On June 17, 2019 T Medical Technologies, Inc., a company dedicated to improving the lives of patients with brain tumors, reported the presentation of clinical data from a prospective study of GammaTile Therapy in patients with previously irradiated intracranial neoplasms (brain tumors) at the American Brachytherapy Society (ABS) 2019 Annual Meeting in Miami (Press release, GT Medical Technologies, JUN 17, 2019, View Source [SID1234537120]). These data reinforce the safety profile of GammaTile Therapy, a surgically targeted radiation therapy (STaRT) that is designed to delay tumor regrowth for patients with recurrent intracranial neoplasms (brain tumors).

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The company also announced that David Brachman, M.D., co-founder and CTO of GT MedTech, received the prestigious Judith Stitt Best Abstract Award for his abstract Surgically Targeted Radiation Therapy: Safety Profile of Collagen Tile Brachytherapy in 79 Recurrent, Previously Irradiated Intracranial Neoplasms on a Prospective Clinical Trial. Only four abstracts every year – out of hundreds of submissions – are selected by the ABS’s scientific committee for this recognition.

GammaTile is an FDA-cleared therapy for patients with recurrent intracranial neoplasms (brain tumors) including primary (benign or malignant) and metastatic tumors. Placed directly at the site of the tumor cavity during the last few minutes of excision surgery, GammaTile Therapy is a new approach that immediately begins targeting residual tumor cells, before they can replicate. Designed to help protect healthy brain tissue and facilitate rapid, accurate placement during the procedure, the therapy features a bioresorbable, conformable, 3D-collagen tile and uniform radiation source.

The prospective, single-arm study evaluated the safety profile of GammaTile Therapy in combination with tumor resection surgery in 79 recurrent brain tumors of various types, including gliomas, meningiomas, and brain metastases. Results from the study showed that GammaTile Therapy improves local tumor control compared to currently available treatments. The study also showed a low rate of adverse events, with wound infection occurring in 2.5% of tumors and radiation-related brain changes occurring in 8% of treated patients during the follow-up period. These findings suggest that GammaTile Therapy is a viable radiation therapy option for the challenging cohort of patients with recurrent brain tumors.

"These data further support the safety profile and efficacy of GammaTile Therapy for patients with brain tumors," said Dr. Brachman. "This therapy is designed to meet a significant unmet need for patients who may not be candidates for other forms of radiation therapy, or for whom surgery is not a viable option without effective adjuvant therapy. We are encouraged by these data, which build on our body of evidence supporting the safety and efficacy of this therapy."

GammaTile Therapy offers advantages over the most common treatment for patients undergoing surgery for recurrent brain tumors: a course of External Beam Radiation Therapy (EBRT), which requires daily treatments for up to six weeks. Some patients may not be candidates for EBRT. Once the disease has returned, many people with recurrent brain tumors have already received levels of radiation therapy that make the risk of additional external beam radiation outweigh the potential benefits. Additionally, those patients who are potentially candidates for EBRT typically have to wait two weeks or more for surgical wound healing before beginning treatment, giving any residual tumor cells a chance to replicate.

Initial data from this study were published this year in the Journal of Neurosurgery (JNS) demonstrating that GammaTile therapy is a safe and effective new option proven to delay tumor progression in patients with previously treated, aggressive meningiomas, the most common type of primary brain tumor. Additional data from this study supporting the safety and efficacy of GammaTile Therapy for various tumor types were presented in April at the American Association of Neurological Surgeons Annual Meeting, affirming that this therapy could help expand options for brain tumors that are challenging to treat.

About GammaTile Therapy

GammaTile Therapy is an FDA-cleared, surgically targeted radiation therapy (STaRT) that is designed to delay tumor regrowth for patients with brain tumors. Featuring a bioresorbable, conformable, 3D-collagen tile and uniform radiation source, GammaTile Therapy is placed at the end of excision surgery so that it immediately begins to target residual tumor cells while limiting the impact of radiation on healthy brain tissue. Because the therapy is implanted at the end of surgery, patients treated with GammaTile Therapy require no additional trips to the hospital or clinic for radiation therapy.

On June 17, 2019 Pfizer Inc. (NYSE: PFE) and Array BioPharma Inc. (NASDAQ: ARRY) reported that they have entered into a definitive merger agreement under which Pfizer will acquire Array, a commercial stage biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule medicines to treat cancer and other diseases of high unmet need. Pfizer has agreed to acquire Array for $48 per share in cash, for a total enterprise value of approximately $11.4 billion (Press release, Array BioPharma, JUN 17, 2019, View Source [SID1234537105]). The Boards of Directors of both companies have approved the merger.

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This press release features multimedia. View the full release here: View Source

Array’s portfolio includes the approved combined use of BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) for the treatment of BRAFV600E or BRAFV600K mutant unresectable or metastatic melanoma. The combination therapy has significant potential for long-term growth via expansion into additional areas of unmet need and is currently being investigated in over 30 clinical trials across several solid tumor indications, including the Phase 3 BEACON trial in BRAF-mutant metastatic colorectal cancer (mCRC).

In the U.S., colorectal cancer is the third most common type of cancer in men and women. An estimated 140,250 patients were diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease each year.1BRAF mutations are estimated to occur in up to 15% of colorectal cancer cases and represent a poor prognosis for these patients.

"Today’s announcement reinforces our commitment to deploy our capital to bring breakthroughs that change patients’ lives while creating shareholder value," said Albert Bourla, chief executive officer of Pfizer. "The proposed acquisition of Array strengthens our innovative biopharmaceutical business, is expected to enhance its long-term growth trajectory, and sets the stage to create a potentially industry-leading franchise for colorectal cancer alongside Pfizer’s existing expertise in breast and prostate cancers."

In addition to the combination therapy for BRAF-mutant metastatic melanoma, Array brings a broad pipeline of targeted cancer medicines in development, as well as a portfolio of out-licensed potentially best-in-class and/or first-in-class medicines, which are expected to generate significant royalties over time.

"We are incredibly proud that Pfizer has recognized the value Array has brought to patients and our remarkable legacy discovering and advancing molecules with great potential to impact and extend the lives of patients in critical need," said Ron Squarer, Array chief executive officer. "Pfizer shares our commitment to patients and a passion for advancing science to develop even more options for individuals with unmet needs. We’re excited our team will have access to world-class resources and a broader research platform to continue this critical work."

In May 2019, Array announced results from the interim analysis of the Phase 3 BEACON mCRC trial: The second-or-third-line treatment with the BRAFTOVI triplet combination (BRAFTOVI + MEKTOVI + cetuximab) showed statistically significant improvement in overall response rate and overall survival compared to the control group, reducing the risk of death by 48%. The triplet combination could be the first chemotherapy-free, targeted regimen for patients with BRAF-mutant mCRC. Array intends to submit these data for regulatory review in the United States in the second half of 2019.

"We are very excited by Array’s impressive track record of successfully discovering and developing innovative small-molecules and targeted cancer therapies," said Mikael Dolsten, Pfizer chief scientific officer and president, Worldwide Research, Development and Medical. "With Array’s exceptional scientific talent and innovative pipeline, combined with Pfizer’s leading research and development capabilities, we reinforce our commitment to advancing the most promising science, regardless of whether it is found inside or outside of our labs."

Upon the close of the transaction, Array’s employees will join Pfizer and continue to be located in Cambridge, Massachusetts and Morrisville, North Carolina, as well as Boulder, Colorado, which becomes part of Pfizer’s Oncology Research & Development network in addition to La Jolla, California and Pearl River, New York.

Pfizer expects to finance the majority of the transaction with debt and the balance with existing cash. The transaction is expected to be dilutive to Pfizer’s Adjusted Diluted EPS by $0.04 -$0.05 in 2019, $0.04 -$0.05 in 2020, neutral in 2021, and accretive beginning in 2022, with additional accretion and growth anticipated thereafter. Pfizer will provide any appropriate updates to its current 2019 guidance in conjunction with its third quarter 2019 earnings release.

Under the terms of the merger agreement, a subsidiary of Pfizer will commence a cash tender offer to purchase all outstanding shares of Array common stock for $48 per share in cash for a total enterprise value of approximately $11.4 billion. The closing of the tender offer is subject to customary closing conditions, including regulatory approvals and the tender of a majority of the outstanding shares of Array common stock (on a fully-diluted basis). The merger agreement contemplates that Pfizer will acquire any shares of Array that are not tendered into the offer through a second-step merger, which will be completed promptly following the closing of the tender offer. Pfizer expects to complete the acquisition in the second half of 2019.

Pfizer’s financial advisors for the transaction were Guggenheim Securities, LLC, and Morgan Stanley & Co. LLC, with Wachtell, Lipton, Rosen & Katz acting as its legal advisor. Centerview Partners served as Array’s exclusive financial advisor, while Skadden, Arps, Slate, Meagher & Flom LLP served as its legal advisor.

Conference Call

Pfizer Inc. invites investors and the general public to view and listen to a webcast of a live conference call with investment analysts at 9:00 a.m. EDT on Monday, June 17, 2019.

To view and listen to the webcast visit Pfizer’s web site at www.pfizer.com/investorsor directly at View Source Information on accessing and pre-registering for the webcast will be available at www.pfizer.com/investors beginning today. Participants are advised to pre-register in advance of the conference call.

You can listen to the conference call by dialing either (855) 895-8759 in the United States or Canada or (503) 343-6044 outside of the United States and Canada. The password is "Analyst Call." Please join the call five minutes prior to the start time to avoid operator hold times.

Pfizer Inc.: Breakthroughs that change patients’ lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

On June 17, 2019 Resolution Bioscience, Inc., reported the publication of a blinded performance evaluation between two cell-free DNA (cfDNA) next-generation sequencing (NGS) assays (Press release, Resolution Bioscience, JUN 17, 2019, View Source [SID1234537121]). The publication reports that the team of scientists, led by lung cancer researchers and clinicians at Dana-Farber Cancer Institute, found that the Resolution ctDx-Lung assay identified more actionable gene fusion mutations than Guardant Health’s Guardant360 test. The peer-reviewed manuscript, "Sensitivity of next-generation sequencing assays detecting oncogenic fusions in plasma cell-free DNA," was released online ahead of publication in Lung Cancer.

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Plasma genotyping has shown the ability to identify actionable, targetable mutations to drive personalized therapy for patients with advanced non-small cell lung cancer (NSCLC). However, leading commercial platforms have generated variable results when detecting complex variations, such as oncogenic gene fusions or copy number variations. In this comparison study, a cohort of 169 NSCLC patients with Guardant360 plasma results was screened for the presence of gene fusions based on previous tumor tissue analysis. Scientists at Dana-Farber used the Resolution kit in their lab to analyze the plasma of 16 patients who had a rearrangement in their tumor. All personnel involved in sample analysis were blinded to tumor genotype and Guardant360 results.

The Resolution assay detected 13 out of 16 (81.3%) fusions (allele frequency range 0.17-62.8%), while the Guardant360 test detected only seven (43.8%) fusions (allele frequency range 0.3-8.2%). For cases detected by both assays, the Resolution technology identified the mutation at a median of 7% higher allele frequency, which is indicative of a higher capture rate of breakpoint bearing cfDNA that increases overall sensitivity. For the six patients in which a fusion was detected by the Resolution assay but not by Guardant360, the average time to treatment discontinuation was 15.2 months (full range of 3-34 months).

"The Resolution liquid biopsy platform is designed to provide a fast, accurate, and non-invasive solution for mutationally comprehensive tumor genotyping," said Mark Li, CEO of Resolution Bioscience. "While this was a small study, we measure our success one patient at a time. Two patients with a fusion undetected by Guardant360 were on treatment for more than 30 months."

Dana-Farber scientists hypothesized that the Resolution assay offers more efficient hybridization to cfDNA fragments due to its use of tiled, short (˜40 nt) capture probes rather than more common 120 nt probes.

"Our targeted sequencing platform was designed from the ground up for analysis of cfDNA fragments. The shorter probes maintain high specificity while allowing better detection of the low amounts of mutation-bearing fragments often found in plasma," said Li. "Importantly, scientists at the Dana-Farber Cancer Institute performed the assay within their lab, demonstrating the potential of a distributed model."

Scientists presented the early results of this retrospective liquid biopsy comparison study between Resolution’s ctDx-Lung assay and Guardant Health’s Guardant360 test at this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. To view the full manuscript, please visit View Source

About Resolution Bioscience’s Technology

The Resolution liquid biopsy assays are powered by the company’s patented cfDNA NGS analysis platform, which includes proprietary targeted capture NGS chemistry and tightly coupled, cloud-based bioinformatics. Resolution’s technology has now been recognized as novel by the US Food and Drug Administration and has been cited in several important research publications and presentations. For example:

The Resolution HRD assay was recently granted Breakthrough Device Designation by the US Food and Drug Administration (FDA).
The company was the first to demonstrate detection of all four major types of mutations in a blinded clinical study led by scientists at Dana-Farber Cancer Institute. The team determined the assay has the potential to be implemented broadly for patient care and translational research.
Resolution was also the first company to demonstrate gene deletion detection in cfDNA in a study led by scientists at Vanderbilt University in small cell lung cancer. The team determined that cfDNA sequencing allows for improved monitoring of disease burden, depth of response to treatment, and timely warning of disease relapse in patients.
Resolution recently published 97% clinical response data with Memorial Sloan Kettering Cancer Center for non-small cell lung cancer patients who received plasma-directed therapy selection from Resolution’s assay. With more than 950 patients enrolled, the ongoing study is the largest prospective study of stage II, III, or IV NSCLC aimed at demonstrating clinical response and outcomes based upon plasma-directed therapy selection.
In a recent AstraZeneca publication, Resolution had the highest positive predictive value (PPV) and lowest false positive rate amongst four leading NGS liquid biopsy companies in a blinded comparison study.

On June 17, 2019 Viela Bio reported the successful completion of a $75 million private placement of its Series B preferred stock, bringing the total capital raised since the Company’s launch in February 2018 to more than $300 million (Press release, Viela Bio, JUN 17, 2019, View Source [SID1234539161]). The financing round was led by HBM Healthcare Investments, and additional new investors participating included Viking Global Investors, Cormorant Asset Management, Terra Magnum Capital Partners, Goldman Sachs, and Barer & Son Capital. Existing investors participating included Temasek.

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"We are pleased that our ongoing development of our clinical programs continues to attract capital from leading healthcare investors. This financing will support our upcoming regulatory milestone—the anticipated filing of our Biologics License Application with the U.S. FDA for our lead product candidate, inebilizumab, for the treatment of neuromyelitis optica spectrum disorder, or NMOSD," said Bing Yao, Ph.D. Executive Chairman and Chief Executive Officer. "NMOSD is a severe, debilitating, and sometimes fatal neurological disease for which there is currently no approved treatment. While our priority is to serve this patient population through the successful approval and launch of inebilizumab, we believe this financing also puts us in a strong position to pursue additional new indications with inebilizumab. Furthermore, we believe this financing will allow us to advance the entirety of our clinical pipeline, which is comprised of several additional clinical candidates for a range of rare autoimmune and inflammatory diseases."

On June 17, 2019 Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), a biopharmaceutical company focused on developing and commercializing medicines seeking to improve the survival and quality of life of cancer patients, reported that two posters highlighting clinical data for COPIKTRA (duvelisib) in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2019 Annual Meeting which took place June 13-16, 2019, in Amsterdam (Press release, Verastem, JUN 17, 2019, View Source;p=RssLanding&cat=news&id=2401532 [SID1234537106]). One poster describes results from a post-hoc analysis evaluating the effect of COPIKTRA on lymphocytosis in patients with relapsed or refractory CLL/SLL from the Phase 3 DUO study, including patients with high-risk factors. The other poster describes dose modification data from patients with relapsed or refractory CLL/SLL in the DUO study.

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COPIKTRA, a targeted oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, received approval as monotherapy from the U.S. Food and Drug Administration (FDA) in September 2018 for the treatment of patients with relapsed or refractory CLL/SLL after at least two prior therapies.

"Duvelisib is a potent oral dual inhibitor of PI3K-delta and -gamma with clinical activity in patients with CLL/SLL after at least two prior therapies," said Hagop Youssoufian, MSc, M.D., Head of Medical Strategy at Verastem Oncology. "In a post-hoc analysis authored by Dr. Barrientos and colleagues, duvelisib induced rapid and transient lymphocytosis that was associated with a reduction in lymphadenopathy, including in high-risk patients. Notably, duvelisib also resulted in resolution of lymphocytosis at up to 21 weeks, and the majority of patients achieved a lymph node response and also achieved rapid shrinkage of their lymph nodes."

Patterns of Duvelisib-Induced Lymphocytosis in Patients with Relapsed/Refractory CLL/SLL, Including Those with High-Risk Factors

In this study, researchers aimed to characterize the clinical profile and kinetics associated with duvelisib-related lymphocytosis. Lymphocytosis is an increase in the number of lymphocytes (white blood cells) in the blood and is a recognized biological marker of treatment with B-cell receptor pathway inhibitors. Similar to ibrutinib and idelalisib, duvelisib treatment induces lymphocytosis in patients with CLL. This post hoc analysis defined response in patients (n=158) with relapsed or refractory CLL/SLL, including high-risk subgroups, which were characterized by unmutated IGHV (n=110), 17p deletion/TP53 mutation (n=48), 11q deletion (n=38), and bulky disease (n=74).

Of 158 patients treated with duvelisib, 78% experienced lymphocytosis. Median time to onset of lymphocytosis was one week across all patients, including patients in the high-risk subgroups. Median time to resolution of lymphocytosis was 14 weeks, with a 50% reduction from baseline at 21 weeks. Similar results were observed regardless of high-risk status. Rapid shrinkage of lymph nodes was noted, with 86% of patients achieving lymph node response. Among patients who achieved a response with duvelisib at first or second assessment, 78% and 86%, respectively, experienced lymphocytosis; median time to resolution of lymphocytosis in these patients was 12 and 18 weeks, respectively. Prolonged lymphocytosis (for >12 months) occurred in 12 patients (8%). The overall response rate in patients with prolonged lymphocytosis was 83%. Of note, the median PFS was similar among patients with and without prolonged lymphocytosis; 22.1 months (95% CI, 12.9-27.6), compared to 24 months (95% CI, 20.5-NE), respectively. Overall, there were low rates of tumor lysis syndrome (1 patient; 0.6%). These results showed that duvelisib monotherapy induced rapid and transient lymphocytosis temporally associated with a reduction in lymphadenopathy in patients with relapsed or refractory CLL/SLL.

Effect of Dose Modification on Response to COPIKTRA in Patients with Relapsed or Refractory CLL/SLL in the Phase 3 DUO Study

The randomized, multicenter, open-label, Phase 3 DUO study, compared COPIKTRA versus ofatumumab in 319 adult patients with CLL (n=312) or SLL (n=7) after at least one prior therapy. The study randomized patients with a 1:1 ratio to receive either COPIKTRA 25mg twice daily until disease progression or unacceptable toxicity, or ofatumumab, an approved standard of care treatment for use in CLL/SLL, for 7 cycles. This analysis examined dose modification patterns and their impact on response to COPIKTRA. Dose interruptions or dose reductions to 15mg, 10mg or 5mg twice daily were permitted per study protocol to manage treatment-emergent adverse events (TEAEs). Responses were assessed per an Independent Review Committee.

Among the 158 COPIKTRA-treated patients in the DUO study, the median duration of exposure was 11.6 months, versus 5.3 months for patients treated with ofatumumab. The most common cause of dose interruption was diarrhea (23%), followed by neutropenia (12%) and pneumonia or colitis (11% each). Among responders (n=118), median time to first response on COPIKTRA was 1.9 months and the estimated median duration of response was 11.1 months. Median time to first dose interruption was 3.9 months and median duration of dose interruption was 15 days (range 1 to 133 days). Response to COPIKTRA was improved or maintained in most patients evaluated for response who had at least one dose interruption for >1 week (84%) or >2 weeks (82%) followed by at least 3 weeks on COPIKTRA. In a landmark analysis, median PFS was similar in patients with dose interruptions and those without dose interruptions for >1 week (17.8 versus 16.3 months) or >2 weeks (17.8 versus 16.3 months) within the first 3 months. The median time to dose reduction after a complete response or partial response was 5.6 months (n=25) and median duration was 3.4 months. Median time to onset across adverse events of special interest (AESIs) after starting COPIKTRA ranged from 2.2 to 4.3 months. Median time to resolution was within 4 weeks across AESIs. Proportions of patients experiencing AESIs were stable or decreased over time after 3-6 months: 0-3 months, 64%; >3-6 months, 63%; >6-9 months, 47%; >9-12 months, 52%, and seldom led to discontinuation of COPIKTRA (≤10%). These findings support the thesis that dose interruptions or dose reductions may be useful in managing TEAEs with COPIKTRA and that dose interruptions of >1-2 weeks or more did not appear to significantly impact response to COPIKTRA or PFS.

PDF copies of these poster presentations are available here.

Details for the EHA (Free EHA Whitepaper) 2019 poster presentations are as follows:

Title: Effect of dose modifications on response to duvelisib in patients with relapsed/refractory (R/R) CLL/SLL in the DUO trial
Lead author: Paolo Ghia, Università Vita-Salute San Raffaele
Session: 6. Chronic lymphocytic leukemia and related disorders – Clinical
Abstract #: PS1157
Title: Patterns of duvelisib-induced lymphocytosis in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic leukemia including those with high-risk factors treated in the DUO trial
Lead author: Jacqueline Barrientos, Zucker School of Medicine at Hofstra/Northwell
Session: 6. Chronic lymphocytic leukemia and related disorders – Clinical
Abstract #: PS1160
Important Safety Information

WARNING: FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and PNEUMONITIS

•Fatal and/or serious infections occurred in 31% of COPIKTRA-treated patients. Monitor for signs and symptoms of infection. Withhold COPIKTRA if infection is suspected.

•Fatal and/or serious diarrhea or colitis occurred in 18% of COPIKTRA-treated patients. Monitor for the development of severe diarrhea or colitis. Withhold COPIKTRA.

•Fatal and/or serious cutaneous reactions occurred in 5% of COPIKTRA-treated patients. Withhold COPIKTRA.

•Fatal and/or serious pneumonitis occurred in 5% of COPIKTRA-treated patients. Monitor for pulmonary symptoms and interstitial infiltrates. Withhold COPIKTRA.

WARNINGS AND PRECAUTIONS

Infections: Serious, including fatal (4%), infections occurred in 31% of patients receiving COPIKTRA (N=442). The most common serious infections were pneumonia, sepsis, and lower respiratory infections. Median time to onset of any grade infection was 3 months, with 75% of cases occurring within 6 months. Treat infections prior to initiation of COPIKTRA. Advise patients to report new or worsening signs and symptoms of infection. Cases of Pneumocystis jirovecii pneumonia (PJP) (1%) and cytomegalovirus (CMV) reactivation/infection (1%) occurred in patients taking COPIKTRA. Provide prophylaxis for PJP during treatment and following completion of treatment until the absolute CD4+ T cell count is greater than 200 cells/µL. Consider prophylactic antivirals during COPIKTRA treatment to prevent CMV infection including CMV reactivation.

Diarrhea or Colitis: Serious, including fatal (<1%), diarrhea or colitis occurred in 18% of patients receiving COPIKTRA (N=442). Median time to onset of any grade diarrhea or colitis was 4 months, with 75% of cases occurring by 8 months. The median event duration was 0.5 months. Advise patients to report any new or worsening diarrhea.

Cutaneous Reactions: Serious, including fatal (<1%), cutaneous reactions occurred in 5% of patients receiving COPIKTRA (N=442). Fatal cases included drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN). Median time to onset of any grade cutaneous reaction was 3 months with a median event duration of 1 month. Presenting features for the serious events were primarily described as pruritic, erythematous, or maculo-papular. Less common presenting features include exanthem, desquamation, erythroderma, skin exfoliation, keratinocyte necrosis, and papular rash. Advise patients to report new or worsening cutaneous reactions.

Pneumonitis: Serious, including fatal (<1%), pneumonitis without an apparent infectious cause occurred in 5% of patients receiving COPIKTRA (N=442). Median time to onset of any grade pneumonitis was 4 months with 75% of cases occurring within 9 months. The median event duration was 1 month with 75% of cases resolving by 2 months.

Hepatotoxicity: Grade 3 and 4 ALT and/or AST elevation developed in 8% and 2%, respectively, of patients receiving COPIKTRA (N=442). Two percent of patients had both an ALT or AST > 3 X ULN and total bilirubin > 2 X ULN. Median time to onset of any grade transaminase elevation was 2 months with a median event duration of 1 month. Monitor hepatic function during treatment with COPIKTRA.

Neutropenia: Grade 3 or 4 neutropenia occurred in 42% of patients receiving COPIKTRA (N=442), with Grade 4 neutropenia occurring in 24% of all patients. Median time to onset of grade ≥3 neutropenia was 2 months. Monitor neutrophil counts at least every 2 weeks for the first 2 months of COPIKTRA therapy, and at least weekly in patients with neutrophil counts < 1.0 Gi/L (Grade 3-4).

Embryo-Fetal Toxicity: COPIKTRA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus and conduct pregnancy testing before initiating COPIKTRA treatment. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose.

ADVERSE REACTIONS

B-cell Malignancies Summary

Fatal adverse reactions within 30 days of the last dose occurred in 8% (36/442) of patients treated with COPIKTRA 25 mg BID. Serious adverse reactions were reported in 289 patients (65%). The most frequent serious adverse reactions that occurred were infection (31%), diarrhea or colitis (18%), pneumonia (17%), rash (5%), and pneumonitis (5%). The most common adverse reactions (reported in ≥20% of patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain and anemia.

CLL/SLL

Fatal adverse reactions within 30 days of the last dose occurred in 12% (19/158) of patients treated with COPIKTRA and in 4% (7/155) of patients treated with ofatumumab. Serious adverse reactions were reported in 73% (115/158) of patients treated with COPIKTRA and most often involved infection (38%; 60/158) and diarrhea or colitis (23%; 36/158). The most common adverse reactions with COPIKTRA (≥20% of patients) were diarrhea or colitis, neutropenia, pyrexia, upper respiratory tract infection, pneumonia, rash, fatigue, nausea, anemia and cough.

For specific information on the management of the adverse reactions above, please review Dose Modifications for Adverse Reactions within the full Prescribing Information.

DRUG INTERACTIONS

CYP3A Inducers: Coadministration with a strong CYP3A inducer may reduce COPIKTRA efficacy. Avoid coadministration with strong CYP3A4 inducers.

CYP3A Inhibitors: Coadministration with a strong CYP3A inhibitor may increase the risk of COPIKTRA toxicities. Reduce COPIKTRA dose to 15 mg BID when coadministered with a strong CYP3A4 inhibitor.

CYP3A Substrates: Coadministration of COPIKTRA with sensitive CYP3A4 substrates may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

To report Adverse Reactions, contact FDA at 1-800-FDA-1088 (1-800-332-1088) or www.fda.gov/medwatch and Verastem Oncology at 1-877-7RXVSTM (1-877-779-8786).

Please see accompanying full Prescribing Information, including Boxed Warning.

About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are cancers that affect lymphocytes and are essentially the same disease, with the only difference being the location where the cancer primarily occurs. When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL. The symptoms of CLL/SLL include a tender, swollen abdomen and feeling full even after eating only a small amount. Other symptoms can include fatigue, shortness of breath, anemia, bruising easily, night sweats, weight loss, and frequent infections. However, many patients with CLL/SLL will live for years without symptoms. There are approximately 200,000 patients in the US affected by CLL/SLL with nearly 20,000 new diagnoses this year alone. While there are therapies currently available, real-world data reveals that a significant number of patients either relapse following treatment, become refractory to current agents, or are unable to tolerate treatment, representing a significant medical need. The potential of additional oral agents, particularly as a monotherapy that can be used in the general community physician’s armamentarium, may hold significant value in the treatment of patients with CLL/SLL.

About COPIKTRA (duvelisib)

COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies and relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. COPIKTRA is also being developed by Verastem Oncology for the treatment of peripheral T-cell lymphoma (PTCL), for which it has received Fast Track status, and is being investigated in combination with other agents through investigator-sponsored studies.4 For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.