On November 14, 2016 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported unaudited financial results for the three months ended September 30, 2016 and reported on corporate developments (Press release, Aptose Biosciences, NOV 14, 2016, View Source;p=RssLanding&cat=news&id=2222358 [SID1234516605]). Unless specified otherwise, all amounts are in Canadian dollars.

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Net loss for the three months ended September 30, 2016 was $4.0 million ($0.31 per share) compared with $3.3 million ($0.27 per share) during the three months ended September 30, 2015. Total cash and cash equivalents at September 30, 2016 were $10.3 million.

"During the third quarter of this year we focused on collecting and delivering to the U.S. Food and Drug Administration (FDA) the manufacturing information required to get our clinical trial of APTO-253 for acute myeloid leukemia (AML) back on track, as returning APTO-253 to the clinic is a major event for the company and for patients with AML," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "Simultaneously, we advanced the development of CG’806, which we believe can be a transformational drug for patients with FLT3-driven AML and for patients with B cell malignancies driven by the Cys481Ser mutant of the BTK enzyme."

Corporate Highlights
During the quarter, Aptose submitted a formal response and data package to the FDA, providing responses to all of the questions cited in the clinical hold letter issued by the FDA. The response to the FDA was based on a prototype drug product that was developed and manufactured to demonstrate the root cause and the corrective actions taken by Aptose to deliver ultimately a drug product that meets FDA standards for the return to the clinic.

As announced in October, the FDA requested that Aptose provide the FDA with the Chemistry, Manufacturing and Control (CMC) package for the actual GMP drug substance and drug product intended to serve as the clinical supply for the trial.

Aptose has now manufactured a batch of APTO-253 drug product that is intended to serve as the clinical supply for the trial, and vials of this new drug product batch have been placed on an accelerated and long-term stability-testing program. Data generated from this drug product batch will comprise much of the CMC package that Aptose will provide to the FDA.

In parallel, Aptose’s clinical team has identified and prepared multiple new clinical sites for the Phase 1b trial of APTO-253. The clinical sites, at major cancer research and treatment centers in the U.S., will be prepared to start the study as soon as the company resumes trial activities and re-initiates dosing and enrollment after the approval by FDA to do so.

Aptose recently announced that new preclinical data for APTO-253 will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting, being held December 3-6, 2016 in San Diego, CA. The poster presentation, Inhibition of c-Myc By Apto-253 As an Innovative Therapeutic Approach to Induce Cell Cycle Arrest and Apoptosis in Acute Myeloid Leukemia, abstract # 1716, can be viewed at the ASH (Free ASH Whitepaper) conference website.

Aptose continued to profile the mechanistic properties and range of action of CG’806. This once daily, oral, first-in-class FLT3/BTK inhibitor demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain), and the molecule is being positioned as a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, suggesting the agent may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.
Financial Results
Net loss for the three months ended September 30, 2016 was $4.0 million ($0.31 per share) compared with $3.3 million ($0.27 per share) in the same period in the prior year. Net loss for the nine months ended September 30, 2016 was $14.7 million ($1.19 per share) compared with $10.2 million ($0.86 per share) during the nine months ended September 30, 2015.
Aptose utilized cash of $3.3 million in operating activities in the three months ended September 30, 2016 compared with $2.6 million during the three months ended September 30, 2015. For the nine months ended September 30, 2016 Aptose utilized cash of $12.4 million compared with $9.0 million in the nine months ended September 30, 2015. The cash utilized in the three months ended September 30, 2016 is higher than the three months ended September 30, 2015 due to a higher net loss as well as cash used to reduce accounts payable and accrual balances in the prior year period. The cash utilized in the nine months ended September 30, 2016 increased compared to the prior year period predominantly due to an increased net loss in the current year period.
Research and Development
Research and development expenses totaled $2.2 million in the three months ended September 30, 2016 compared to $1.7 million during the three months ended September 30, 2015 and totaled $7.8 million for the nine month period ended September 30, 2016 compared with $3.9 million in the same period in the prior year. Research and development costs consist of the following:
Components of research and development expenses:
Three months ended Nine months ended
September 30, September 30,
(in thousands) 2016 2015 2016 2015

Program costs $ 2,081 $ 1,633 $ 6,207 $ 3,750
CrystalGenomics Option Fee − − 1,294 −
Stock-based compensation 71 79 236 145
Depreciation of equipment 12 10 35 19
$ 2,164 $ 1,722 $ 7,772 $ 3,914
The increase in program costs in the three and nine months ended September 30, 2016 compared with the three and nine months ended September 30, 2015 is due to the following reasons:
Costs associated with the LALS/Moffitt collaboration developing epigenetic single molecule inhibitors of multiple targets, including the BET proteins, and other kinases for which no comparable expenses existed in the prior year periods;
Increased research and clinical operations headcount and related costs;
Formulation and manufacturing costs associated with APTO-253 and the root cause analysis of the filter clogging identified in November 2015; and
Increased Contract Research Organization costs related to consultants and advisors as Aptose works towards returning APTO-253 to the clinic.
As of November 2016, Aptose and Laxai Avanti Life Sciences (LALS) have, as part of their drug discovery partnership, generated novel compounds that inhibit both the bromodomain proteins and oncogenic kinases, while improving pharmaceutical properties that could serve as a basis for further optimization towards a lead preclinical candidate. However, due to a prioritization of development efforts, Aptose and LALS have suspended work on the program, and the collaboration with LALS has been terminated. During the hiatus of this program, Aptose and LALS may choose to resume the collaboration in the future.
During the nine months ended September 30, 2016, the Company paid US$1.0 million (CA$1.294 million) for an option fee related to the CG’806 technology. No comparable expense existed in the same period in the prior year.
Stock-based compensation was consistent in the three months ended September 30, 2016 compared with the three months ended September 30, 2015. While the number of option grants in the current year was higher than the prior year, the fair value of those grants was lower in the current year due to a lower stock price.
Stock-based compensation costs allocated to research and development increased in the nine months ended September 30, 2016 to reflect option grants to new employees hired in the second half of 2015 as the expense related to those grants was amortized 50% in the first 12 months.
General and Administrative
General and administrative expenses totaled $1.9 million in the three-month period ended September 30, 2016 compared to $2.2 million in the three months ended September 30, 2015. For the nine month period ended September 30, 2016, general and administrative expenses totaled $6.9 million compared with $7.5 million in the same period in the prior year. General and administrative expenses consist of the following:
Components of general and administrative expenses:
Three months ended Nine months ended
September 30, September 30,
(in thousands) 2016 2015 2016 2015

G&A expenses excluding salaries $ 733 $ 819 $ 2,688 $ 2,997
Salaries 858 838 2,656 2,348
Stock-based compensation 320 572 1,476 2,091
Depreciation of equipment 21 19 63 45
$ 1,932 $ 2,248 $ 6,883 $ 7,481
General and administrative expenses excluding salaries, decreased in the three months ended September 30, 2016 compared with the three months ended September 30, 2015. The decrease is primarily attributable to lower travel, legal and consulting costs associated with projects completed in the prior year offset by higher patent costs in the current year due to new programs acquired in late 2015 and 2016.
General and administrative expenses excluding salaries, decreased in the nine months ended September 30, 2016 compared with the nine months ended September 30, 2015. The decrease is the result of lower travel, consulting and legal costs in the current year related to transactions completed in the prior year as well as lower press release and filing costs associated with a lower cost service provider in the current year periods.
Salary charges in the three months ended September 30, 2016 were consistent with the prior year period as headcount was consistent year over year in the three month period.
Salary charges in the nine months ended September 30, 2016 increased in comparison with the nine months ended September 30, 2015 due to additional headcount in the first half of 2016 compared with the first half of 2015 as well as a higher average CA/US exchange rate which increased the cost of our US denominated salaries in the first six months of 2016 in comparison with the prior year.
Stock-based compensation decreased in the three months ended September 30, 2016 compared with the three months ended September 30, 2015 due to options granted in the current year having a lower valuation and therefore expense compared with options granted in the prior year.
Stock-based compensation decreased in the nine months ended September 30, 2016 compared with the nine months ended September 30, 2015 due to large option grants in April, June and July 2014 which vested 50% during the first year and therefore contribute to higher stock-based compensation expense during the first twelve month period captured in the prior year period.
Finance Expense
Finance expense for the three months ended September 30, 2016 totaled $nil compared with $8 thousand for the three months ended September 30, 2015. For the nine months ended September 30, 2016, finance expense totaled $138 thousand compared with $43 thousand for the same period in the prior year. Finance expense includes the following items:
Three months ended Nine months ended
September 30,
September 30,
(in thousands) 2016 2015 2016 2015
Interest expense $ − $ 8 $ − $ 43
Foreign exchange loss − − 138 −
$ − $ 8 $ 138 $ 43
Interest expense for the three and nine months ended September 30, 2015 relates to interest accrued at a rate of 10% on the remaining balance of convertible promissory notes issued in September 2013 as well as accretion expense related to the conversion feature of the notes. As the promissory notes were converted before September 2015, no interest expense was incurred in 2016.
Foreign exchange loss is the result of the fluctuation of exchange rates between US and Canadian dollars and the impact on our US dollar denominated cash balances.
Finance Income
Finance income totaled $79 thousand in the three months ended September 30, 2016 compared to $717 thousand in the three months ended September 30, 2015. For the nine months ended September 30, 2016, finance income totaled $92 thousand compared with $1.2 million in the same period in the prior year. Finance income includes the following items:
Three months ended Nine months ended
September 30, September 30,
(in thousands) 2016 2015 2016 2015
Interest income $ 12 $ 56 $ 92 $ 232
Foreign exchange gain 67 661 − 1,011
$ 79 $ 717 $ 92 $ 1,243
Interest income represents interest earned on our cash and cash equivalent and investment balances. Foreign exchange gains are the result of an increase in the value of US dollar denominated cash and cash equivalents balances during such periods due to a depreciation of the Canadian dollar compared to the US dollar.
Aptose Biosciences Inc.
Condensed Consolidated Interim Statements of Loss and Comprehensive Loss
(unaudited)
Three Three Nine Nine
months ended months ended months ended months ended
(amounts in 000’s of Canadian Dollars except for per common share data) Sept. 30, 2016 Sept. 30, 2015 Sept. 30, 2016 Sept. 30, 2015
REVENUE $ - $ - $ - $ -
EXPENSES
Research and development 2,164 1,722 7,772 3,914
General and administrative 1,932 2,248 6,883 7,481
Operating expenses 4,096 3,970 14,655 11,395
Finance expense – 8 138 43
Finance income (79 ) (717 ) (92 ) (1,243 )
Net financing (income) expense (79 ) (709 ) 46 (1,200 )
Net loss and comprehensive loss for the period 4,017 3,261 14,701 10,195
Basic and diluted loss per common share $ 0.31 $ 0.27 $ 1.19 $ 0.86
Weighted average number of common shares
outstanding used in the calculation of
basic and diluted loss per common share (000’s) 12,882 11,964 12,390 11,889
The press release, the financial statements and the management’s discussion and analysis for the quarter ended September 30, 2016 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml

On November 14, 2016 MabVax Therapeutics Holdings, Inc. (NASDAQ: MBVX), a clinical stage immuno-oncology drug development company, reported on progress from its two HuMab-5B1 antibody phase I programs evaluating the use of MVT-5873 as a therapeutic antibody and MVT-2163 as an immuno-PET imaging agent in patients with locally advanced and metastatic pancreatic cancer or other CA19-9 positive malignancies.

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MVT-5873 Interim Phase I Data in Pancreatic Cancer
The MVT-5873 phase I clinical trial initiated in February 2016 is designed to establish safety and determine the recommended phase II dose (RP2D) for MVT-5873 as both as monotherapy (Part 1 of the trial), and in combination with standard of care chemotherapy (Part 2) using nab-paclitaxel plus gemcitabine. Initiation of Part 2 requires establishing three safe dose levels for MVT-5873 as monotherapy in patients with relapsed or refractory locally advanced or metastatic pancreatic cancer. The Company reports that the safety of MVT-5873 has been established at three incremental dose levels by treating 16 patients at three clinical sites. While patients continue to be recruited to establish the RP2D, the Company also reports that Part 2 of the clinical trial is now open and will include patients with previously untreated pancreatic cancer receiving a standard of care chemotherapy as defined in the protocol.

To date, the study has consented 28 subjects with 3 in screening, 9 screen failures, and 16 subjects treated. Of the 16 patients treated, six continue to receive treatment. Patients can remain on therapy based on dose tolerability and investigator assessment of continued benefit including assessment of disease status using RECIST 1.1 criteria to evaluate tumor response rate and duration of response. Stable disease was noted for seven patients lasting from three months to eight months. The dosage safety levels established in Part 1 of the trial also support the dosage levels of MVT-5873 to be used in conjunction with the company’s MVT-2163 immuno-PET imaging agent and the MVT-1075 radioimmunotherapy product which is planned to begin phase I clinical evaluation early in 2017.

MVT-2163 Interim Phase I Data in Pancreatic Cancer
The MVT-2163 phase I trial was initiated in June of this year to evaluate the company’s next generation diagnostic PET imaging agent in patients with locally advanced or metastatic adenocarcinoma of the pancreas (PDAC) or other CA19-9 positive malignancies. MVT-2163 (89Zr-HuMab-5B1) combines the well-established PET imaging radiolabel Zirconium [89Zr] with the targeting specificity of MVT-5873. This trial is designed to establish safety, pharmacokinetics, biodistribution, and the amount of MVT-5873 to be used in co-administration to obtain optimized PET scan images. The company has demonstrated interim safety, pharmacokinetics, and biodistribution by completing the initial two cohorts of patients: the first cohort administered MVT-2163 alone and the second cohort administered MVT-2163 following a blocking dose of MVT-5873. The company reports that the initial PET images demonstrated target specificity by correlation with lesions identified by conventional computerized tomography (CT) scans. The biodistribution data obtained in the first two cohorts demonstrates improvement in PET images by pre-administration of MVT-5873, as has been observed with other antibody based PET agents. The company is actively recruiting patients and expects to establish the optimal co-administration dose of MVT-5873 early in 2017.

"Our strategy at the outset was to initiate these two clinical trials concurrently to address the key questions of safety and targeting specificity for the HuMab-5B1 antibody. We are highly encouraged by these promising early results from the MVT-5873 and MVT-2163 clinical trials," stated President and CEO J. David Hansen. He added, "We are moving ahead with the planned combination of MVT-5873 with a standard of care chemotherapy in a chemotherapy-naïve pancreatic cancer patient population and are looking forward to presenting these results next year. We are continuing to accrue patients in order to establish the RP2D for MVT-5873 as a monotherapy. In the MVT-2163 trial, dose escalation continues to confirm optimal dose and timing for the best PET scan image. Finally, the company remains on track for submitting the Investigational New Drug Application (IND) for MVT-1075 to the Food And Drug Administration (FDA) later this year, and plans to initiate the phase I trial of MVT-1075 in the first half of 2017 after receiving FDA authorization to proceed."

On November 14, 2016 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a biopharmaceutical company dedicated to innovative therapeutics addressing cancer and other unmet medical needs, reported financial results for the three and nine months ended September 30, 2016

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CASI PHARMACEUTICALS REPORTS THIRD QUARTER 2016 FINANCIAL RESULTS.

As of September 30, 2016, CASI had cash and cash equivalents of approximately $24.1 million.

CASI reported a net loss for the third quarter of 2016 of ($1.7 million), or ($0.03) per share. This compares with a net loss of ($1.6 million), or ($0.05) per share, for the same period last year. For the first nine months of 2016, the reported net loss was ($6.8 million), or ($0.15) per share as compared to ($5.5 million), or ($0.17) per share for the first nine months of 2015.

Commenting on these results, Sara B. Capitelli, CASI’s Vice President, Finance, said, "Our third quarter 2016 financial results were in line with expectations. Research and development expenses increased during the 2016 period compared with the previous year primarily due to costs associated with our ENMD-2076 fibrolamellar carcinoma trial which began in late 2015. As we continue to execute our regulatory, clinical and business development plan, we expect operating expenses to increase for the remainder of 2016."

Ken K. Ren, Ph.D., CASI’s Chief Executive Officer, stated, "I am pleased with our third quarter financial results. In October, we completed the last closing ($7.8 million) of our previously announced financing, and also completed an additional $3.0 million financing. Participants in the financing included our existing shareholders represented on our Board of Directors. In addition to a positive financial outlook, we look forward to further advancing our proprietary clinical candidate ENMD-2076, as well as MARQIBO, ZEVALIN and EVOMELA in China, and securing additional in-license assets to expand our pipeline. Proceeds from the recent financings will help accelerate these activities."

On November 14, 2016 Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), a biopharmaceutical company developing oral therapies that target the various phases of cell cycle control for the treatment of cancer and other serious disorders, reported financial results and business highlights for the third quarter ended September 30, 2016 (Press release, Cyclacel, NOV 14, 2016, View Source [SID1234516611]).

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The Company’s net loss applicable to common shareholders for the third quarter ended September 30, 2016 was $3.0 million, or $0.86 per basic and diluted share, compared to net loss applicable to common shareholders of $2.8 million, or $0.95 per basic and diluted share for the third quarter ended September 30, 2015. As of September 30, 2016, cash and cash equivalents totaled $18.0 million.

"SEAMLESS, a Phase 3 study of oral sapacitabine capsules, represents one of the largest clinical trials conducted in elderly patients with AML who are unfit for or refused intensive chemotherapy. Following completion of follow-up at the beginning of the quarter, we have been conducting data validation operations," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "We are pleased to report that this process is nearing completion following which the database will be locked and transferred to our statistical analysis vendor. We anticipate reporting top line results late in the fourth quarter of 2016 or in early 2017."

"The collection and processing of SEAMLESS Phase 3 data represent many years of effort in our search to offer a new treatment regimen for this older patient population. We will soon analyze the data and determine whether the results warrant regulatory submissions," said Dr. Judy Chiao, VP, Clinical Development and Regulatory Affairs. "We are grateful to the patients, their families, the investigators and their teams for their valuable contributions to this study."

"During the quarter data presented at a pediatric cancer meeting demonstrated that CYC065, our second generation Cyclin Dependent Kinase (CDK) inhibitor, prolonged survival in MYCN-addicted neuroblastoma models. The data further validate the mechanism of CYC065 and provide a rationale for clinical investigation in neuroblastoma with MYCN amplification, a major oncogenic driver of this childhood cancer. MYC family proteins are important therapeutic targets in other oncology indications, including certain solid tumors, leukemias and lymphomas. Early clinical and preclinical data from our DNA damage response program suggest that our transcriptional CDK inhibitors may have a synergistic effect with other anticancer agents, including sapacitabine. We look forward to reporting new data from our ongoing clinical studies of sapacitabine and seliciclib in BRCA positive patients and of CYC065 in patients with solid tumors," continued Mr. Rombotis.

BUSINESS HIGHLIGHTS

SEAMLESS study

Phase 3 study of oral sapacitabine capsules alternating with intravenous decitabine compared to decitabine alone, as first-line treatment in patients aged 70 years or older with AML who are unfit for or refused intensive chemotherapy; cleaned and validated dataset being finalized and database lock imminent.
DNA damage response program

The Phase 1 combination of sapacitabine and seliciclib is continuing enrollment in an extension study in an enriched population of BRCA positive patients with advanced breast cancer.
Cyclin dependent kinase (CDK) inhibitor program

Continued recruitment in Phase 1, first-in-human trial of CYC065, a CDK2/9 inhibitor, to evaluate safety, tolerability and pharmacokinetics in patients with solid tumors. The sixth dose escalation level has been reached.

Preclinical data presented at the Childhood Cancer Meeting 2016 demonstrated effectiveness of CYC065 against neuroblastoma models with an overexpression and amplification of MYCN, a driver of neuroblastoma.
KEY UPCOMING MILESTONES

SEAMLESS study

Report top-line data and determination of submissibility to regulatory authorities, anticipated late fourth quarter 2016 or early 2017.
Progress the Paediatric Investigation Plan for sapacitabine with the European Medicines Agency.
DNA damage response program

Progress Phase 1 sapacitabine and seliciclib extension cohort in a breast cancer patient population enriched for BRCA mutations.
Initiate Phase 1 part 3, to include BRCA mutation positive, pancreatic and ovarian cancer patients.
CDK Inhibitor Program

Report top-line results of the CYC065 Phase 1 trial in patients with solid tumors.
Report data when available from ongoing investigator sponsored trials (ISTs) evaluating seliciclib in patients with Cushing’s disease and rheumatoid arthritis. Additionally, seliciclib is being evaluated in cystic fibrosis though a license and supply agreement with ManRos Therapeutics.
Sapacitabine in myelodysplastic syndromes (MDS)

Plan Phase 1/2 trial of sapacitabine in combination with other agents to determine safety and tolerability.
Plan a Phase 2 randomized controlled trial (RCT) of sapacitabine in combination with other agents following review of all relevant clinical data with mature follow-up.
THIRD QUARTER 2016 FINANCIAL RESULTS

Cash and cash equivalents totaled $18.0 million as of September 30, 2016 compared to $20.4 million at December 31, 2015. Approximately $5.2 million was raised from the sale of common stock through the Company’s at-the-market facility with FBR Capital Markets. A further $1.5 million was received in October 2016 through this facility, resulting in a proforma cash balance as of September 30, 2016 of $19.5 million. Based on current plans, the Company estimates that it has capital resources to fund operations through the second quarter of 2018.

Revenue for the three months ended September 30, 2016 was $0.2 million, compared to $0.7 million for the same period of the previous year, with the decrease primarily related to grant revenue related to CYC065, for which the grant ended in December 2015.

Research and development expenses were $2.4 million for the three months ended September 30, 2016 and $2.9 million for the three months ended September 30, 2015.

General and administrative expenses were $1.3 million for the three months ended September 30, 2016 and $1.2 million for the three months ended September 30, 2015.

On November 12, 2016 Bristol-Myers Squibb Company (NYSE:BMY) and Innate Pharma SA (Euronext Paris: FR0010331421 – IPH) reported an interim efficacy analysis from a Phase 1/2 study of the combination of lirilumab and Opdivo (nivolumab) in the cohort of advanced platinum refractory squamous cell carcinoma of the head and neck (SCCHN), including exploratory biomarker analyses of patient response by level of PD-L1 expression (Press release, Bristol-Myers Squibb, NOV 12, 2016, View Source [SID1234516510]). Among 29 evaluable patients with SCCHN, the objective response rate (ORR), a secondary endpoint measured by Response Evaluation Criteria In Solid Tumors (RECIST), was 24% (n=7). Seventeen percent (n=5) of these evaluable patients had deep responses, with reductions in tumor burden greater than 80%. Early signals of enhanced clinical benefit were observed in PD-L1 positive tumors, with an ORR of 41% (7/17) in patients with ≥1% PD-L1 expression.

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Lirilumab is directed against the inhibitory killer-cell immunoglobulin-like receptors (KIRs) expressed predominantly on natural killer (NK) cells, which belong to the innate immune system, while Opdivo blocks the inhibitory function of the PD-1 receptor on T cells. These data mark the first report of potential efficacy with an anti-KIR antibody in combination with an anti-PD-1 therapy, and were presented at a late-breaking oral presentation (abstract 456) at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31 Annual Meeting on November 12 at 11:15 a.m. EST in National Harbor, Maryland. Preliminary efficacy and exploratory biomarker analyses of patient response by biomarker subgroups were presented.

The safety profile associated with lirilumab in combination with Opdivo was generally consistent with that observed with Opdivo monotherapy. The overall rate of treatment-related adverse events (TRAEs) was reported as 72% (114/159) and the rate of Grade 3-4 TRAEs was 15% (24/159). Discontinuations due to TRAEs occurred in 8% of patients (12/159). These safety data were also reported at the 2016 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

"The interim efficacy results indicate that targeting both the KIR and PD-1 pathways with lirilumab and Opdivo, respectively, may provide enhanced clinical activity, particularly in PD-L1 positive tumors, with deep and durable responses in some patients," said Rom Leidner, Medical Oncologist, Earle A. Chiles Research Institute, Providence Cancer Center, and lead author of the study. "We look forward to continuing the study of this novel combination in patients with advanced platinum refractory squamous cell carcinoma of the head and neck, which is the seventh-leading cause of cancer globally."

"The preliminary signals of anti-tumor activity we are seeing with the combination of lirilumab and Opdivo in head and neck cancer patients compare favorably to data previously presented on Opdivo monotherapy in a similar patient population. We are encouraged by the suggestion of enhanced benefit, particularly in inflamed tumors as defined by increasing PD-L1 expression," said Tim Reilly, head of Oncology Early Assets Development at Bristol-Myers Squibb. "We aim to apply what we have been learning about these complementary mechanisms and biomarker subgroups to maximize the potential clinical benefit of lirilumab and Opdivo across a range of tumor types and are excited about continuing to expand our study of Opdivo with complementary pathways."

"We are very encouraged by these interim efficacy data and are eagerly awaiting the next steps of the clinical development of the combination of lirilumab and Opdivo" said Pierre Dodion, Chief Medical Officer of Innate Pharma. "These clinical data constitute crucial progress that validates our pioneering work on the role of innate immunity and NK cells in cancer. They support our ambition to be at the forefront of developing novel combination immunotherapies."

About CA223-001: A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-KIR (Lirilumab) Administered in Combination With Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors

CA223-001 is a Phase 1/2 dose escalation and cohort expansion study of lirilumab in combination with nivolumab in 159 patients with advanced solid tumors. In this trial, patients received lirilumab (0.1, 0.3, 1.0, or 3.0 mg/kg) once every 4 weeks and nivolumab (3 mg/kg) once every 2 weeks.

During dose escalation, patients with advanced solid tumors who progressed after ≥ 1 prior therapy received lirilumab 0.1–3.0 mg/kg once every 4 weeks (Q4W) plus nivolumab 3.0 mg/kg Q2W. Cohort expansion was initiated at the maximum dose of lirilumab 3.0 mg/kg Q4W plus nivolumab 3.0 mg/kg Q2W in patients with advanced solid tumors. The data reported at SITC (Free SITC Whitepaper) pertain to an expansion cohort in SCCHN. Key study endpoints include safety (primary), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and biomarker assessments.

The purpose of this Phase 1/2 open label study is to determine the safety of the combination of lirilumab and nivolumab and to explore the preliminary anti-tumor activity of the combination in patients with a range of advanced solid tumors.

About Lirilumab (IPH2102/BMS-986015):

Lirilumab is a fully human monoclonal antibody that is designed to act as a checkpoint inhibitor by blocking the interaction between KIR2DL-1,-2,-3 inhibitory receptors and their ligands. Blocking these receptors facilitates activation of NK cells and potentially some subsets of T cells, ultimately leading to destruction of tumor cells.

Lirilumab is licensed to Bristol-Myers Squibb Company. As part of the agreement with Innate Pharma, Bristol-Myers Squibb holds exclusive worldwide rights to develop, manufacture and commercialize lirilumab and related compounds blocking KIR receptors, for all indications. Under the agreement, Innate Pharma conducts the development of lirilumab through Phase 2 in acute myeloid leukemia ("AML").

Innate Pharma is currently testing lirilumab in a randomized, double-blind, placebo-controlled Phase 2 trial as maintenance treatment in elderly patients with AML in first complete remission ("EffiKIR" trial). In addition, lirilumab is also being evaluated by Bristol-Myers Squibb in clinical trials in combination with other agents in a variety of tumor types.

About Head & Neck Cancer

Cancers that are known as head and neck cancers usually begin in the squamous cells that line the moist mucosal surfaces inside the head and neck, such as inside the mouth, the nose and the throat. Head and neck cancer is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per year. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease. Squamous cell carcinoma of the head and neck (SCCHN) accounts for approximately 90% of all head and neck cancers with global incidence expected to increase by 17% between 2012 and 2022. Risk factors for SCCHN include tobacco and alcohol consumption. The Human Papilloma Virus (HPV) infection is also a risk factor leading to rapid increase in oropharyngeal SCCHN in Europe and North America. Quality of life is often impacted for SCCHN patients, as physiological function (breathing, swallowing, eating, drinking), personal characteristics (appearance, speaking, voice), sensory function (taste, smell, hearing), and psychological/social function can be affected.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 57 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 47 countries, including the United States and the European Union.

U.S. FDA APPROVED INDICATIONS FOR OPDIVO

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication 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.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.

Complications of Allogeneic HSCT after OPDIVO

Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.

Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Embryo-Fetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population [n=95]). In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infections, and sepsis.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population [n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator’s choice.

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Checkmate Trials and Patient Populations

Checkmate 067 – advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 – advanced melanoma; Checkmate 017 – squamous non-small cell lung cancer (NSCLC); Checkmate 057 – non-squamous NSCLC; Checkmate 025 – renal cell carcinoma; Checkmate 205/039 – classical Hodgkin lymphoma; Checkmate 141 – squamous cell carcinoma of the head and neck.

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.