On May 29, 2020 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported updated data from the ongoing Phase 1 study evaluating single agent vorasidenib in isocitrate dehydrogenase (IDH)-mutant advanced solid tumors, including glioma (Press release, Agios Pharmaceuticals, MAY 29, 2020, View Source [SID1234558671]). Data from the non-enhancing glioma population were featured in an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, which is being held virtually. Vorasidenib, an investigational, oral, selective, brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent Grade 2 non-enhancing glioma.

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"For patients with IDH-mutant non-enhancing glioma who currently have limited treatment options beyond chemotherapy and radiation, targeted oral options such as vorasidenib are urgently needed," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the Phase 1 dose-escalation study. "The updated results of this study in non-enhancing glioma patients provide further evidence of the potential benefit of vorasidenib for these patients, with a favorable safety profile and encouraging preliminary activity, including prolonged disease control, objective tumor responses, and clinically meaningful progression-free survival rates."

"These promising efficacy and safety data in patients with IDH-mutant non-enhancing glioma provide further support for our registration-enabling Phase 3 INDIGO study," said Chris Bowden, M.D., chief medical officer at Agios. "With vorasidenib – the first and only brain-penetrant IDH inhibitor in Phase 3 trials for low-grade glioma – we have an opportunity to target a highly prevalent driver mutation early in the disease evolution, providing a therapeutic alternative to ‘watch and wait’ that can potentially delay the need for chemotherapy and radiation."

Vorasidenib Phase 1 Dose-Escalation Study

Vorasidenib is being evaluated as a single agent in an ongoing Phase 1 dose-escalation trial in IDH1/2 mutant advanced solid tumors (n=93), including glioma (n=52). Enrollment was completed in June 2017. As of the March 3, 2020 data cut-off, study design, enrollment and baseline characteristics of the 22 non-enhancing glioma patients are reported below:

Seventy-seven percent of patients (n=17) had World Health Organization (WHO) classified Grade 2 tumors and 23% (n=5) had Grade 3 tumors.
Ninety-one percent of patients (n=20) had an IDH1 mutation and 5% (n=1) had an IDH2 mutation. One patient did not have a biopsy but was confirmed as IDH mutant positive due to 2-HG elevation by magnetic resonance spectroscopy (MRS).
The median age of these patients is 47 years (ranging from 16 to 73).
Sixty-four percent of patients (n=14) had received prior systemic therapy. Patients had received a median of two prior systemic therapies (ranging from 1 to 4).
Fifty-nine percent of patients (n=13) had previously received temozolomide and 36% (n=8) of patients received prior radiation therapy.
Patients received daily doses of vorasidenib ranging from 10 mg to 200 mg.
Thirty-six percent of patients (n=8) remain on treatment.
Safety Data

The safety analysis conducted on the 22 patients with non-enhancing glioma as of the data cut-off demonstrated that vorasidenib has a favorable safety profile at dose levels below 100 mg once daily. Safety data for this population are consistent with the results reported for all patients enrolled in this trial at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting.

The majority of adverse events (AEs) reported by investigators were mild to moderate, with the most common (>40%) across all grades being increased alanine aminotransferase (ALT) (64%), increased aspartate aminotransferase (AST) (59%), nausea (46%) and headache (41%).
Grade 3 or higher AEs were observed in 27% of patients (n=6) with the most common being increased ALT (9%) and AST (9%).
AEs of Grade 2 or higher elevated transaminases occurred in seven non-enhancing glioma patients at the higher dose levels (≥100 mg) and resolved to Grade ≤1 with dose modification or discontinuation.
No AEs of Grade 2 or higher elevated transaminases were observed in patients at the lower dose levels (<100 mg).
Of the 14 (64%) patients who discontinued treatment, 9% (n=2) discontinued due to an AE.
Efficacy Data

Efficacy data from the 22 non-enhancing glioma patients as of the data cut-off showed:

The investigator-reported objective response rate (ORR) was 18% with one patient exhibiting a partial response and three patients exhibiting minor responses using the Response Assessment in Neuro-Oncology for low-grade glioma (RANO-LGG) criteria.
Seventy-three percent of patients (n=16) achieved stable disease according to the investigator as assessed by RANO-LGG.
With 59% of events reported, median progression free survival (PFS) was 31.4 months (95% CI 11.2, 40.8).
Twenty-four month PFS rate was 55.4%.
The median treatment duration was 25.8 months (ranging from 1.0 to 47.9) with 68% (n=15) remaining on treatment for ≥1 year.
Ongoing Phase 3 INDIGO Trials in Progress Poster
A trials in progress poster was presented at the 2020 ASCO (Free ASCO Whitepaper) Annual Meeting to highlight the ongoing global, randomized, placebo-controlled Phase 3 INDIGO study of vorasidenib in approximately 366 patients with residual or recurrent, non-enhancing, Grade 2 low-grade glioma with an IDH1 or IDH2 mutation and who have undergone surgery as their only treatment. The goal of the study is to evaluate the efficacy of vorasidenib compared with placebo based on radiographic PFS and determine whether vorasidenib could provide a therapeutic alternative to "watch and wait" to help control low-grade glioma and potentially delay the need for chemotherapy and/or radiation. The study is currently enrolling. More information can be found on the INDIGO study website.

Vorasidenib is not approved in any country for the treatment of patients with low-grade glioma.

About Glioma
Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low-grade glioma) to rapidly progressing (high-grade glioma-Glioblastoma Multiforme). Tumor enhancement is an imaging characteristic assessed by magnetic resonance imaging (MRI), and enhancing tumors are more likely to be high-grade.

Common symptoms of glioma include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor, and regardless of treatment, the majority of patients with low-grade gliomas will have recurrent disease that will progress over time. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80 percent have an IDH mutation.

On May 29, 2020 eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulation inhibitors (STRIs) for the treatment of cancer, reported that positive Phase 2 data from its pipeline program tomivosertib (eFT508), will be presented at the ASCO (Free ASCO Whitepaper) 2020 Virtual Scientific Program at 8:00 a.m. ET on May 29 (Press release, eFFECTOR Therapeutics, MAY 29, 2020, View Source [SID1234558687]). The data demonstrates tomivosertib’s potential as a therapeutic solution for common resistance mechanisms to checkpoint inhibitors.

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In a Phase 2 study, open-label study, tomivosertib demonstrated antitumor activity in combination with check point inhibitors (CPI) in patients with solid tumors who progressed on CPI treatment. In the study, 41% of patients with non-small cell lung cancer treated with tomivosertib showed progression free survival at 24 weeks. The median progression free survival rate was 19 weeks, and all NSCLC subjects entered the study with progression by RECIST 1.1 on single agent checkpoint inhibitor prior to adding tomivosertib.

"Tomivosertib was designed to down regulate multiple immunosuppressive factors by acting at the level of mRNA translation and our clinical data continue to highlight the potential of tomivosertib to complement focused immune checkpoint inhibitor activity such as anti-PD-1 and PD-L1 agents," said Steve Worland, Ph.D., president and chief executive officer of eFFECTOR. "This study underscores the importance of progression free survival for patients who may experience extended and improved quality of life on checkpoint inhibitors with the addition of tomivosertib prior to switching to cytotoxic salvage therapy."

Secondary objectives for the current study include characterizing the pharmacokinetics and safety of tomivosertib when added to an anti-PD-1/anti PD-L1 therapy. There were no grade 5 treatment-emergent adverse events (TEAEs) related to tomivosertib and the majority of TEAEs were grade 1 or 2.

About Tomivosertib (eFT508)
Tomivosertib is eFFECTOR’s wholly-owned, highly selective translation regulation inhibitor that targets MNK1 and MNK2 (MNK1/2) acting at the level of mRNA translation. The oral small molecule drug candidate promotes anti-tumor immune activity by selective down regulation of several immune checkpoint receptors and specific immunosuppressive cytokines. Tomivosertib is being evaluated as an add-on when patients are experiencing insufficient response to an FDA-approved checkpoint inhibitor [NCT03616834].It is also under evaluation in advanced breast cancer in combination with paclitaxel as part of a study led by researchers at McGill University and fully funded by Stand Up to Cancer Canada.

On May 29, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported data from the ongoing ARROW clinical trial of pralsetinib in patients with RET fusion-positive non-small cell lung cancer (NSCLC), thyroid cancer and other solid tumors (Press release, Blueprint Medicines, MAY 29, 2020, View Source [SID1234558705]). Registrational data for pralsetinib in patients with RET fusion-positive NSCLC showed deep and durable clinical responses, with a median duration of response (DOR) not reached. Additional results showed the broad clinical activity of pralsetinib across other RET fusion-positive tumors, including thyroid cancer. Pralsetinib was well-tolerated and safety results were consistent with prior data, with no new safety signals observed. These results are being presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 (ASCO20) Virtual Scientific Program.

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In addition, Blueprint Medicines reported that the U.S. and EU marketing applications for pralsetinib for the treatment of locally advanced or metastatic RET fusion-positive NSCLC have been accepted by the U.S. Food and Drug Administration (FDA) and validated by the European Medicines Agency (EMA), respectively. The FDA granted priority review and set an action date of November 23, 2020 under the Prescription Drug User Fee Act. Blueprint Medicines plans to submit an NDA for pralsetinib for advanced RET mutant and RET fusion-positive thyroid cancers in June 2020, under the FDA’sOncology Center of Excellence Real-Time Oncology Review pilot program.

"The use of targeted therapies for molecularly defined subsets of patients is fundamentally altering the treatment of non-small cell lung cancer and, similar to oncogenes like EGFR and ALK, RET is a proven driver and promising therapeutic target," said Justin Gainor, M.D., Director of the Center for Thoracic Cancers and Targeted Immunotherapy at Massachusetts General Hospital Cancer Center and an investigator on the ARROW trial. "The ARROW trial results presented today during the ASCO (Free ASCO Whitepaper) virtual meeting showed that patients with RET fusion-positive lung cancer treated with the selective RET inhibitor pralsetinib had durable responses. In addition to supporting the development of pralsetinib across a broad population, these data highlight the urgency to test lung cancer patients with next-generation sequencing so that eligible patients may be identified for treatment."

"Building on a unique preclinical profile characterized by selectivity for RET and equipotent activity against predicted resistance mutations, the clinical data for pralsetinib is showing high complete response rates, prolonged durability and a favorable safety profile as a convenient once-daily oral treatment. With this differentiated profile, pralsetinib has the potential to change the standard of care for patients with RET-altered non-small cell lung cancer and thyroid cancer," said Andy Boral, M.D., Ph.D., Chief Medical Officer of Blueprint Medicines. "More broadly, data presented during the ASCO (Free ASCO Whitepaper) virtual meeting highlight the clinical activity of pralsetinib across ten distinct RET-altered tumor types. These results strongly support continued development of pralsetinib across all RET-altered cancers, regardless of a tumor’s tissue of origin, with the goal of delivering transformative benefit to the broadest possible patient population."

Clinical Activity Data

The reported data included response-evaluable populations comprising 116 patients with NSCLC who received a starting dose of 400 mg once daily (QD), including 80 patients with NSCLC previously treated with platinum-based chemotherapy and 26 patients with treatment-naïve NSCLC, 11 patients with RET fusion-positive thyroid cancer, and 12 patients with other RET fusion-positive cancers. Tumor response was assessed by blinded, independent central review using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

RET Fusion-Positive NSCLC

As of a data cutoff of November 18, 2019, pralsetinib demonstrated consistent and robust clinical activity in RET fusion-positive NSCLC, regardless of prior therapy, RET fusion partner or central nervous system (CNS) involvement.

In 80 patients who previously received platinum-based chemotherapy, the ORR was 61 percent (95% CI: 50-72%). Two partial responses (PR) were pending confirmation at the time of the data cut off and were subsequently confirmed. Five percent of patients had a confirmed response (CR) and 14 percent of patients had complete regression of target tumors.

In 26 patients with no prior systemic therapy, the confirmed ORR was 73 percent (95% CI: 52-88%), and the CR rate was 12 percent.

Across all 116 patients, regardless of prior therapy, the median DOR was not reached (95% CI: 11 months, not reached), and the 6-month DOR was 86 percent. Overall, 74 percent of confirmed responders, including all patients with CRs, were on treatment as of the data cutoff.

Robust and durable intracranial activity was shown in nine patients with measurable CNS metastases at baseline. All patients had shrinkage of CNS metastases, with an intracranial CR rate of 33 percent. No CNS responders experienced CNS progressive events. The median CNS DOR was not reached, with ongoing treatment durations up to 12 months in patients with measurable CNS metastases. Among patients without a history of CNS metastases, none have developed new CNS metastases on study as of the data cutoff date.

Other RET Fusion-Positive Cancers

As of a data cutoff of February 13, 2020, pralsetinib demonstrated robust clinical activity in a range of additional RET fusion-positive cancers. In 11 patients with RET fusion-positive thyroid cancer (10 previously treated with systemic therapy), the centrally confirmed ORR was 91 percent (95% CI: 59-100%), and the disease control rate was 100 percent (95% CI: 72-100%). Overall, 70 percent of responders remain on therapy with ongoing treatment durations up to 22 months as of the data cutoff. Across 12 patients with other RET fusion-positive cancers previously treated with systemic therapy, the investigator-assessed ORR was 50 percent (95% CI: 21‒79), with one PR pending confirmation. Responses were observed in all evaluable patients with pancreatic adenocarcinoma (n=3) and cholangiocarcinoma (n=2), tumor types with a typically poor prognosis.

Safety Data

As previously reported, as of the data cutoff date of November 18, 2019, a total of 354 patients were enrolled in the ARROW trial at a starting dose of 400 mg QD. Overall, safety results were consistent with previously reported data. Pralsetinib was well-tolerated across tumor types, and most treatment-related adverse events (AEs) were Grade 1 or 2.

The most common treatment-related AEs reported by investigators (≥15 percent) were increased aspartate aminotransferase (AST), anemia, increased alanine aminotransferase (ALT), constipation, hypertension and neutropenia. Investigator-reported Grade 3 or higher treatment-related AEs (≥5 percent) were hypertension, neutropenia and anemia. Only 4 percent of patients discontinued pralsetinib due to treatment-related AEs.

These updated data for pralsetinib are being reported in two presentations at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program Annual Meeting, including a poster discussion presentation on trial results in RET fusion-positive NSCLC (Abstract Number: 9515) and an oral presentation on trial results in other RET fusion-positive cancers (Abstract Number: 109). Copies of the data presentations are available in the "Science—Publications and Presentations" section of Blueprint Medicines’ website at www.BlueprintMedicines.com.

Conference Call Information

Blueprint Medicines will host a live webcast today beginning at 8:30 a.m. ET to discuss updated data from the ARROW trial of pralsetinib in RET fusion-positive cancers. To access the live call, please dial (855) 728-4793 (domestic) or (503) 343-6666 (international) and refer to conference ID 8585078. A webcast of the conference call will be available under "Events and Presentations" in the Investors & Media section of Blueprint Medicines’ website at View Source The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the conference call and will be available for 30 days following the call.

About the Clinical Development Program in RET-Altered Cancers

Blueprint Medicines is pursuing a broad development program for pralsetinib in patients with RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (MTC), RET-fusion thyroid cancer and other advanced solid tumors. The Phase 1/2 ARROW trial and the Phase 3 AcceleRET Lung trial are currently ongoing.

ARROW is designed to evaluate the safety, tolerability and efficacy of pralsetinib in adults with RET-altered cancers. The trial consists of two parts: a dose escalation portion, which is complete, and an expansion portion in patients treated at 400 mg QD. The study’s objectives include assessing response, pharmacokinetics, pharmacodynamics and safety. The trial is enrolling patients at multiple sites in the United States, European Union and Asia.

The primary objective of the AcceleRET Lung trial is to evaluate the potential of pralsetinib to extend progression-free survival compared to platinum-based chemotherapy, with or without pembrolizumab, as a first-line treatment for RET fusion-positive NSCLC. The trial is designed to enroll approximately 250 patients randomized to receive either pralsetinib or the investigator’s choice of platinum-based chemotherapy regimen with or without pembrolizumab. Patients randomized to the control arm may crossover upon progression to receive pralsetinib. Additional endpoints include overall survival, ORR and DOR. Multiple trial sites are active or planned in North America, Europe and Asia.

Patients and physicians interested in the ARROW or AcceleRET Lung trial can contact the Blueprint Medicines study director at [email protected] or 1-617-714-6707. Additional information is available at www.BlueprintClinicalTrials.com/ARROW and www.clinicaltrials.gov.

About RET-Altered Solid Tumors

RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and MTC. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET alterations are observed at low frequencies in colorectal, breast, pancreatic and other cancers, and RET fusions have been observed in patients with treatment-resistant EGFR-mutant NSCLC.

There are several approved multi-kinase inhibitors (MKIs) with RET activity being evaluated in clinical trials. To date, clinical activity attributable to RET inhibition has been uncertain for these approved MKIs, likely due to insufficient inhibition of RET and off-target toxicities. There is a need for precision therapies that provide durable clinical benefit by selectively targeting RET alterations and anticipated resistance mutations.

About Pralsetinib

Pralsetinib is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET alterations. Blueprint Medicines is developing pralsetinib for the treatment of patients with RET-altered NSCLC, thyroid cancer and other solid tumors. The FDA has granted Breakthrough Therapy Designation to pralsetinib for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy, and RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Pralsetinib was designed by Blueprint Medicines’ research team, leveraging the company’s proprietary compound library. In preclinical studies, pralsetinib consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and predicted resistance mutations. In addition, pralsetinib demonstrated markedly improved selectivity for RET compared to pharmacologically relevant kinases, including approximately 80-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, pralsetinib has the potential to overcome and prevent the emergence of clinical resistance. Blueprint Medicines believes this approach will enable durable clinical responses across a diverse range of RET alterations, with a favorable safety profile.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of pralsetinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for pralsetinib in the rest of the world.

On May 29, 2020 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it has entered into a clinical trial collaboration agreement with a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, U.S.A., known as MSD outside the United States and Canada, to evaluate the combination of DS-1062, a TROP2 directed DXd antibody drug conjugate (ADC), and KEYTRUDA (pembrolizumab) in patients with previously-treated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (Press release, Daiichi Sankyo, MAY 29, 2020, https://www.businesswire.com/news/home/20200529005050/en/Daiichi-Sankyo-Announces-Clinical-Research-Collaboration-Evaluate [SID1234558722]).

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There are no TROP2 directed therapies and no ADCs currently approved for treatment of NSCLC, which frequently overexpresses the TROP2 protein.1

"Strategic research collaborations like this support our goal of developing our TROP2 directed DXd ADC in combination with immune checkpoint inhibitors to improve upon the current standard of care therapies across a wide range of NSCLC subtypes," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "We look forward to evaluating the safety and efficacy of DS-1062 in combination with KEYTRUDA as a potential combination therapy strategy to advance treatment outcomes for patients with metastatic NSCLC without mutations known to drive cancer growth."

About the Study

Under the terms of the agreement, Daiichi Sankyo will conduct a multicenter, two-part, open-label, non-randomized, phase 1b study of DS-1062 in combination with KEYTRUDA in patients with advanced or metastatic NSCLC without actionable genomic alterations and previously treated with platinum-based chemotherapy with or without immunotherapy. Patients need to have been previously treated with one regimen of a PD-1/PD-L1 directed immunotherapy, except if patients have a PD-L1 proportion score of <1%.

The first part of the study (dose escalation) will evaluate the safety and tolerability of increasing doses of DS-1062 with a fixed dose of KEYTRUDA to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). The second part of the study (dose expansion) will evaluate the safety and tolerability of DS-1062 at the RDE in combination with KEYTRUDA.

The primary endpoints of the study are safety and tolerability of the maximum tolerated dose/recommended expansion dose of DS-1062 in combination with KEYTRUDA. Secondary endpoints include objective response rate (ORR), duration of response, disease control rate, clinical benefit rate, progression-free survival, time to tumor response, best percentage change in sum of diameters of the tumor as assessed by investigator, overall survival, and pharmacokinetic and immunogenicity parameters. Patients with documented wild-type EFGR and ALK mutations, alterations in ROS1, NTRK, BRAF, or other known actionable mutations are not eligible for the study.

The study is expected to enroll approximately 60 patients in the U.S. and Japan. Additional details of the agreement were not disclosed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.

Unmet Need in Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide; there were an estimated 2.1 million new cases of lung cancer diagnosed in 2018 and 1.8 million deaths.2

NSCLC accounts for approximately 80 to 85 percent of all lung cancers.3 The majority of patients diagnosed with advanced NSCLC have traditionally received platinum-based chemotherapy as first-line treatment; the introduction of immune checkpoint inhibitors and targeted therapies in recent years has created new options.3 These newer types of agents may be recommended in first or subsequent lines of treatment based on genetic and biomolecular profiling of tumors.4 For patients whose cancer continues to progress on available regimens, new and novel therapeutics are needed.4

About TROP2

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is overexpressed in many cancers; high TROP2 expression has been identified in a majority of NSCLCs.1 Overexpression of TROP2 is associated with decreased patient survival.5 TROP2 is recognized as a promising molecular target for therapeutic development.5 No TROP2 directed therapies are currently approved for treatment of NSCLC.

About DS-1062

DS-1062 is one of three lead DXd antibody drug conjugates (ADCs) in the oncology pipeline of Daiichi Sankyo. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

DS-1062 is comprised of a humanized anti-TROP2 monoclonal antibody attached to a topoisomerase I inhibitor payload by a tetrapeptide-based linker with a customized drug-to-antibody ratio (DAR) of four to optimize the benefit-risk ratio for the intended patient population. Preclinical studies have demonstrated that DS-1062 selectively binds to the TROP2 receptor on the surface of a tumor cell. It is proposed that DS-1062 is then internalized into the cancer cell where lysosomal enzymes break down the tetrapeptide-based linker and release the DXd payload.

DS-1062 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise

The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our DXd antibody drug conjugate (ADC) technology, our powerful research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.

On May 29, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the final results from the GENUINE Phase 3 study evaluating the combination of ublituximab, the Company’s novel glycoengineered anti-CD20 monoclonal antibody, plus ibrutinib compared to ibrutinib alone in patients with previously treated high-risk chronic lymphocytic leukemia (CLL) at the 56thAmerican Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, TG Therapeutics, MAY 29, 2020, View Source [SID1234558738]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We are extremely pleased with the final results of the GENUINE Phase 3 trial presented today. Not only is this the first randomized trial to show a PFS benefit with the addition of an anti-CD20 antibody to ibrutinib, compared to ibrutinib monotherapy, it was also highly encouraging to see the combination significantly improved overall response rate, complete response rate, and importantly increased the rates of undetectable minimal residual disease." Mr. Weiss continued, "We believe these data support the potential of combination therapies to improve outcomes for patients with high risk CLL, especially those with 17p deletion/TP53 mutation, who continue to progress more rapidly than those without high risk cytogenetics."

Details of the data presentation are included below.

Presentation Title: Effect of Adding Ublituximab to Ibrutinib on PFS, ORR, and MRD Negativity in Previously Treated High-Risk Chronic Lymphocytic Leukemia: Final Results of the GENUINE Phase III Study

The GENUINE trial is an open-label, multicenter, randomized, Phase III study in relapsed or refractory high-risk CLL (del17p, del11q, or TP53mutation). This presentation includes data from 117 patients treated with either ublituximab plus ibrutinib (n=59) or ibrutinib alone (n=58). As of the cut-off date of September 1, 2019, patients had a median follow-up time of 41.9 months. The primary endpoint for this trial was overall response rate (ORR) as determined by an independent review committee (IRC). The secondary endpoints included progression free survival (PFS) and complete response (CR) rate as determined by an IRC, and undetectable minimal residual disease (uMRD) assessed by central lab.

Efficacy and safety highlights include:

The addition of ublituximab to ibrutinib compared to ibrutinib monotherapy significantly improved ORR (93% compared to 78%; p=0.019), complete response/complete response with incomplete blood count recovery (CR/CRi) rate (20% vs. 5%; p=0.024), and increased rates of uMRD (46% vs. 7%; p<0.001) in patients with relapsed/refractory CLL with high-risk cytogenetics
At a median follow-up of 41.9 months, median PFS was not reached in the ublituximab plus ibrutinib arm and was 35.9 months in the ibrutinib monotherapy arm (hazard ratio 0.46), with del17p/TP53mut patients seeing the greatest difference in PFS
The addition of ublituximab to ibrutinib did not significantly alter the known safety profile of ibrutinib however the combination resulted in slightly higher rates of neutropenia (36% compared to 21%) and atrial fibrillation (14% compared to 7%)
The data presented is available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

ABOUT THE GENUINE PHASE 3 STUDY
The GENUINE Phase 3 study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of ublituximab plus ibrutinib compared to ibrutinib alone in adult patients with high-risk chronic lymphocytic leukemia (CLL) who received at least one prior therapy for their disease.

Patients received ibrutinib orally at 420 mg once daily in both arms and in the combination arm those patients also received intravenous infusions of ublituximab at 900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6. Patients in the combination arm who had not progressed received quarterly infusions of ublituximab maintenance at 900 mg.