1stOncology™: Cancer Intelligence Service – Page 15442 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Five Prime Presents on Novel B7-H4 Therapeutic Antibody at the 2018 AACR Annual Meeting

On April 15, 2018 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that an oral presentation featuring FPA150, Five Prime’s first-in-class B7-H4 antibody, was given today at the 2018 AACR (Free AACR Whitepaper) Annual Meeting in Chicago (Press release, Five Prime Therapeutics, APR 15, 2018, View Source [SID1234525310]). The presentation titled "FPA150: A Recombinant, Afucosylated, Fully Human IgG1 Monoclonal Antibody for the Treatment of Malignancies that Express High Levels of B7-H4" by Charles Kaplan is available at 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!

FPA150 is a novel B7-H4 antibody that possesses both T cell immune checkpoint blockade and antibody-dependent cellular cytotoxicity (ADCC) activities. FPA150 demonstrates dose-dependent anti-tumor activity in vivo as a monotherapy and elicits complete tumor regressions in preclinical tumor models when given in combination with PD-1 blockade. Five Prime is currently studying FPA150 in a Phase 1 monotherapy trial in patients with solid tumors that overexpress B7-H4.
"Our monoclonal B7-H4 antibody, FPA150, appears to possess both T cell checkpoint blockade activity and enhanced ADCC," said Bryan Irving, Ph.D., Senior Vice President of Research, at Five Prime. "We are studying FPA150 in patients whose tumors overexpress B7-H4 and in which there is high unmet need for immuno-oncology treatments, such as in breast, ovarian and endometrial cancer. Based on the therapeutic properties of FPA150, we believe that this agent has the potential to be an effective therapeutic by improving anti-tumor immune responses in cancer patients."

B7-H4 is a member of the B7-family of T cell immune checkpoint ligands and shares significant homology with other family members, including PD-L1 and PD-L2. B7-H4 is expressed in several human tumors such as carcinomas of the bladder, breast, ovary and endometrium, and its expression tends to correlate with poor prognosis. B7-H4 is also a documented T cell immune checkpoint inhibitory ligand capable of directly suppressing T cell responses.

In Investigational New Drug (IND)-enabling pharmacokinetics (PK) and toxicity studies, FPA150 demonstrated a suitable PK profile and was generally well tolerated. A B7-H4 immunohistochemistry (IHC) assay is in development for clinical use as a companion diagnostic to help identify the patients who might benefit most from this treatment.
Five Prime is studying FPA150 in a Phase 1 monotherapy trial with a dose-escalation phase in patients with solid tumors, followed by dose expansion in pre-specified cohorts in tumor types based on B7-H4 expression levels. The initial targeted tumors are advanced or metastatic breast, ovarian, endometrial and bladder cancers.

About FPA150
FPA150 is a novel, fully human, afucosylated monoclonal antibody targeting B7-H4. B7-H4 expression is observed in multiple solid tumors, including breast, bladder, ovarian and endometrial cancers, and has been documented to correlate with poor prognosis. FPA150 is designed with a dual mechanism of action: blocking the T cell checkpoint activity of B7-H4 as well as delivering potent ADCC against tumor cells expressing B7-H4. FPA150 is currently being studied in a Phase 1 clinical trial in advanced or metastatic breast, ovarian, endometrial and bladder cancers.

Blueprint Medicines Announces Proof-of-Concept Data for Highly Selective RET Inhibitor BLU-667 from Phase 1 ARROW Clinical Trial in Patients with RET-Altered Solid Tumors

On April 15, 2018 Blueprint Medicines Corporation (NASDAQ:BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, reported proof-of-concept data from the ongoing Phase 1 ARROW clinical trial of BLU-667 in patients with RET-altered solid tumors (Press release, Blueprint Medicines, APR 15, 2018, View Source;p=RssLanding&cat=news&id=2342578 [SID1234525309]). Designed and developed by Blueprint Medicines, BLU-667 is a potent and highly selective inhibitor targeting oncogenic RET fusions and mutations, which are key drivers across multiple cancers, including subsets of patients with non-small cell lung cancer (NSCLC) and medullary thyroid cancer (MTC). The data will be presented today in a clinical trials plenary session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois.

The data from the dose escalation portion of the ARROW trial showed broad and robust clinical activity for once-daily (QD) dosing of BLU-667 across multiple tumor types and RET genotypes, including in patients whose disease had progressed on prior multi-kinase inhibitor therapy. As of the data cutoff date of April 6, 2018, the data showed radiographic tumor reductions in 84 percent of patients with RET-altered solid tumors with measurable target lesions. In patients evaluable for response, preliminary overall response rates (ORR) were 50 percent in patients with NSCLC and 40 percent in patients with MTC. As of the data cutoff date, QD dosing of BLU-667 was well-tolerated, and most adverse events (AEs) reported by investigators were Grade 1 or 2.
"The data announced today reveal the broad clinical potential of BLU-667, a potent and highly selective RET inhibitor, and further demonstrate the power and reproducibility of Blueprint Medicines’ proprietary drug discovery platform," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "We believe the safety, clinical activity and pharmacodynamic results from the dose escalation portion of the Phase 1 ARROW trial demonstrate compelling proof-of-concept for BLU-667. We are particularly encouraged by the consistency of these early BLU-667 data across multiple tumor types, RET alterations and prior lines of therapy. Based on these data, we are excited to rapidly advance the global expansion portion of the trial, which will further evaluate an optimized dose of BLU-667 across a broad patient population with a focus on durability of activity."
Data from the Ongoing Phase 1 ARROW Clinical Trial
As of the data cutoff date of April 6, 2018, 53 patients had been treated with BLU-667 in the dose escalation portion of the Phase 1 ARROW clinical trial across multiple dose levels ranging from 30 mg to 600 mg QD, including 19 patients with NSCLC, 29 patients with MTC and five patients with other solid tumors. Of these 53 patients, 27 patients (51 percent) had been previously treated with a multi-kinase inhibitor and 18 patients (34 percent) had been previously treated with an immunotherapy.
Pharmacokinetic (PK) data across all QD dose levels demonstrated rapid absorption of BLU-667 and a mean half-life greater than 12 hours, supporting a QD dosing regimen.
Preliminary Safety Data:
As of the data cutoff date, QD dosing of BLU-667 was observed to be well-tolerated. The maximum tolerated dose (MTD) for BLU-667 was determined to be 400 mg QD using a Bayesian optimal interval design. At QD dose levels up to and including the MTD, the majority of AEs reported by investigators were Grade 1 or 2. AEs reported by investigators (≥20 percent) most commonly included constipation (24 percent), increased alanine aminotransferase (ALT) (22 percent) and increased aspartate aminotransferase (20 percent). Investigators reported treatment-related Grade 3 AEs in eight patients (16 percent). Treatment-related Grade 3 AEs occurring in two or more patients included hypertension and neutropenia. There were no treatment-related Grade 4 or 5 AEs.
Across all QD dose levels up to 600 mg QD, seven patients experienced dose-limiting toxicities. Only one patient discontinued treatment with BLU-667 due to a dose-limiting toxicity (Grade 3 ALT increase). An additional 11 patients discontinued treatment, including eight patients due to progressive disease, one patient due to an AE unrelated to BLU-667 and one patient due to non-compliance. One patient passed away, and the death was deemed unrelated to BLU-667. Among all 53 enrolled patients, 41 patients (77 percent) remained on BLU-667 as of the data cutoff date. Duration of treatment ranged from 0.3 to 11.5 months.
Preliminary Clinical Activity Data:
As of the data cutoff date, 40 patients with RET-altered tumors were evaluable for response assessment, including 14 patients with NSCLC, 25 patients with MTC and one patient with papillary thyroid cancer (PTC). CT and MRI imaging was used to measure clinical activity by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Of the remaining 13 enrolled patients who were not evaluable for response assessment, two patients did not have RET-altered tumors, one patient died due to an AE unrelated to BLU-667 prior to any response assessment and 10 recently enrolled patients had not been evaluated for response by the data cutoff date.
Across all evaluable patients, the preliminary ORR was 45 percent. Responses were observed in patients previously treated with multi-kinase therapy, immunotherapy and chemotherapy.
RET-altered NSCLC
85% of NSCLC patients with measurable target lesions had radiographic tumor reductions.
Seven patients achieved a partial response (PR) (five confirmed, two pending confirmation), representing a preliminary ORR of 50 percent.
Responses were observed in patients with the most common RET alterations in NSCLC, including RET-KIF5B and RET-CCDC6 fusions.
Preliminary evidence of anti-tumor activity in the brain was observed in metastatic NSCLC.
RET-altered MTC
83% of MTC patients with measurable target lesions had radiographic tumor reductions.
One patient achieved a confirmed complete response, nine patients achieved a PR (five confirmed, four pending confirmation), representing a preliminary ORR of 40 percent.
Responses were observed in patients with the most common activating RET mutations in MTC, including the RET-M918T mutation.
Other RET-altered solid tumors
One patient with RET-altered PTC achieved a PR (pending confirmation).
Based on the favorable tolerability and encouraging clinical activity observed for BLU-667 to date, Blueprint Medicines initiated and is actively enrolling patients in the global expansion portion of the ARROW trial.
Investor Event and Webcast Information
Blueprint Medicines will host an investor event on Sunday, April 15, 2018 beginning at 7:00 p.m. CT (8:00 p.m. ET) in Chicago to review the preliminary clinical data presented at AACR (Free AACR Whitepaper) for BLU-667. Formal presentations and the live webcast will begin at 7:30 p.m. CT (8:30 p.m. ET). The event can be accessed by dialing 1-855-728-4793 (domestic) or 1-503-343-6666 (international) and providing the passcode 6080608. A live webcast will also be available under "Events & Presentations" in the Investors section of Blueprint Medicines’ website at View Source The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the event concludes and will be available for 30 days following the event.
About the Phase 1 ARROW Clinical Trial of BLU-667
ARROW is a Phase 1 clinical trial of BLU-667 designed to evaluate the safety and tolerability of BLU-667 in multiple ascending doses in adults with RET-altered NSCLC, MTC and other advanced solid tumors. The trial consists of two parts: a dose escalation portion and an expansion portion. Enrollment in the dose escalation portion is complete, and the expansion portion has been initiated and is actively enrolling patients in four defined cohorts at the MTD of 400mg QD: (1) RET-altered NSCLC patients previously treated with a tyrosine kinase inhibitor (TKI), (2) RET-altered NSCLC patients who have not previously received any TKI treatment, (3) patients with medullary thyroid cancer, and (4) patients with other RET-altered solid tumors. Trial objectives include assessing response, pharmacokinetics, pharmacodynamics and safety.
Patients and physicians interested in the ARROW trial can contact the Blueprint Medicines study team at [email protected] or 1-617-714-6707. More information about the ARROW trial is also available at www.arrowtrial.com or www.clinicaltrials.gov (Identifier: NCT03037385).
About RET-Altered NSCLC, MTC and Other Solid Tumors
RET activating fusions and mutations are a key disease driver in multiple cancers, including NSCLC and MTC. RET fusions are implicated in approximately 1-2% of patients with NSCLC, while RET mutations are implicated in approximately 60% of patients with MTC. In addition, genomic analyses published by scientists at Blueprint Medicines have identified RET fusions at low frequencies in colon and breast cancer. Currently, there are no approved therapies that selectively target RET-driven cancers, though there are several approved multi-kinase inhibitors with RET activity being evaluated in clinical trials. Thus far, clinical activity attributable to RET inhibition has been uncertain for these inhibitors, likely due to insufficient inhibition of RET and off-target toxicities.
About BLU-667
BLU-667 is an orally available, potent and highly selective inhibitor designed to target RET fusions, mutations and predicted resistance mutations. Blueprint Medicines is developing BLU-667, an investigational medicine, for the treatment of patients with RET-altered NSCLC, MTC and other solid tumors. BLU-667 was discovered by Blueprint Medicine’s research team leveraging its proprietary compound library, and Blueprint Medicines retains worldwide development and commercialization rights for BLU-667.

Roche to present data on TECENTRIQ (Atezolizumab) and data from across its cancer immunotherapy portfolio at the 2018 American Association of Cancer Research (AACR) Annual Meeting

On April 14,2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will present data from across its broad cancer immunotherapy development programme, including approved and investigational medicines, during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from 14 April to 18 April in Chicago, IL, United States (Press release, Hoffmann-La Roche, APR 14, 2018, View Source [SID1234525313]). More than 42 abstracts have been accepted, including five "late breakers" and seven oral presentations.

"Through our extensive research in the areas of tumour characterisation we are developing therapies that help the immune system to mount a deep and long lasting anti-cancer response," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "A personalised combination approach of cancer immunotherapies like TECENTRIQ with various chemotherapies, targeted medicines and other immunotherapies is central to our goal of providing transformative outcomes for people living with cancer."

Key highlights from the Roche cancer immunotherapy portfolio include an updated analysis from the Phase III IMpower150 study of TECENTRIQ and Avastin plus paclitaxel and carboplatin chemotherapy in people with advanced non-squamous non-small cell lung cancer (NSCLC). The study demonstrated significantly improved progression free survival (PFS) across all PD-L1 subgroups (ITT-WT, hazard ratio [HR]=0.61; p<0.0001%; CI: 0.51-0.72), including in people whose tumours are considered PD-L1-negative regardless of the PD-L1 IHC assay used, compared to Avastin plus paclitaxel and carboplatin chemotherapy. A clinically meaningful progression free survival (PFS) advantage was also seen in people with sensitising EGFR mutations, ALK genomic rearrangements, and in people with liver metastases. Importantly, IMpower150 recently met it’s co-primary endpoint of overall survival (OS) and showed that the combination of TECENTRIQ and Avastin plus paclitaxel and carboplatin chemotherapy helped people with advanced lung cancer live longer compared to Avastin plus carboplatin and paclitaxel as an initial treatment for people with advanced NSCLC. These data will be presented at an upcoming oncology meeting in 2018.

There is a scientific rationale for combining TECENTRIQ and abraxane which suggests that the mechanisms of action of each of the medicines may be complementary in the treatment of mTNBC, as they each target different steps in the cancer immunity cycle.

Results from this single arm cohort (N=33) of the Phase 1b study of TECENTRIQ plus nab-paclitaxel chemotherapy in people with metastatic triple negative breast cancer (mTNBC) show encouraging efficacy signals, and the safety of TECENTRIQ plus nab-paclitaxel in this combination is, so far, consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.
A trend toward higher response rates and longer PFS and OS was seen for patients treated in the 1L setting compared to later lines. The ongoing randomised Phase III trial, IMpassion130, is investigating the same regimen as the Phase 1b study, with topline data expected later in 2018.

A retrospective analysis of the biology underlying primary immune escape and responsiveness to TECENTRIQ in tumour samples of people from the phase II IMvigor210 study for people with metastatic urothelial cancer showed that response to TECENTRIQ was highly associated with tumour mutational burden (TMB) and pre-existing T cell immunity. Additionally, another signalling protein known as transforming growth factor-beta (TGF-β) appears to be a negative indicator of response to TECENTRIQ, especially in the immune-excluded tumour phenotype that is common in mUC. Integration of these three independent biological features provides a foundation for understanding outcomes for people living with mUC.
Overview of key Cancer Immunotherapy data AACR (Free AACR Whitepaper) 2018

About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

TECENTRIQ is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About the TECENTRIQ (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support combining TECENTRIQ and Avastin. The TECENTRIQ and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers, including first-line advanced NSCLC. Avastin, in addition to its established anti-angiogenic effects, may further enhance TECENTRIQ’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.
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.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with TECENTRIQ to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.
To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

Hanmi calls time on troubled Tagrisso rival olmutinib

On April 13, 2018 Hanmi Pharmaceutical reported thst it’s long and turbulent development of lung cancer drug olmutinib came to an end this week after the company abandoned the program (Press release, FierceBiotech, APR 13, 2018, View Source [SID1234573812]).

The South Korean drugmaker took the decision after struggling to recruit patients into clinical trials and concluding that the third-generation EGFR inhibitor was too far behind Tagrisso (osimertinib), AstraZeneca’s fast-growing rival, to make a commercial success of the drug, according to a Korea Biomedical Review report.

Back in 2015, the olmutinib program was riding high on the back of a promising midstage data in T790M-mutated non-small cell lung cancer (NSCLC) and a $730 million licensing deal with Boehringer Ingelheim. The German company described the drug as a possible best-in-class candidate that it was hoping to pair with Merck & Co’s immuno-oncology blockbuster Keytruda in a combination trial.

Just over a year later, Boehringer backed out of the deal after taking another look at the clinical data for the drug and the increasingly crowded EGFR inhibitor market, even though olmutinib had already picked up its first approval—as Olita—in Hanmi’s home market.

Things went from bad to worse last year when the Korean authorities rapped the company for not acting quickly enough to disclose a fatality in a patient treated with the drug who developed life-threatening skin condition Stevens-Johnson syndrome (SJS). All told, the drug was linked to three cases of SJS, two of which proved fatal.

Yet more controversy ensued after Hanmi employees were accused of insider trading relating to the termination of the Boehringer deal, and the Korean firm also lost another partner for olmutinib when Chinese licensee Zai Lab returned rights to the drug.

Meanwhile, olmutinib isn’t the only Hanmi drug to run into trouble of late. Its Eli Lilly-partnered BTK inhibitor LY3337641 failed to hit its objectives in a phase 2 trial in rheumatoid arthritis, leaving the future of the program in other indications under a cloud, while at the end of 2016 a $4.2 billion, three-drug deal with Sanofi for diabetes therapies was trimmed down to two candidates.

Other partnerships with Spectrum for Rolontis (eflapegrastim) and pan-HER drug poziotinib, Johnson & Johnson for diabetes and obesity candidate HM12525A and Roche/Genentech for RAF-targeted cancer drugs currently remain on track.

Calithera Biosciences to Present New Preclinical Data for CB-839 at AACR Annual Meeting 2018

On April 13, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that preclinical research for its glutaminase inhibitor CB-839 will be shared as poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in Chicago (Press release, Calithera Biosciences, APR 13, 2018, View Source [SID1234535242]). CB-839 is a potent, selective, orally bioavailable glutaminase inhibitor in Phase 2 trials. The company and its academic collaborators will highlight data of CB-839 in novel therapeutic combinations in preclinical models of selected cancers.

"Tumor metabolism is a novel therapeutic approach that exploits the way in which cancer cells utilize nutrients to grow and survive," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "CB-839, a novel glutaminase inhibitor, has the potential to be developed in combination with standard of care cancer therapeutics such as CDK4/6 or PARP inhibitors to improve patient outcomes."

Preclinical data will be presented by Ethan Emberley, PhD, in a poster titled, "The glutaminase inhibitor CB-839 synergizes with CDK4/6 and PARP inhibitors in preclinical models," on April 17, 2018 (Abstract #3509/6). Data will be presented demonstrating that CB-839 synergizes with the CDK4/6 inhibitor palbociclib in colorectal carcinoma, triple negative breast cancer (TNBC), and ER+ breast cancer cell lines, and enhances anti-tumor activity in both an ER+ breast cancer and a colorectal cancer (CRC) xenograft tumor model. CB-839 treatment in combination with the PARP inhibitors niraparib and talazoparib has synergistic anti-proliferative activity in TNBC, CRC, non-small cell lung carcinoma, ovarian and prostate cancer cells. In vivo, the combination of CB-839 with PARP inhibitors enhances anti-tumor activity compared to single agent treatment in a CRC tumor xenograft model. Two additional posters will be presented by academic collaborators:

Suppression of clear cell ovarian carcinoma growth by glutaminase-1 inhibitor as single agent and in combination with PARP-1 inhibitor
Abstract # LB-253/20
Presenter: T. Li, Laboratory of Othon Iliopoulos, Massachusetts General Hospital Tuesday April 17, 2018

Combination treatment with CB-839 and romidepsin induces apoptosis and suppresses cell viability in preclinical models of chondrosarcoma
Abstract #1329/7
Presenter: T.N. Sheikh, Laboratory of Gary Schwartz, Columbia University Monday, April 16, 2018

About CB-839

Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents