On December 6, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that updated findings from the phase 1b KEYNOTE-028 study investigating the use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in previously treated patients with advanced small cell lung cancer (SCLC) and malignant pleural mesothelioma, showed clinical activity and durable responses in some patients (Press release, Merck & Co, DEC 6, 2016, View Source [SID1234516954]). These data were featured in oral presentations at the 17th World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer.

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"As data from our initial trials exploring KEYTRUDA mature, we are encouraged to see durable clinical activity in difficult-to-treat cancers such as small cell lung cancer and malignant pleural mesothelioma, where new treatments are clearly needed," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "With our extensive immuno-oncology research program, we are developing KEYTRUDA across a range of thoracic malignancies, and we have additional studies underway in these two cancer types."

KEYNOTE-028 is an ongoing multi-cohort, non-randomized Phase 1b basket trial evaluating the safety, tolerability, and anti-tumor activity of KEYTRUDA monotherapy (10 mg/kg dosed every two weeks) in more than 450 patients with PD-L1 positive tumors across 20 different types of cancer. PD-L1 positivity was defined as expression in one percent or more of tumor and associated inflammatory cells or positive staining in stroma. The primary outcome measure is overall response rate (ORR), with secondary outcome measures of progression-free survival (PFS), overall survival (OS), and duration of response.

The KEYTRUDA (pembrolizumab) clinical development program includes more than 30 tumor types in nearly 400 clinical trials, including more than 200 trials that combine KEYTRUDA with other cancer treatments. Merck has initiated a phase 2 trial, KEYNOTE-158, to further evaluate KEYTRUDA in advanced solid tumors including SCLC and malignant pleural mesothelioma.

Results from KEYNOTE-028 SCLC Cohort (Abstract #OA05.01)

Data from the SCLC cohort of the KEYNOTE-028 trial were presented in an oral presentation on Dec. 5 by Dr. Patrick Ott, Dana-Farber Cancer Institute.

Updated findings from 24 heavily pre-treated patients with advanced SCLC demonstrated a confirmed ORR of 33.3 percent (n=8/24) (95% CI, 15.6%-55.3%), including one complete response and seven partial responses. One patient had stable disease and 13 patients had progressive disease. Responses were durable, with a median duration of response of 19.4 months (95% CI, range: 3.6+ to 20.0+).

Additionally, the median PFS was 1.9 months (95% CI, 1.7-5.9), with a six-month PFS rate of 28.6 percent and 12-month PFS rate of 23.8 percent. The median OS was 9.7 months (95% CI, 4.1-NR), with a six-month OS rate of 66.0 percent and a 12-month OS rate of 37.7 percent.

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade 3-5 treatment-related adverse events were asthenia, blood bilirubin increased, colitis and intestinal ischemia (n=1 for all). Some patients experienced adverse events of special interest, including autoimmune thyroiditis, infusion site reaction, cytokine release syndrome and colitis (n=1 for all).

"These long-term data, which show meaningful response rates and durable responses in certain patients with small cell lung cancer, are encouraging," said Dr. Ott. "With these findings, we are advancing understanding of the potential for immunotherapy to make a difference for these patients."

Results from KEYNOTE-028 Malignant Pleural Mesothelioma Cohort (Abstract #OA13.03)

Data from the malignant pleural mesothelioma cohort of the KEYNOTE-028 trial were presented in an oral presentation on Dec. 6 by Dr. Evan Alley, Abramson Cancer Center, University of Pennsylvania.

Results showed a confirmed ORR of 20.0 percent (n=5/25) (95% CI, 6.8-40.7). All responses were partial responses and 13 patients had stable disease. The median duration of response was 12.0 months (range, 3.7-20.5+). In total, 60.9 percent of evaluable patients experienced a decrease in tumor size.

Additionally, the median PFS was 5.4 months (95% CI, 3.4-7.5), with a six-month PFS rate of 45.8 percent and a 12-month PFS rate of 20.8 percent. Median OS was 18.0 months (95% CI, 9.4-NR), with a six-month OS rate of 83.5 percent and a 12-month OS rate of 62.6 percent.

The safety profile of KEYTRUDA (pembrolizumab) was consistent with that observed in previously reported studies. Grade 3 treatment-related adverse events were ALT increase, appetite decrease, dyspnea, iridocyclitis, neutrophil count decreased, pyrexia and thrombocytopenia (n=1 for all). Some patients experienced adverse events of special interest, including erythema/erythema multiforme, hypothyroidism, infusion-related reaction, iridocyclitis and rhabdomyolysis (n=1 for all). There were no Grade 4 or 5 treatment-related adverse events and no treatment-related deaths.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA (pembrolizumab) is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA (pembrolizumab) can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA (pembrolizumab) and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA (pembrolizumab) occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes nearly 400 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On December 6, 2016 Oncolytics Biotech Inc. ("Oncolytics" or the "Company") (TSX:ONC) (OTCQX:ONCYF) reported that Dr. Kevin Kelly and colleagues made a poster presentation at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting (Filing, 6-K, Oncolytics Biotech, DEC 6, 2016, View Source [SID1234516972]). The poster presentation, titled "Oncolytic Reovirus Immune Priming: A Phase Ib Study of REOLYSIN with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma," provides initial findings from the Company’s REO 019 Phase Ib trial. The ASH (Free ASH Whitepaper) Annual Meeting runs from December 3rd to 6th in San Diego, CA.

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The study is a two-stage open-label Phase Ib trial of adult patients with relapsed or refractory multiple myeloma following at least one line of therapy. This study was designed to evaluate tolerability, to confirm that the addition of REOLYSIN to bortezomib increases endoplasmic reticulum stress and death of myeloma cells (as shown in preclinical models) and to document pharmacodynamic effects as part of the characterization of the mechanism(s) of action of REOLYSIN in multiple myeloma. Kevin Kelly, M.D., Ph.D. of the Keck School of Medicine of the University of Southern California (USC), is the principal investigator.

"The combination of REOLYSIN, bortezomib and dexamethasone was well-tolerated in these heavily pre-treated patients, even in those who had been previously exposed to bortezomib," said Dr. Kevin Kelly. "Preliminary evidence of activity of this combination was documented. It was also shown that the combination therapy induced the apoptosis of myeloma cells and stimulated the immune system, highlighted by improved cytotoxic T cell infiltration and activation of checkpoint inhibitors (IDO, PD-L1) in the tumor."

The dose escalation study tested three doses ranging from 3 to 9×1010 TCID50 on days 1, 2, 8, 9, 15 and 16, with 40 mg dexamethasone and 1.5 mg/m2 bortezomib on days 1, 8, and 15. Cycles were repeated every 28 days. A maximum tolerated dose was not defined because there were no dose-limiting toxicities in the first two cohorts. Cohort 3 is still enrolling patients. The combination was well tolerated and most treatment emergent toxicities were transient and easily managed with supportive care. The most common treatment related toxicities were grade 1 diarrhea, grade 1 fatigue, grade 1 flu-like symptoms and grade 1 headache.

Three patients completed 1 cycle of treatment only, 2 completed 3 cycles, 1 completed 4 cycles and 1 completed 7 cycles. Two patients remain on protocol (1 has completed 3 cycles (Cohort 3) and the other 7 cycles (Cohort 2)). Six patients were evaluable for response, 4 patients had stable disease lasting at least 1 cycle, whereas 3 patients had progressive disease at the end of cycle 1.

"It is intriguing that this combination therapy with REOLYSIN induced an immune response with mainly grade 1 level toxicity, which is consistent with what we have observed in studies with other REOLYSIN combinations in solid tumors," said Dr. Matt Coffey, Interim President and CEO of Oncolytics Biotech. "These data build on what we have observed in previous studies in both multiple myeloma and solid tumours, and further investigation is needed to evaluate if the immune modulatory and anti-tumor activity of REOLYSIN can provide a therapeutic opportunity to patients with hematological malignancies when combined with other targeted treatments including immunotherapies."

A copy of the poster will be available on the Oncolytics website at: View Source

About Multiple Myeloma
Multiple Myeloma is a cancer of the plasma cells and the second most common hematological malignancy. The American Cancer Society estimates there will be 30,330 new cases diagnosed in the United States and 12,650 deaths from the disease in 2016.

On December 6, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that clinical data from its lead product candidate CB-839, a first-in-class glutaminase inhibitor, will be presented at the 2016 San Antonio Breast Cancer Symposium, December 6-10, 2016 in San Antonio, Texas (Press release, Calithera Biosciences, DEC 6, 2016, View Source;p=RssLanding&cat=news&id=2227919 [SID1234516955]). The data demonstrate the clinical activity, tolerability and unique mechanism of action of CB-839 in patients with advanced/metastatic triple negative breast cancer (TNBC).

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"Triple negative breast cancer in the advanced and metastatic population remains a significant unmet need. We are particularly pleased to observe responses with CB-839 plus paclitaxel in taxane-refractory patients," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

Dr. Angela DeMichele from the University of Pennsylvania will present in a poster session, "Phase I study of CB-839, a small molecule inhibitor of glutaminase, in combination with paclitaxel in patients with triple negative breast cancer," (Abstract P6-11-05). The abstract was selected for presentation on Saturday, December 10, 2016. Eligible patients must have locally advanced/metastatic TNBC, with prior paclitaxel treatment allowed. As of November 25, 2016, 28 triple negative breast cancer patients had been treated with doses of CB-839 of 400, 600 or 800 mg bid in combination with 80 mg/m2 IV paclitaxel, weekly, three weeks out of four; 23 were evaluable for response. The majority of patients had received at least three prior lines of therapy, with 43% of patients treated with five or more prior therapies in the advanced/metastatic setting. Most patients had received prior taxane therapy in either the neo-adjuvant or metastatic setting. Among evaluable patients treated with CB-839 doses of at least 600 mg bid (n=16), there are 5 partial responses (31%) and disease control (response or stable disease) in 11 patients (69%). In addition, the combination overcomes resistance to paclitaxel in heavily pretreated TNBC patients. There is a 38% response rate and 50% disease control rate in patients who received prior taxanes in the metastatic setting. There is a 50% response rate among taxane-refractory African American patients, consistent with higher glutamine utilization observed in tumors from this population.1

The combination of CB-839 and paclitaxel has been well tolerated to date, with adverse events that have been easily manageable and reversible, including several paclitaxel related toxicities. There was one case of dose-limiting, recurrent grade 3 neutropenia at the 400 mg dose level, which led to a reduction in the dose of paclitaxel for that patient. The most frequent adverse event ≥ Grade 3 is neutropenia (n=6).

On December 6, 2016 TG Therapeutics, Inc. (NASDAQ:TGTX), reported the presentation yesterday of data from three combination studies involving the Company’s lead compounds, TGR-1202, the Company’s once-daily PI3K delta inhibitor, and TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, in San Diego, California (Press release, TG Therapeutics, DEC 6, 2016, View Source [SID1234516973]).

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Michael S. Weiss, the Company’s Executive Chairman and Interim CEO stated, "We are very pleased to continue to see a highly differentiated safety profile for TGR-1202 across multiple double and triple combination studies with a high level of activity. Each of the four clinical studies presented at the ASH (Free ASH Whitepaper) meeting, enhanced our overall understanding of the breadth of activity of TGR-1202. In addition to DLBCL, FL and CLL, where we have already shown data previously, it was nice to see the flexibility of TGR-1202 and its ability to be combined with brentuximab vedotin in relapsed or refractory Hodgkin’s and with ruxolitinib in Myelofibrosis." Mr. Weiss continued, "We are also encouraged by the triple combination data of TG-1101, TGR-1202, and bendamustine in relapsed or refractory, difficult to treat, DLBCL and FL patients which showed no discontinuations for a treatment related adverse event, as well as an 80% overall response rate across both DLBCL and FL patients and a high level of CR’s. We, and our investigators, believe this triplet combination is a promising regimen and plan to study it in this patient population in a registration-directed trial."

Highlights from yesterday’s presentations include the following:

Poster Presentation: Combination of Ublituximab, TGR-1202, and Bendamustine Demonstrates Significant Activity in Patients with Advanced DLBCL and Follicular Lymphoma (Abstract Number 4197)

This poster presentation includes data from patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL) treated with the triple combination of TG-1101 (ublituximab), TGR-1202 and bendamustine. Nineteen patients were evaluable for safety of which 15 were evaluable for efficacy (3 patients were too early to evaluate and 1 patient had a non-related adverse event (AE) prior to efficacy assessment). The triple combination appears well tolerated with no discontinuations for a treatment related AE. Neutropenia and anemia were the only Grade 3/4 AE’s occurring in more than 1 patient. Importantly, no Grade 3/4 transaminitis was reported, no events of pneumonia or pneumonitis, and only 1 transient event of Grade 3 diarrhea, with a duration of 1 day, was observed. Eleven patients (58%) were refractory to prior treatment. Median time on study at the data cut off was approximately 6 months with the majority of patients continuing on study and follow-up ongoing.

Efficacy highlights from this poster include:

71% (5 of 7) Overall Response Rate (ORR), including a 43% Complete Response (CR) rate observed in patients with relapsed or refractory DLBCL
88% (7 of 8) ORR, including a 37% CR rate observed in patients with relapsed or refractory FL 4/6 CR’s that were achieved between the DLBCL and FL groups occurred at the first 8 week efficacy assessment
First response assessment occurred at Month 3 following initiation of therapy, with durable responses observed notably amongst DLBCL patients.
Poster Presentation: A Phase I Trial of TGR-1202, a Next Generation Once-Daily PI3Kδ Inhibitor, in Combination with Brentuximab Vedotin, in Patients with Relapsed/Refractory Hodgkins Lymphoma (Abstract Number 4146)

This poster presentation includes data from patients with relapsed and refractory Hodgkin’s Lymphoma (HL) treated with TGR-1202 at either 400mg or 600mg dosed orally once daily in combination with brentuximab vedotin in continuous 21 day cycles. 14 patients were evaluable for safety, of which 11 were evaluable for efficacy (3 discontinued prior to disease evaluation (2 AE’s and 1 withdrew consent)). 43% (6 of 14) of patients had prior exposure to brentuximab vedotin and all were refractory to prior brentuximab vedotin therapy. The combination demonstrated tolerability with nausea, diarrhea, and neutropenia being the most prevalent adverse events. Notably all but one case of diarrhea was Grade 1 or 2 in severity.

Efficacy highlights from this poster include:

60% (3 of 5) ORR, including a 40% CR rate observed across brentuximab vedotin refractory patients
64% (7 of 11) ORR, including a 45% CR rate observed across all patients treated

Oral Presentation: Preliminary Results from a Phase I Dose Escalation Trial of Ruxolitinib and the PI3Kδ Inhibitor TGR-1202 in Myelofibrosis (Abstract Number 1125)
This oral presentation includes data from patients with myelofibrosis treated with the combination of ruxolitinib, the JAK1/2 inhibitor and TGR-1202. The combination was well tolerated and efficacious in the twelve patients treated. The most prevalent adverse events deemed at least possibly related to TGR-1202 included anemia, thrombocytopenia, neutropenia, AST/ALT elevation and amylase/lipase elevation and diarrhea, all of which were notably Grade 1/2 with the exception of Grade 3 amylase/lipase elevation seen in 2 patients (16.7%), and Grade 3 diarrhea seen in 1 patient (8.3%). Presentation highlights included:

The patient population enrolled was advanced, with the majority having 2 or more prior mutations at baseline;
Per protocol, all enrolled patients were on a stable dose of ruxolitinib monotherapy with best response to ruxolitinib monotherapy achieved prior to enrollment;
Following the addition of TGR-1202, 11/12 patients experienced improvement in hemoglobin, many with a concomitant reduction in platelet counts indicating clinical benefit beyond ruxolitinib monotherapy; and
83% of study participants experienced clinical benefit (hematologic improvement, reduced spleen size and/or improvement in symptoms) including one patient who achieved a CR and continues on study, now out 72 weeks

PRESENTATION DETAILS:
Copies of the above referenced presentations are available on the Company’s website at www.tgtherapeutics.com, located on the Publications page.

TG THERAPEUTICS INVESTOR & ANALYST EVENT:
TG Therapeutics held an investor and analyst reception yesterday, at the Marriott Gaslamp, in San Diego, California. The audio file and slide presentation are available for review on the Events page, located within the Investors & Media section of the Company’s website at www.tgtherapeutics.com.

On December 6, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported results from the ZUMA-1 trial of axicabtagene ciloleucel (KTE-C19) in patients with chemorefractory aggressive non-Hodgkin lymphoma (NHL) in two oral presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) 58th Annual Meeting in San Diego, California (Press release, Kite Pharma, DEC 6, 2016, View Source [SID1234516957]).

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ZUMA-1 enrolled 111 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL). Patients were required to have chemorefractory disease, defined as progressive or stable disease as best response to last line of therapy, or disease progression ≤12 months after autologous stem cell transplant. Manufacturing was successful for 110 patients, and 101 patients were treated. The pre-specified interim analysis was triggered when 51 patients with DLBCL had a minimum of three months of follow-up. At the time of interim analysis, 11 patients with PMBCL/TFL had been followed for three months. An additional 31 patients with one month of follow-up were included in the late breaker presentation.

"The vast majority of patients enrolled in ZUMA-1 are unable to undergo autologous stem cell transplant due to chemorefractory disease. This group has a dire need for more effective therapies," said Jeff Wiezorek, M.D., Senior Vice President of Clinical Development. "We are encouraged by the high rate of complete remissions in this group and look forward to presenting longer follow-up at the primary analysis in the first quarter 2017. We are grateful to the patients and investigators who have made this important study possible."

ZUMA-1 met the primary endpoint of objective response rate (ORR), p < 0.0001. Response rates by disease subtype are shown in the table below. Responses were observed across key subgroups, including 75 percent CR in patients who relapsed in ≤12 months after autologous stem cell transplant and 47 percent CR in patients refractory to second line or later chemotherapy. At the month three assessment, 39 percent of patients were in CR.

Best Overall Response in Patients with ≥3 Month Follow-up
Subgroup
N ORR CR
DLBCL
51 76% 47%
TFL / PMBCL 11 91% 73%
Total 62 79% 52%
In 93 patients with a minimum one month follow-up, the most common grade 3 or higher adverse events included neutropenia (63 percent), anemia (42 percent), leukopenia (40 percent), febrile neutropenia (29 percent), thrombocytopenia (26 percent), encephalopathy (19 percent), hypophosphatemia (17 percent), and decreased lymphocyte count (17 percent). Grade 3 or higher CRS and NE were observed in 13 percent and 29 percent of patients, respectively. Three patients died from treatment-emergent adverse events (hemophagocytic lymphohistiocytosis, cardiac arrest in the setting of CRS and pulmonary embolism). There were no cases of cerebral edema.

The primary analysis of ZUMA-1 will include a minimum of 6 months of follow-up. Kite intends to seek regulatory approval of axicabtagene ciloleucel in refractory aggressive NHL and plans to complete its rolling submission of the Biologics License Application (BLA) in the first quarter of 2017.

The late-breaker abstract (LBA-6), "KTE-C19 (anti-CD19 CAR T Cells) Induces Complete Remissions in Patients with Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Results from the Pivotal Phase 2 ZUMA-1," was presented by Sattva S. Neelapu, M.D., Associate Professor, Deputy Department Chair ad interim, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. View Source

About axicabtagene ciloleucel

Kite Pharma’s lead product candidate, axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.