demonstrated efficacy.

The Company plans to provide an update on this Phase 2 trial as progress continues, with the potential to see initial signals of activity by early 2017.

About Glesatinib (MGCD265)

Glesatinib (MGCD265) is a tyrosine kinase inhibitor that potently and selectively targets tumors in patients with driver alterations in MET (mutations and gene amplification) and Axl (rearrangements and gene amplification) that occur in approximately 8% of patients with non-small cell lung cancer (NSCLC). Genetic alterations in these targets have been implicated as drivers of tumor growth and disease progression in NSCLC and other solid tumors. Glesatinib is being evaluated in a Phase 2 trial in NSCLC patients with MET genetic alterations to confirm and extend the data that supports the clinical benefit of glesatinib in patients with driver mutations in MET. Mirati retains worldwide rights to glesatinib.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

About Sitravatinib (MGCD516)

Sitravatinib (MGCD516) is being evaluated in a Phase 1b dose expansion cohort in selected patients with specific genetic alterations that are drivers of tumor growth, with an initial focus on NSCLC and in other solid tumors where sitravatinib may confer a benefit. Sitravatinib is a tyrosine kinase inhibitor with demonstrated potent inhibition of a closely related spectrum of tyrosine kinases, including RET, CBL, CHR4q12, DDR and Trk, which are key regulators of signaling pathways that lead to cell growth, survival and tumor progression. Mirati retains worldwide rights to sitravatinib.

About Mocetinostat (MGCD103)

Mocetinostat (MGCD103) is an orally-bioavailable, spectrum-selective Class I & IV HDAC inhibitor currently being studied in a Phase 2 trial as a combination therapy with durvalumab, targeting the programmed death ligand 1 (PD-L1) pathway, which has been implicated in advanced lung cancers. In preclinical models, mocetinostat with durvalumab demonstrated significant reduction in tumor volume compared to either agent alone.

About Durvalumab

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 expression enables tumors to evade detection from the immune system through binding to PD-1 on cytotoxic T lymphocytes. Durvalumab blocks PD-L1 interaction with both PD-1 and CD80 on T cells, countering the tumour’s immune- evading tactics. Durvalumab is being developed alongside other immunotherapies to activate the patient’s immune system to attack the cancer. Durvalumab is being investigated in an extensive clinical trial programme, as monotherapy or in combination with tremelimumab, in NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood cancers. In 2015, durvalumab received Fast Track Designation for the treatment of patients with PD-L1—positive metastatic SCCHN, and in 2016, durvalumab was granted Breakthrough Designation by the U.S. Food and Drug Administration as a potential treatment for metastatic urothelial bladder cancer.