On October 9, 2018 Oblique Therapeutics, a biotech focused on new medicines for severe diseases with large unmet medical needs, reported that it will present new promising preclinical data for the drug candidate OT-1096 in triple-negative breast cancer (TNBC) at the largest oncology congress in Europe, the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper), held 19-23 October in Munich, Germany (Press release, Oblique Therapeutics, OCT 9, 2018, http://obliquet.com/oblique-therapeutics-present-tumor-growth-inhibition-and-treg-lowering-data-for-ot-1096-in-humanized-mouse-tnbc-model-at-oncology-congress-esmo/ [SID1234530026]).

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The new data of the first-in-class anti-cancer agent OT-1096 shows promising preliminary results with improved tumor growth inhibition compared to pembrolizumab, one of the blockbuster drugs within immunooncology. The humanized TNBC PDX mouse-model, used in this study, allows for the growth of a breast cancer derived from a patient, in the presence of a human immune system. The results suggest that OT-1096 reduces tumor growth by two associated mechanisms; direct cancer cell killing activity by redox system modulation that, in turn, results in a beneficial immunomodulatory action through lowering of regulatory T-cells within the TIL* population as compared to controls. The results warrant further investigations of OT-1096 in TNBC and other aggressive cancers. Treatment with OT-1096 shows no safety or tolerability concerns.

"First of all, it is an honor to be recognized by ESMO (Free ESMO Whitepaper), and we are thrilled to exhibit our promising results for OT-1096 for the first time. Even more so, being part of changing the treatment landscape for cancer at this time is exciting for us: the 2018 Nobel Prize in Medicine was awarded for pioneering work in immunooncology and we see more and more traction and exciting results from novel immunomodulatory small molecules, such as ours, with the capacity to favorably change the immune system inside tumors ," said Prof. Owe Orwar, CEO at Oblique Therapeutics.

TNBC is an aggressive subtype of breast cancer associated with poor prognosis and limited treatment options, and new effective medicines are needed. Globally, two million people are diagnosed with breast cancer every year; of which 10-13 percent has TNBC.

Prof. Owe Orwar, CEO at Oblique Therapeutics, will present a poster (441P) with the title: "OT-1096, a first-in-class immunoactivating small molecule that targets the thioredoxin reductase/thioredoxin axis causes strong tumor growth inhibition by downregulating intratumoral Tregs in a humanized TNBC-PDX model" on Monday 22 October 2018 at 12:45-13:45. The abstract is available through esmo.org: View Source (search: 441P)

For more information, please contact:
Prof. Owe Orwar, CEO
Email: [email protected]

About OT-1096
OT-1096 is a next-generation first-in-class small molecule immunomodulator with anti-cancer activity. The initial clinical focus is on targeting advanced triple-negative breast cancer (TNBC) but the program will be extended to include other forms of metastatic and advanced cancer that fits to the mechanism of action of OT-1096.

On October 9, 2018 Pfizer Inc. (NYSE:PFE) reported its executive team that will report to Albert Bourla, incoming Chief Executive Officer, coincident with the commencement of his new role effective January 1, 2019 (Press release, Pfizer, OCT 9, 2018, View Source [SID1234529943]).

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"We are at a pivotal moment in Pfizer’s history, with Ian Read having positioned the company with a strong portfolio of marketed products, a deep pipeline and the clear potential to accelerate our revenue growth,"
said Bourla. "Given this opportunity to realize this accelerated growth potential, we are creating an executive team that has a proven record of success, an unwavering commitment to the patients we serve, and a clear
value creation initiative. I look forward to working with these outstanding leaders to achieve the full potential of our pipeline and deliver our next stage of growth."

Frank D’Amelio – Chief Financial Officer and Executive Vice President, Global Supply and Business Operations, will also assume the leadership for our manufacturing operations, Pfizer Global Supply (PGS).

Mikael Dolsten – Global President, Worldwide Research and Development, and Medical, will also assume oversight of the Chief Medical Officer’s role.

Michael Goettler – Global President, Established Medicines. As previously announced Michael will lead the Established Medicines business that will operate as an autonomous, stand-alone unit within Pfizer.

Angela Hwang – Group President, Pfizer Innovative Medicines, will become the Group President of Pfizer’s science-based Innovative business responsible for the entire portfolio of innovative medicines.

Rady Johnson – Executive Vice President, Chief Compliance, Quality and Risk Officer, will continue in his role as the Company’s Chief Compliance Officer.

Doug Lankler – Executive Vice President, General Counsel, will continue in his role as the company’s General Counsel.

Freda Lewis-Hall – Executive Vice President, Chief Patient Officer, will assume a new role as Pfizer’s Chief Patient Officer, deploying the resources of the company to advocate on behalf of all patients who rely on Pfizer to deliver new therapies and vaccines.

Rod MacKenzie – Executive Vice President, Chief Development Officer, will expand his responsibilities to include Pfizer’s regulatory affairs function in addition to all late stage development activities.

Dawn Rogers – Executive Vice President, Chief Human Resources Officer, will continue to lead the Human Resources team.

Sally Susman – Executive Vice President, Chief Corporate Affairs Officer, will continue to lead the Corporate Affairs function.

John Young – Group President, Chief Business Officer, will assume a new role, responsible for strategy, business development, portfolio management and valuation activities; business analytics; global commercial operations; and Patient and Health Impact, among others. Pfizer’s Consumer Healthcare business will also report to John.

Given the growing strategic importance of deploying digital technologies in research, discovery and business processes, Pfizer is appointing a Chief Digital Officer responsible for creating and implementing a strategy that accelerates and improves our digital capabilities so we can deliver more value to patients. Lidia Fonseca will join Pfizer’s
Executive Leadership Team in January 2019, as Executive Vice President, Chief Digital and Technology Officer. She is currently the Chief Information Officer and Senior Vice President at Quest Diagnostics.
Previously, she served as SVP at Laboratory Corporation of America, Executive Vice President of Global Operations and Technology at Synarc Incorporated, and held several positions of increasing responsibility at Philips Healthcare.

Executive Vice President and President, PGS, Dr. Kirsten Lund-Jurgensen, will retire at the end of the year after 19 years at Pfizer, and Executive Vice President, Strategy & Commercial Operations, Laurie Olson, will retire effective January 1, 2019, after 32 years at Pfizer.

On October 9, 2018 Nymox Pharmaceutical Corporation (NASDAQ: NYMX) reported its important new long-term clinical trial results from the Company’s 146 patient Phase IIb NX03-0040 Fexapotide (FT) U.S. study for low grade localized prostate cancer (Press release, Nymox, OCT 9, 2018, View Source [SID1234529926]). All patients in the 78 month study had greater than or equal to 56 months from the time of enrollment, with a range of 56 to 78 months. After 78 months, the data shows that men who received the high dose Fexapotide 15mg single dosage treatment had a 73% reduction in the need for surgery or radiotherapy associated with much more favorable biopsy Gleason results compared to controls (p=.0024). There were 5% patients in the entire Fexapotide group (high dose and low dose) who showed increase in their Gleason primary pattern grade in the 78 month study, compared to controls where the incidence of grade 4 or higher primary pattern was 26.3%, a reduction of 81% (p=.0037).

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In the low grade localized prostate cancer trial reported today, Fexapotide triflutate (FT) was administered by a single painless injection directly into the prostate in a simple procedure requiring several minutes or less in an office setting without sedation or anesthesia, and guided by routine ultrasound. FT was injected into the area of the prostate where the cancer was previously detected prior to enrollment in NX03-0040. The patients were then biopsied after 6 weeks and then every 18 months, along with serial PSA measurements and long-term follow-up. After 78 months of study, high dose FT 15mg single treatment resulted in 73% less surgery or radiotherapy associated with Gleason grade progression (p=.0024), and both doses of FT (15mg and 2.5mg) as a group were overall effective (p=.0037). The 15mg dose was more effective than the lower dose. There were 5% patients in the entire FT group who showed increase in their Gleason primary pattern grade in the 78 month study, compared to controls where the incidence of grade 4 or higher primary pattern was 26.3%, a reduction of 81% (p=.0037). After 78 months all recorded instances of surgery or radiotherapy, including elective cases without Gleason upgrades, were decreased by 65.4% (p=.0014) in FT 15mg treated patients compared to the randomized control group. Numerous other parameters were significantly better in the FT treated groups compared to controls. Study NX03-0040 was undertaken starting in 2012 at 44 investigational sites across the U.S. with 146 men with the biopsy confirmed diagnosis of T1c prostate cancer, which is the most common type of low grade localized prostate cancer.

The Company expects to publish full details from this prostate cancer trial in peer review publications as well as participation in upcoming scientific presentations.

Paul Averback, CEO of Nymox, said, "These exciting new results confirm and expand the evidence for the beneficial long-term effect of a virtually painless and safe minimal administration of Fexapotide Triflutate to men with low grade localized prostate cancer. The risk of prostate cancer progression is very significantly reduced in these U.S. clinical trials, based on objective evidence from biopsies and surgery. It is important to emphasize that Fexapotide has also been shown to be associated with a major reduction in the incidence of new prostate cancer in men suffering from BPH (benign prostatic hyperplasia). This additional evidence comes from patients who received FT for their BPH in Nymox’s long-term studies of 977 men with BPH in the U.S. as part of Nymox’s pivotal Phase 3 BPH clinical program. Both 1) the long-term data reported here today involving treatment of biopsy established low grade localized cancers, and 2) the long-term prevention of new confirmed cancer in BPH patients reported previously, together indicate that FT has shown significant efficacy in men for the treatment and prevention of prostate cancer, without the risks and undesirable side effects generally associated with treatment of these conditions."

Dr. Averback added, "These strong results clearly support Management’s ongoing efforts to advance both of the Company’s 2 major clinical programs towards marketing goals. Nymox has taken the first steps toward an anticipated meeting with regulatory authorities concerning planning for registration trials for low grade prostate cancer. There is a global unmet medical need for more effective prostate treatments without the undesirable risks and often permanent side effects of current treatments."

The Company recently published and reported on the long-term safety of re-administration of Fexapotide based on re-injection studies NX02-0020 and NX02-0022 involving 344 men given Fexapotide re-injections in 2 Phase 3 multi-year re-injection safety trials. Re-injection safety data is a key necessity for injection treatments. It is expected for prostate cancer treatment that follow-up and intermittent re-treatments will be needed and desirable for many if not the majority of men who require treatment.

Low grade localized prostate cancer (T1c) represents approximately half of prostate cancers that are diagnosed, and is a very common treatment problem. The Nymox study reported today involves patients with initially Gleason grade 3+3 or lower. These patients are found to have these tumors by biopsy which is usually instituted after finding abnormalities in PSA levels, and/or after abnormal digital rectal examination of the prostate, and/or after the patient has experienced lower urinary tract symptoms or other changes.

Low grade localized prostate cancer represents a therapeutic challenge. Because of its slow growth and low initial level of malignancy, doctors and patients are often reluctant to proceed to invasive surgical treatments or radiotherapy due to the unpleasant and often permanent side effects these treatments cause in the genitourinary tract, such as sexual functional issues and/ or urinary issues. Eventually if and when the tumor progresses, invasive surgical and/or radiotherapeutic procedures become necessary, with greater risk due to the progression. Occasionally the tumors become highly malignant after variable lengths of time. These risks cause understandable anxieties and distress and many men prefer to advance to invasive therapy before running these risks of higher grade cancers.

It is widely acknowledged that a treatment alternative that can destroy or ablate the low grade cancers of the prostate without the dreaded side effects and morbidities, would be a great addition to the armamentarium of the urologist for the benefit of these patients. FT is the leading contender to deliver chemical ablation of low grade localized cancers of the prostate, without major safety risks, and to be capable of safe multiple treatments when necessary. Low grade cancers of the prostate are frequently multifocal and should be expected to require retreatments for the different cancer foci; for cancer foci that are not fully ablated; and for new cancerous foci that develop.

FT is Nymox’s first in class injectable treatment for BPH and low grade localized prostate cancer. The drug is given as a virtually painless injection with no anesthesia, analgesia or catheterization, and is an office procedure which takes a few minutes to administer. FT has been in development for BPH (prostate enlargement) for over 10 years and has been tested by expert clinical trial investigative teams in over 70 distinguished clinical trial centers throughout the US, and has been found after 7 years of prospective placebo controlled double blind studies of treatment of 977 U.S. men with BPH to not only show clinically meaningful and durable relief of BPH symptoms, but also to show a major reduction in the incidence of prostate cancer, compared to placebo and compared to the known and expected normal incidence of the disease. The same clinical BPH program has also shown in a long-term blinded placebo crossover group study an 82-95% reduction in the number of these patients who required surgery after they received crossover FT in the trial, as compared to patients who did not receive FT but instead received crossover conventional approved BPH treatments. The recent results of Phase 3 studies of Fexapotide for BPH were published earlier this year in the World Journal of Urology (May, 2018, Volume 36, Issue 5, pages 801-809) and communicated in numerous podium and symposium presentations to the American Urological Association, most recently at the Annual Meeting of the AUA in San Francisco on May 20, 2018.

Prostate cancer is the most commonly diagnosed cancer in men, other than skin cancer, and is the second leading cause of cancer death for men. Approximately 50% of prostate cancers are initially considered low risk. One of the major problems with the main current prostate treatments for localized prostate cancer (radical prostatectomy, external beam radiation, brachytherapy) is the relatively high incidence of serious sexual and other problems post-treatment. In 9 studies, Fexapotide treatment has been shown to have a negligible significant adverse effect profile post-treatment and no significant adverse effects on sexual or other functions or testosterone levels.

On October 8, 2018 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage immunotherapeutics company, reported it has entered into a purchase agreement with several institutional investors for the purchase of common units and pre-funded units for a combined total of 4,629,630 units in a registered direct offering, for expected gross proceeds of approximately $25 million before placement agent fees and other offering expenses payable by Altimmune (Press release, Altimmune, OCT 9, 2018, View Source [SID1234529900]).

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Each common unit is being sold at a public offering price of $5.40 and consists of one share of common stock and a warrant to purchase one share of common stock at an exercise price of $5.40. Each pre-funded unit is being sold at a public offering price of $5.39 and consists of a pre-funded warrant to purchase one share of common stock at an exercise price of $0.01 per share and a warrant to purchase one share of common stock at an exercise price of $5.40. The public offering price of each pre-funded unit is equal to the public offering price of each common unit being sold to the public in this offering, minus $0.01. The pre-funded warrants will be immediately exercisable and may be exercised at any time until all of the pre-funded warrants are exercised in full. The other warrants will be exercisable immediately and will expire five years from the date of issuance. The terms of the warrants and the pre-funded warrants will be substantially the same as the terms of the warrants and the pre-funded warrants issued in connection with the Company’s public offering completed October 2, 2018 For a summary of the material terms of the warrants and pre-funded warrants, please refer to Exhibit A attached to this press release.

The offering is expected to close on or about October 10, 2018, subject to customary closing conditions. Altimmune intends to use the net proceeds from this offering for the continued advancement of development activities for our clinical-stage product pipeline, general corporate purposes and strategic growth opportunities.

Roth Capital Partners is acting as sole placement agent for the offering.

The securities described above are being offered by Altimmune pursuant to a registration statement on Form S-3 (File No. 333-217034) that was declared effective by the Securities and Exchange Commission (SEC) on April 6, 2017. A final prospectus supplement and an accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s web site at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, by contacting Roth Capital Partners, LLC, Attention: Equity Capital Markets, 888 San Clemente Drive, Suite 400, Newport Beach, California 92660, by telephone at (800) 678-9147 or e-mail at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On October 9, 2018 Verastem, Inc. (Nasdaq: VSTM) (Verastem Oncology or the Company), focused on developing and commercializing medicines to improve the survival and quality of life of cancer patients, reported that the National Comprehensive Cancer Network (NCCN) added COPIKTRA (duvelisib) capsules to the Clinical Practice Guidelines in Oncology (NCCN Guidelines) for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (Press release, Verastem, OCT 9, 2018, View Source;p=RssLanding&cat=news&id=2370741 [SID1234529873]).

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COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma. The U.S. Food and Drug Administration (FDA) granted approval to COPIKTRA on September 24, 2018, for the treatment of adult patients with relapsed or refractory CLL/SLL after at least two prior therapies.

Based on efficacy and safety data from patients with at least two prior lines of therapy who were treated in the randomized, Phase 3 DUO trial (NCT02004522), the NCCN Guidelines now include a Category 2A recommendation for use of COPIKTRA for adult patients whose disease is relapsed or refractory after treatment with at least two prior therapies. The Category 2A recommendation indicates that based upon lower-level evidence, there is uniform NCCN consensus that COPIKTRA is appropriate for these patients.

"We are delighted to announce that the NCCN has now included COPIKTRA into their updated oncology guidelines for patients with relapsed or refractory CLL/SLL following at least two prior therapies," said Robert Forrester, President and Chief Executive Officer of Verastem Oncology. "Physicians use the NCCN guidelines as the standard resource for determining the best course of treatment for patients, and we believe these updated guidelines, along with all of our commercial team’s ongoing efforts, will increase awareness for COPIKTRA and help health care providers make informed decisions for patients battling this difficult to treat advanced cancer."

"Our comprehensive COPIKTRA launch initiative is well underway and proceeding on track. We are pleased to report that COPIKTRA drug product was released into the system within an hour of approval and our fully staffed field team is in place and out making physicians calls. As a result of this skillful execution by our world-class commercial team, our contracted specialty pharmacies are already receiving requests for prescriptions. This is an exciting time for Verastem Oncology as we advance quickly and efficiently to bring this new therapy to the patients and physicians who need it." commented Joseph Lobacki, Executive Vice President and Chief Commercial Officer of Verastem Oncology.

Use of COPIKTRA is associated with a BOXED WARNING for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem Oncology is implementing an informational Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on COPIKTRA.

Additionally, use of COPIKTRA is also associated with adverse reactions which may require dose reduction, treatment delay or discontinuation of COPIKTRA. WARNINGS AND PRECAUTIONS are provided for infections, diarrhea or colitis, cutaneous reactions, pneumonitis, hepatotoxicity, neutropenia, and embryo-fetal toxicity. 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.

Please see important Safety Information provided below and Prescribing Information including BOXED WARNING and Medication Guide at www.COPIKTRAHCP.com/prescribinginformation

COPIKTRA Indication and Usage in CLL/SLL

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory CLL or SLL after at least two prior therapies.

Efficacy in Relapsed or Refractory CLL/SLL

A randomized, multicenter, open-label trial (DUO; NCT02004522) 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 BID until disease progression or unacceptable toxicity, or ofatumumab for 7 cycles.

The approval of COPIKTRA was based on efficacy and safety analysis of patients with at least 2 prior lines of therapy, where the benefit:risk appeared greater in this more heavily pretreated population compared to the overall trial population.

In this subset (95 randomized to COPIKTRA, 101 to ofatumumab), the median patient age was 69 years (range: 40 to 90 years), 59% were male, and 88% had an ECOG performance status of 0 or 1. Forty-six percent received 2 prior lines of therapy, and 54% received 3 or more prior lines. At baseline, 52% of patients had at least one tumor ≥ 5 cm, and 22% of patients had a documented 17p deletion.

During randomized treatment, the median duration of exposure to COPIKTRA was 13 months (range: 0.2 to 37), with 80% of patients receiving at least 6 months and 52% receiving at least 12 months of COPIKTRA. The median duration of exposure to ofatumumab was 5 months (range: < 0.1 to 6).

Efficacy was based on progression-free survival (PFS) as assessed by an Independent Review Committee (IRC). Other efficacy measures included overall response rate (ORR). Efficacy of COPIKTRA compared to ofatumumab specifically in patients treated with at least two prior therapies is below.

Abbreviations: CR = complete response; IRC = Independent Review Committee; PFS = progression-free survival; PR = partial response; SE = standard error

a Kaplan-Meier estimate

b Standard Error of ln(hazard ratio) = 0.2

c IWCLL or revised IWG response criteria, with modification for treatment-related lymphocytosis

Important Safety Information

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

See full prescribing information for complete boxed warning

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 (18/442; 4%), infections occurred in 31% of patients receiving COPIKTRA 25 mg BID (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 (range: 1 day to 32 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. For grade 3 or higher infection, withhold COPIKTRA until infection is resolved. Resume COPIKTRA at the same or reduced dose.

Serious, including fatal, Pneumocystis jirovecii pneumonia (PJP) occurred in 1% of patients taking COPIKTRA. Provide prophylaxis for PJP during treatment with COPIKTRA and following completion of treatment with COPIKTRA until the absolute CD4+ T cell count is greater than 200 cells/µL. Withhold COPIKTRA in patients with suspected PJP of any grade, and permanently discontinue if PJP is confirmed.

Cytomegalovirus (CMV) reactivation/infection occurred in 1% of patients taking COPIKTRA. Consider prophylactic antivirals during COPIKTRA treatment to prevent CMV infection including CMV reactivation. For clinical CMV infection or viremia, withhold COPIKTRA until infection or viremia resolves. If COPIKTRA is resumed, administer the same or reduced dose and monitor patients for CMV reactivation by PCR or antigen test at least monthly.

Diarrhea or Colitis: Serious, including fatal (1/442; <1%), diarrhea or colitis occurred in 18% of patients receiving COPIKTRA 25 mg BID (N=442). Median time to onset of any grade diarrhea or colitis was 4 months (range: 1 day to 33 months), with 75% of cases occurring by 8 months. The median event duration was 0.5 months (range: 1 day to 29 months; 75th percentile: 1 month).

Advise patients to report any new or worsening diarrhea. For patients presenting with mild or moderate diarrhea (Grade 1-2) (i.e., up to 6 stools per day over baseline) or asymptomatic (Grade 1) colitis, initiate supportive care with antidiarrheal agents, continue COPIKTRA at the current dose, and monitor the patient at least weekly until the event resolves. If the diarrhea is unresponsive to antidiarrheal therapy, withhold COPIKTRA and initiate supportive therapy with enteric acting steroids (e.g., budesonide). Monitor the patient at least weekly. Upon resolution of the diarrhea, consider restarting COPIKTRA at a reduced dose.

For patients presenting with abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, or with severe diarrhea (Grade 3) (i.e., > 6 stools per day over baseline), withhold COPIKTRA and initiate supportive therapy with enteric acting steroids (e.g., budesonide) or systemic steroids. A diagnostic work-up to determine etiology, including colonoscopy, should be performed. Monitor at least weekly. Upon resolution of the diarrhea or colitis, restart COPIKTRA at a reduced dose. For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue COPIKTRA. Discontinue COPIKTRA for life-threatening diarrhea or colitis.

Cutaneous Reactions: Serious, including fatal (2/442; <1%), cutaneous reactions occurred in 5% of patients receiving COPIKTRA 25 mg BID (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 (range: 1 day to 29 months, 75th percentile: 6 months) with a median event duration of 1 month (range: 1 day to 37 months, 75th percentile: 2 months).

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. Review all concomitant medications and discontinue any medications potentially contributing to the event. For patients presenting with mild or moderate (Grade 1-2) cutaneous reactions, continue COPIKTRA at the current dose, initiate supportive care with emollients, antihistamines (for pruritus), or topical steroids, and monitor the patient closely. Withhold COPIKTRA for severe (Grade 3) cutaneous reaction until resolution. Initiate supportive care with steroids (topical or systemic) or antihistamines (for pruritus). Monitor at least weekly until resolved. Upon resolution of the event, restart COPIKTRA at a reduced dose. Discontinue COPIKTRA if severe cutaneous reaction does not improve, worsens, or recurs. For life-threatening cutaneous reactions, discontinue COPIKTRA. In patients with SJS, TEN, or DRESS of any grade, discontinue COPIKTRA.

Pneumonitis: Serious, including fatal (1/442; <1%), pneumonitis without an apparent infectious cause occurred in 5% of patients receiving COPIKTRA 25 mg BID (N=442). Median time to onset of any grade pneumonitis was 4 months (range: 9 days to 27 months), with 75% of cases occurring within 9 months. The median event duration was 1 month, with 75% of cases resolving by 2 months.

Withhold COPIKTRA in patients with new or progressive pulmonary signs and symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on a radiologic exam, or a decline by more than 5% in oxygen saturation, and evaluate for etiology. If the pneumonitis is infectious, patients may be restarted on COPIKTRA at the previous dose once the infection, pulmonary signs and symptoms resolve. For moderate non-infectious pneumonitis (Grade 2), treat with systemic corticosteroids and resume COPIKTRA at a reduced dose upon resolution. If non-infectious pneumonitis recurs or does not respond to steroid therapy, discontinue COPIKTRA. For severe or life-threatening non-infectious pneumonitis, discontinue COPIKTRA and treat with systemic steroids.

Hepatotoxicity: Grade 3 and 4 ALT and/or AST elevation developed in 8% and 2%, respectively, of patients receiving COPIKTRA 25 mg BID (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 (range: 3 days to 26 months), with a median event duration of 1 month (range: 1 day to 16 months).

Monitor hepatic function during treatment with COPIKTRA. For Grade 2 ALT/AST elevation (> 3 to 5 X ULN), maintain COPIKTRA dose and monitor at least weekly until return to < 3 X ULN. For Grade 3 ALT/AST elevation (> 5 to 20 X ULN), withhold COPIKTRA and monitor at least weekly until return to < 3 X ULN. Resume COPIKTRA at the same dose (first occurrence) or at a reduced dose for subsequent occurrences. For grade 4 ALT/AST elevation (> 20 X ULN), discontinue COPIKTRA.

Neutropenia: Grade 3 or 4 neutropenia occurred in 42% of patients receiving COPIKTRA 25 mg BID (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). Withhold COPIKTRA in patients presenting with neutrophil counts < 0.5 Gi/L (Grade 4). Monitor until ANC is > 0.5 Gi/L, then resume COPIKTRA at same dose for the first occurrence or at a reduced dose for subsequent occurrences.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, COPIKTRA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. 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%).

Adverse reactions resulted in treatment discontinuation in 156 patients (35%) most often due to diarrhea or colitis, infection, and rash. COPIKTRA was dose reduced in 104 patients (24%) due to adverse reactions, most often due to diarrhea or colitis and transaminase elevation. 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). COPIKTRA was discontinued in 57 patients (36%), most often due to diarrhea or colitis, infection, and rash. COPIKTRA was dose reduced in 46 patients (29%), most often due to diarrhea or colitis and rash. 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.

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.
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. 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.2,3,4 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. The indication in FL is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 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.5 For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.