On June 4, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it is presenting data from across its cancer immunotherapy pipeline highlighting its multipronged combination approach to cancer immunotherapy treatment (Press release, Hoffmann-La Roche , JUN 4, 2016, View Source [SID:1234512997]). The first combination trial evaluated Tecentriq with targeted therapy Cotellic in a phase Ib study in people with mCRC who had been heavily pretreated. The study demonstrated a tolerable safety profile with an Overall Response Rate (ORR) of 17 percent (n=4). All responders had the KRAS gene mutation, and responses were observed irrespective of Microsatellite Instability (MSI) status. Responses were ongoing in two out of four people at the time of data analysis. The second evaluated a combination with Tecentriq and Abraxane chemotherapy in a phase Ib study for people with mTNBC. The results showed that the safety profile was similar to that previously seen with Tecentriq or Abraxane chemotherapy alone. An ORR of 38% (n=32) was observed across all lines of therapy. The final combination being presented are dose-escalation results from the ongoing phase Ib study of the investigational Roche cancer immunotherapy molecule (MOXR0916, anti-OX40) and Tecentriq. The data showed a favourable safety profile and evidence of immune activation, supporting the continuation of further investigation into the potential benefits this combination could bring to patients.

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"Combinations based on a deep understanding of the science are a central component of our cancer immunotherapy development strategy.’’ said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We believe we may be able to bring the full potential of treatments such as Tecentriq to a greater number of people by exploiting different mechanisms of action in combination, such as with chemotherapy, targeted treatments and other immunotherapy agents.’’

Further information on Roche’s contribution to the ASCO (Free ASCO Whitepaper) 2016 scientific programme, the company’s wider progress in cancer care and key data being presented at the conference will be featured at a Roche investor briefing on Sunday 5 June between 6pm – 8pm CDT. This event is independently organised by Roche and is open to analysts attending the ASCO (Free ASCO Whitepaper) 2016 Annual Meeting. To register for the Roche investor briefing, please use the following link:
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To learn more about Roche’s personalised cancer immunotherapy programme and Roche’s contribution to ASCO (Free ASCO Whitepaper) 2016, please follow Roche on Twitter via @Roche. You can keep up to date with ASCO (Free ASCO Whitepaper) 2016 Annual Meeting news and updates by using the hashtag #ASCO16.

About the phase Ib combination study of Tecentriq with Cotellic in advanced CRC
Overview and study design
A phase Ib, open-label, multicentre study designed to assess the safety, tolerability and pharmacokinetics of co-administration of intravenous dosing of Tecentriq and oral dosing of Cotellic in participants with metastatic or locally advanced cancer for which standard therapies have been exhausted

The primary endpoints of the study were safety and tolerability with secondary endpoints including ORR confirmed by RECIST v1.1

23 CRC (22 KRAS mutant, one wild type) patients were enrolled during escalation and expansion

Cobimetinib was escalated from 20 mg to 60 mg daily (21 days on/7 days off) and combined with Tecentriq 800 mg IV q2w

About the phase Ib combination study of Tecentriq with Abraxne in mTNBC
Overview and study design

GP28328 (NCT01633970) was a multi-centre, multi-arm study evaluating Tecentriq in combination with Abraxane chemotherapy. Arm F consisted of patients with TNBC (up to 3 prior lines of chemotherapy were allowed)

— The primary endpoint was safety and tolerability

— Secondary endpoints included efficacy per RECIST v1.1 criteria (best overall response, objective response rate, duration of response, progression-free survival) and immune-related response criteria (irRC), pharmacokinetics and biomarker analyses

About the phase Ib study of MOXR0916 (OX40) and Tecentriq in advanced solid tumours
Overview and study design

A phase Ib, open-label, multicentre study evaluating the safety and pharmacokinetics of MOXR0916 and Tecentriq in patients with locally advanced or metastatic solid tumours

The primary endpoint of the study is safety and tolerability,

A 3+3 dose-escalation was conducted with a 21-day window to evaluate dose-limiting toxicity

— Escalating doses of MOXR0916 in combination with a fixed 1200 mg dose of Tecentriq were administered every three weeks (q3w)

An expansion cohort to enable immune profiling of serial tumour biopsies was also enrolled

28 patients were treated in eight dose-escalation cohorts (MOXR0916 dose levels 0.8–1200 mg) and 23 additional patients were treated in the serial biopsy cohort

— The median number of prior therapies for metastatic disease was two (range 0–7) and nine patients had received prior PD-1/PD-L1 antibodies

Results:
No dose-limiting toxicities, Grade 4/5 adverse events (AEs) attributed to study treatment or related AEs leading to treatment discontinuation were reported

— The majority of treatment-related AEs were Grade 1 in severity; one related Grade 3 event (pneumonitis responsive to corticosteroids) was reported

Evidence of immune activation, including upregulation of PD-L1, was observed in paired tumour biopsies from some patients, including patients whose immediate prior therapy was anti-PD-1

The regimen selected for dose expansion is MOXR0916 300 mg + Tecentriq 1200 mg q3w. Evaluation of efficacy is ongoing in expansion cohorts for patients with melanoma, RCC, NSCLC, urothelial carcinoma, and TNBC.

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.

About personalised cancer immunotherapy
The aim of personalised cancer immunotherapy (PCI) is to provide individual patients with treatment options that are tailored to their specific needs. The Roche PCI research and development programme comprises more than 20 investigational candidates, nine of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for Roche medicines. In the case of Tecentriq, PCI begins with the PD-L1 (programmed death ligand-1) IHC assay based on the SP142 antibody developed by Roche Tissue Diagnostics. The goal of PD-L1 as a biomarker is to identify those people most likely to experience clinical benefit with Tecentriq as a single agent versus those who may benefit more from combination approaches; the purpose is to inform treatment strategies which will give the greatest number of patients a chance for transformative benefit. The ability to combine TECENTRIQ with multiple chemotherapies may provide new treatment options to people across a broad range of tumours regardless of their level of PD-L1 expression.

PCI is an essential component of how Roche delivers on the broader commitment to personalised healthcare.

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to directly bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq may also affect normal cells.

About MOXR0916 (anti-OX40)
MOXR0916 is an agonist monoclonal antibody that targets OX40, a costimulatory receptor that is expressed by T cells, and results in activation rather than blockade of the OX40 signaling pathway. MOXR0916 is thought to promote anti-tumour immunity by binding to OX40 on both antigen-experienced effector T cells, thereby enhancing their proliferation and survival, and on activated regulatory T cells, thereby inhibiting their suppressive function. Because Tecentriq and MOXR0916 act through distinct but complementary mechanisms, in combination these investigational immunotherapies have the potential to enhance activation of CD8+ T-cells that mediate anti-tumour immune responses.

On June 04, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported the oral presentation of positive clinical data from its ongoing SL-401 Phase 2 potentially pivotal clinical trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Stemline Therapeutics, JUN 4, 2016, View Source [SID:1234513081]). The Phase 2 trial results were delivered today by Naveen Pemmaraju, M.D. from the University of Texas MD Anderson Cancer Center, via an oral presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, IL.

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The data presented at ASCO (Free ASCO Whitepaper) cover 24 BPDCN patients treated with SL-401 (19 evaluable for response, 4 recently treated/efficacy assessment pending, and 1 non-evaluable patient). Results demonstrate that SL-401 produced an 89% (17/19) overall response rate (ORR) in BPDCN, with a 100% (12/12) ORR in first-line patients and a 71% (5/7) ORR in relapsed/refractory patients, including one compassionate use patient (see Table 1). In 12 evaluable first-line patients (all doses), there were 9 complete responses (CR) and 2 clinical complete responses (CRc). CRc is defined as a CR in non-skin affected organs with marked gross clearance of skin lesions and residual microscopic skin disease. In the 10 evaluable first-line patients treated at 12 ug/kg/day, the CR/CRc rate was 100% (8 CR and 2 CRc). In the 7 evaluable relapsed/refractory BPDCN patients, including one treated on a compassionate use basis, the ORR rate was 71%, which included 1 CR and 1 CRc (29% CR/CRc rate) and 3 partial responses (PR).

Response duration data continue to mature and appear promising. 75% (9/12) first-line BPDCN patients treated at 12 ug/kg/day remained relapse-free (1+-13+ months). This includes five patients receiving ongoing SL-401 therapy (1+-9+ months; 1+-12+ cycles), and four patients who were successfully bridged to stem cell transplant (SCT) and remain in remission (6+-13+ months after the first dose of SL-401 and 1+-7+ months post-SCT). In the relapse/refractory setting, 43% (3/7) of patients were progression-free and receiving ongoing SL-401 (0.5+-3+ months). Patients are being followed for progression free survival (PFS) and overall survival (OS) which, while early, are both trending favorably.

The most common side effects were transaminitis and hypoalbuminemia (see Table 2), which were both largely transient and not dose limiting. Dosing and safety parameters were developed during the lead-in stage of the study to minimize the risk of severe capillary leak syndrome. Since implementation of these measures, SL-401 at doses of 12 ug/kg/day has demonstrated a manageable safety and tolerability profile. Also, multiple consecutive cycles of SL-401 at 12 ug/kg/day were not associated with cumulative side effects.

Naveen Pemmaraju, M.D., Assistant Professor, Department of Leukemia at the University of Texas MD Anderson Cancer Center (Houston, TX), an investigator on the study, commented, "SL-401’s remarkable results to date suggest the agent could very well emerge as the standard of care for both first-line and relapsed/refractory BPDCN, a devastating disease for which there had previously been no effective therapy. Overall, we continue to see very strong activity with SL-401 in both first line and relapsed/refractory patients, and the safety profile continues to be manageable over increasing patient experience. Notably, we have also been able to successfully bridge several patients to transplant which, for the most part, has not been possible at this frequency with existing therapies." Dr. Pemmaraju continued, "We look forward to working closely with Stemline to bring this promising new agent to patients as quickly as possible in BPDCN and other malignancies."

Andrew A. Lane, M.D., Ph.D., Assistant Professor, Medical Oncology at the Dana-Farber Cancer Institute (Boston, MA), and a co-author on the study, commented, "The SL-401 clinical data in first-line and relapsed/refractory BPDCN continues to demonstrate exciting outcomes in these two underserved patient populations, and represents a promising new option for patients with this devastating disease." Dr. Lane continued, "We are very pleased to be ongoing contributors to this study, and look forward to helping to advance this active agent in both BPDCN and other hematologic malignancies as well."

Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "We are excited by SL-401’s continued robust clinical data in all lines of BPDCN. SL-401 appears to be a potent agent, demonstrating a rapid onset of action and promising response durability, while its tolerability profile makes it well-suited for either long-term use or bridging BPDCN patients to transplant." Dr. Bergstein concluded, "Over the remainder of the year, we will continue to enroll first-line and relapsed/refractory patients in this ongoing trial, ramp up our disease awareness efforts, and advance our ongoing regulatory interactions in order to bring this agent to market as soon as possible in both settings."

The tables below summarize efficacy and safety observed in the Phase 2 potentially pivotal trial in BPDCN. Enrollment is ongoing and additional data will be available throughout 2016.

Table 1. Overview of SL-401 Clinical Activity in BPDCN

Major objective responses

89% (17/19) ORR in BPDCN (all lines/all doses)
4 additional recently-treated patients (2 first-line and 2 R/R) not yet evaluable for response
100% (12/12) ORR in first-line BPDCN (all doses)
100% (10/10) CR/CRc rate in first-line BPDCN (12 ug/kg/day)
71% (5/7) ORR in R/R BPDCN
29% (2/7) CR/CRc rate in R/R BPDCN
Response duration data maturing

75% (9/12) first-line BPDCN patients treated at 12 ug/kg/day were progression-free (1+-13+ months). This includes:
5 patients receiving ongoing SL-401 therapy (1+-9+ months; 1+-12+ cycles); and
4 patients who were successfully bridged to stem cell transplant (SCT) and remain in remission (6+-13+ months post-first SL-401 dose; 1+-7+ months post-SCT).
43% (3/7) of R/R BPDCN patients were progression-free and receiving ongoing SL-401 (0.5+-3+ months)
Patients continue to be followed for progression free survival (PFS) and overall survival (OS) and, while early, both are trending favorably

Line of Therapy All lines First-line First-line R/R1
Dose Group All Doses All Doses 12 ug/kg 12 ug/kg
n (total) 242 15 12 9
n (evaluable) 19 12 10 7
ORR 89 % 100 % 100 % 71 %
CR/CRc, n (rate) 13 (68%) 11 (92%) 10 (100%) 2 (29%)
PR 4 1 - 3
n, stem cell transplant
(SCT; auto-SCT n=3; allo-SCT n=1) 4 4 4 -
1Includes one patient treated on a compassionate use basis
2Includes 4 patients were recently treated with SL-401 and response assessment is pending

Source: ASCO (Free ASCO Whitepaper), 2016

Table 2. Overview of SL-401 Safety in BPDCN

Most Common Adverse Events (≥ 15% treatment-related adverse effects, TRAEs)
All Grades (%) Grade ≥ 3 (%)
TRAEs All AEs TRAEs All AEs
Transaminase elevation 61 74 57 61
Hypoalbuminemia 43 48 0 0
Chills 35 39 0 0
Pyrexia 30 48 0 0
Nausea 26 52 0 0
Fatigue 26 43 0 9
Thrombocytopenia 22 22 22 22
Hypotension 22 22 0 0
Weight increased 22 30 0 0
Capillary leak syndrome 22 22 9 9
Anemia 17 30 13 17
Decreased appetite 17 22 0 0
Edema peripheral 17 43 0 0

On June 04, 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 1b trial of FP-1039/GSK3052230 (hereafter FP-1039) in mesothelioma patients were reported today in a poster presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Five Prime Therapeutics, JUN 4, 2016, View Source [SID:1234512998]). Dr. Jose Trigo from the Hospital Universitario Virgen de la Victoria, Málaga, Spain, presented the poster, titled Multi-arm, open-label Phase 1b study of FP-1039/GSK3052230 with chemotherapy in malignant pleural mesothelioma (MPM). The poster is available on the Five Prime website: View Source

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The mesothelioma arm of the open-label Phase 1b trial evaluated weekly infusions of FP-1039, an FGF ligand trap, in combination with 1st-line pemetrexed and cisplatin in patients with untreated, unresectable MPM. Following the dose escalation portion of the trial, 15 mg/kg of FP-1039 was identified as the maximum tolerated dose (MTD) and established as the dose for expansion in patients with MPM. The primary study endpoints are safety and response rates, with Progression Free Survival (PFS), duration of response and translational measures as secondary endpoints. The poster includes data from 34 MPM patients who had received doses of FP-1039 as of the April 18, 2016 data cut-off and 18 patients were continuing on the trial at that time point.

Safety Data

The most common adverse events (AEs; all grades) observed were: nausea (53%), decreased appetite (41%) and fatigue (35%)
The vast majority of events were Grades 1-2
Three dose-limiting toxicities (DLTs) were reported at the 20 mg/kg dose (Grade 5 bowel perforation/ischemia, Grade 3 elevated creatinine level and Grade 3 infusion reaction) whereas no DLTs were reported at 15 mg/kg, and thus maximum tolerated dose (MTD) was established at 15 mg/kg
Toxicities associated with small-molecule FGFR inhibitors, such as hyperphosphatemia, retinal detachment and nailbed changes, have not been observed.
Efficacy Data
In the 18 patients evaluable as of April 18, 2016 who had received FP-1039 doses at or below the 15 mg/kg MTD:

Preliminary Objective Response Rate (ORR) was 39%, with a Disease Control Rate (DCR) of 100%, evaluated per mRECIST 1.1
7 confirmed Partial Responses (PRs) and 11 Stable Disease (SD)
Evaluable patients are defined as patients who enrolled at least 42 days (2 cycles) prior to the cutoff date, which was also the minimum time duration utilized in the calculation of DCR
Median Progression Free Survival (PFS) was 6.8 months, though the data are still maturing.
More than 50% (19 out of 34 dosed) of mesothelioma patients are still on trial
"The data continue to evolve and we are hopeful that FP-1039 will be shown to have potential benefit for patients with mesothelioma. Several mesothelioma patients were still on study at the time of the data cut off, so we will continue to follow their progress," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "We are currently working with GSK to complete the trial and will be monitoring the quality and durability of patient responses and evaluating drug supply, manufacturing and other considerations as we determine the future plans for FP-1039."

About FP-1039
FP-1039 is a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to FGF ligands circulating in the extracellular space (such as FGF2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells. Treatment with FP-1039 treatment has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF-23. GlaxoSmithKline (GSK) is completing the ongoing Phase 1b trial in malignant pleural mesothelioma and will transfer its development and commercialization rights for FP-1039 back to Five Prime upon completion.

On June 04, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported an update on its clinical development pipeline during an investor briefing and webcast held in conjunction with the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 annual meeting (Press release, TESARO, JUN 4, 2016, View Source [SID:1234513083]).

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During the investor briefing, TESARO announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for an intravenous (IV) formulation of rolapitant. The FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of January 11, 2017. The NDA for rolapitant IV is supported by data from a clinical program of approximately 350 subjects, and included a bioequivalence study and several other supportive non-clinical and clinical studies.

TESARO also provided an update on its Phase 3 NOVA trial of niraparib in patients with ovarian cancer. A sufficient number of progression free survival (PFS) events has been reached to trigger data analysis for both cohorts. Data cleaning is underway in preparation for database lock and release of top-line results. Finally, TESARO announced FDA clearance of its Investigational New Drug (IND) application for TSR-022, its anti-TIM-3 antibody candidate. A Phase 1 study for TSR-022 is planned to begin in mid-2016.

"We continue to make significant progress with our pipeline of oncology product candidates. The acceptance of the rolapitant IV NDA and clearance of TSR-022 IND are important milestones for TESARO and demonstrate our commitment to advancing new therapeutic options for patients," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Our NOVA study results will be the first data from a prospectively designed, randomized, Phase 3 trial of a PARP inhibitor, and we look forward to sharing these data later this quarter."

About Intravenous Rolapitant
Rolapitant IV is a potent and selective NK-1 receptor antagonist with an extended plasma half-life that is being developed for the prevention of chemotherapy-induced nausea and vomiting (CINV). NK-1 receptors are highly concentrated in the brain and bind the neurokinin substance P. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by emetogenic stimuli, including certain cancer chemotherapies. NK-1 receptor antagonists have been demonstrated to improve the management of nausea and vomiting experienced by cancer patients undergoing emetogenic chemotherapy. TESARO licensed exclusive rights for the development, manufacture, commercialization, and distribution of rolapitant from OPKO Health, Inc.

About Niraparib
Niraparib is a potent, oral PARP inhibitor that is currently being evaluated in four ongoing pivotal trials. TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing monotherapy development program for niraparib includes a Phase 3 trial in patients with ovarian cancer (the NOVA trial), a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial), a Phase 3 trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial), and a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial). Several combination studies are also underway, including trials of niraparib plus pembrolizumab, bevacizumab, and temozolomide.

About TSR-022

TSR-022 is a monoclonal antibody candidate targeting TIM-3 and was developed as part of a collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drug candidates targeting PD-1 (TSR-042), TIM-3 (TSR-022), and LAG-3 (TSR-033), and bi-specific antibody drug candidates targeting PD-1/TIM-3 and PD-1/LAG-3, in addition to a novel bi-specific antibody candidate designed to target undisclosed targets.

On June 4, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported new critical genomics data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 demonstrating the clinical significance of comprehensive genomic profiling (CGP) with FoundationOne in identifying patients with advanced lung cancer most likely to respond to RET inhibitor targeted therapies and also to predict those patients likely to develop resistance to targeted therapy (Press release, Foundation Medicine, JUN 4, 2016, View Source [SID:1234513018]).

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Key Data Highlights:

The poster titled, "MDM2 amplification (Amp) to mediate cabozantinib resistance in patients (Pts) with advanced RET-rearranged lung cancers," presented by Romel Somwar, Ph.D., senior research scientist, pathology, Memorial Sloan Kettering Cancer Center, analyzes the genomic profiles of patients treated with the RET inhibitor, cabozantinib, to better understand the molecular mechanisms that underlie intrinsic and secondary resistance. Key study findings include:

Comprehensive genomic profiles were performed on 3,842 lung cancer patients, detecting concurrent MDM2 amplification in 20 percent of tumors with RET fusions
In RET-rearranged cell lines and xenografts treated with cabozantinib and the MDM2 inhibitors, AMG232 and RG7388, a combination of cabozantinib and AMG232 proved more effective at suppressing tumor growth than either agent alone
The study shows that MDM2 amplification is a potential mechanism of primary or acquired resistance to cabozantinib, and therefore MDM2 inhibitors might be studied clinically to prevent the development of acquired resistance and enable longer, more durable responses to treatment
The second poster presentation titled, "Significant systemic and CNS activity of RET inhibitor vandetanib combined with mTOR inhibitor everolimus in patients with advanced NSCLC with RET fusion," by Tina Cascone, M.D., Ph.D. and Vivek Subbiah, M.D., from The University of Texas MD Anderson Cancer Center, demonstrates that targeted combination therapy of vandetanib with the mTOR inhibitor, everolimus, was tolerable and demonstrated significant activity in RET rearranged NSCLC. Key study findings include:

Vandetanib and everolimus were administered to 13 stage IV NSCLC patients, including six patients with tumors harboring RET fusions
All six patients with RET fusions experienced a response, including five partial responses and one patient with stable disease
The six patients with RET fusions were identified using CGP with FoundationOne. Notably, two additional patients tested positive for RET fusions using FISH and did not respond to treatment.
The study suggests that combination therapy was superior to monotherapy with RET inhibitors, warranting further studies of this combination. The study further highlights the superior accuracy of CGP for calling fusions over traditional single gene tests, like FISH.
"By helping us better understand the likelihood of response and resistance to certain therapies, CGP is providing information that can help improve physician treatment decisions and ultimately, we believe, lead to better patient outcomes," said Vincent Miller, M.D., chief medical officer, Foundation Medicine. "Additionally, the sensitivity and accuracy of FoundationOne to reliably detect all classes of clinically relevant alterations in non-small cell lung cancer allow us to circumvent the false positives that often arise with single gene and standard hotspot testing. As this study shows, inaccuracies in genomic testing can lead to unnecessary and often unsuccessful treatments, as well as inefficient and costly care delivery."

Genomic alterations in the RET gene are found in several different types of cancer. RET gene fusions occur in 1 percent of non-small cell lung cancers (NSCLC) and are well-established oncogenic drivers. The RET inhibitor agents, vandetanib and cabozantinib, have demonstrated antitumor activity in NSCLC patients harboring RET fusions, although data suggest that objective responses are observed in only a minority of patients, and progression-free survival (PFS) is shorter than with other oncogene targeted therapies in this disease. A portion of tumors may harbor intrinsic resistance to RET inhibitors, while some respond but eventually progress, yielding to the development of secondary resistance. However, molecular mechanisms that underlie resistance to cabozantinib are poorly understood. Taken together, these studies reinforce the critical importance of FoundationOne in identifying patients likely to respond to targeted therapies and to predict those patients likely to develop resistance.

Lung cancer is by far the leading cause of death among both men and women; about 1 out of 4 cancer deaths are from lung cancer1. There are two major types of lung cancer: NSCLC and small cell lung cancer (SCLC). NSCLC is the most common and accounts for approximately 85 percent of all lung cancer cases2. The American Cancer Society estimates there will be about 224,390 new cases of lung cancer in the United States for 2016 and about 158,080 deaths1.