On May 5, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX) reported its financial results for the first quarter ended March 31, 2017 and recent company developments (Press release, TG Therapeutics, MAY 5, 2017, View Source [SID1234518881]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "2017 has been an exciting and busy year for us already, with both the announcement of the positive topline data from the Phase 3 GENUINE trial and the subsequent $89M capital raise. Having achieved these two important milestones, we believe the company is well positioned for a successful remainder of the year and beyond." Mr. Weiss continued, "We plan to focus our attention on advancing our clinical programs towards success and look forward to a data and news rich summer where we will be presenting a more detailed analysis of the GENUINE data, announcing the interim analysis data from both our UNITY-CLL Phase 3 trial and UNITY-DLBCL trial, as well as commencing our global Phase 3 program in MS."

Recent Developments and Highlights

Received orphan drug designation for the combination of TG-1101 and TGR-1202 for the treatment of CLL and DLBCL
Announced the publication of clinical data from the Phase 1/2 trial of TG-1101 monotherapy in the British Journal of Haematology
Announced positive topline data from Phase 3 GENUINE study of TG-1101 in combination with ibrutinib in patients with high risk CLL
Solidified the Company’s balance sheet raising approximately $89M in gross proceeds through the combination of a public offering and an at-the-market sales facility
Presented preclinical data on our anti-PD-L1 monoclonal antibody at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting
Presented preliminary results, including B-cell depletion data from ongoing Phase 2 study of TG-1101 in patients with MS at the American Academy of Neurology (AAN) annual meeting
Reaffirming 2017 Milestones

Present updated clinical data including the full Phase 3 GENUINE data at a major medical meeting in the first half of 2017
Present clinical data from the Phase 2 Multiple Sclerosis (MS) trial
Initiate a global Phase 3 trial in MS
Complete the first interim analysis in the UNITY-CLL Phase 3 trial
Complete the first interim analysis in the UNITY-DLBCL trial
Meet with the FDA to review the Phase 3 GENUINE data and discuss suitability for filing for accelerated approval
Present new and updated data from ongoing trials at various scientific meetings throughout the year, including the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December
Financial Results for the First Quarter 2017

Cash Position: Cash, cash equivalents, investment securities, and interest receivable were $109.5 million as of March 31, 2017.

R&D Expenses: Research and development (R&D) expense was $22.7 million for the three months ended March 31, 2017 compared to $11.6 million for the three months ended March 31, 2016. Included in research and development expense for the three months ended March 31, 2017 and 2016, was $5.3 million and $4.3 million, respectively, of manufacturing and CMC expenses for Phase 3 clinical trials and potential commercialization. The increase in R&D expenses for the three months ended March 31, 2017, is primarily due to the ongoing clinical development programs and related manufacturing costs for TG-1101 and TGR-1202.

G&A Expenses: General and administrative (G&A) expense was $5.0 million for the three months ended March 31, 2017 as compared to $2.4 million for the three months ended March 31, 2016. The period-over-period increase in G&A expenses for the three months ended March 31, 2017 relates primarily to non-cash compensation expenses related to equity incentive grants recognized during 2017. Other G&A expenses for the three months ended March 31, 2017 remained relatively flat compared to the first quarter of 2016, and we expect G&A expenses to remain relatively constant through the remainder of 2017.

Net Loss: Net loss was $27.7 million for the three months ended March 31, 2017 compared to a net loss of $13.8 million for the three months ended March 31, 2016.

Financial Guidance: The Company believes its cash, cash equivalents, investment securities, and interest receivable of $109.5 million as of March 31, 2017 will be sufficient to fund the Company’s planned operations through 2018.

On May 5, 2017 Oncolytics Biotech Inc. (TSX: ONC) (OTCQX: ONCYF) (Oncolytics or the Company) reported its financial results and operational highlights for the quarter ended March 31, 2017 (Filing, Q1, Oncolytics Biotech, 2017, MAY 5, 2017, View Source [SID1234518878]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The last six months – particularly defining our clinical development plan and data announced at AACR (Free AACR Whitepaper) – have been exciting for us," said Dr. Matt Coffey, President and CEO of Oncolytics Biotech. "The compelling and statistically significant overall survival data from the IND 213 study in metastatic breast cancer presented at AACR (Free AACR Whitepaper) led us to select this indication as our registration pathway. This is part of our broader clinical development plan, which is focused on exploiting REOLYSIN’s mechanism of action incorporating both cancer cell lysis and immune system priming and activation."

Selected Highlights

Since January 1, 2017, selected highlights announced by the Company include:

Clinical Results

· Presented at the American Academy of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, in Washington, D.C., by the Canadian Cancer Trials Group at Queen’s University in Kingston, Ontario covering findings from IND 213, an open-label, randomized, phase 2 study to assess the therapeutic combination of intravenously-administered REOLYSIN given in combination with paclitaxel versus paclitaxel alone in patients with advanced or metastatic breast cancer. Results showed a statistically significant improvement in median overall survival from 10.4 months in the control arm to 17.4 months in the test arm.
· Announced registration pathway and clinical development plan with the dual objectives of obtaining regulatory approval for REOLYSIN based on the compelling metastatic breast cancer survival data recently presented at the AACR (Free AACR Whitepaper) Annual Meeting, in Washington, D.C., and expanding REOLYSIN into commercially valuable new treatment areas that include immunotherapy and immunomodulatory (IMiD) agents in collaboration with pharmaceutical partners.
· Announced, in collaboration with Celgene and cancer charity Myeloma UK, the launch of MUK eleven, a first-of-its-kind immunotherapy trial that aims to modulate the immune system to target myeloma. The phase 1b trial will study REOLYSIN in combination with Celgene’s IMiD’s, Imnovid (pomalidomide) and Revlimid (lenalidomide), as a rescue treatment in relapsing myeloma patients.
Corporate

· Appointed Oncolytics co-founder and long-serving senior executive Matt Coffey PhD, MBA, as President and CEO.
Financial

· At March 31, 2017, the Company reported $10.1 million in cash, cash equivalents and short-term investments.
· As at May 4, 2017, the Company had an unlimited number of authorized common shares with 121,836,722 common shares issued and outstanding, and 8,032,827 options outstanding (with exercise prices ranging between $0.26 and $6.72 and expiry dates ranging from 2017 to 2027).


ONCOLYTICS BIOTECH INC.
INTERIM CONSOLIDATED STATEMENTS OF FINANCIAL POSITION
(unaudited)

As at March 31,
2017
$ December 31,
2016
$
Assets
Current assets
Cash and cash equivalents 10,102,393 12,034,282
Short-term investments — 2,088,800
Accounts receivable 36,484 54,406
Prepaid expenses 182,897 260,841
Total current assets 10,321,774 14,438,329

Non-current assets
Property and equipment 301,534 319,955
Total non-current assets 301,534 319,955

Total assets 10,623,308 14,758,284
Liabilities And Shareholders’ Equity
Current Liabilities
Accounts payable and accrued liabilities 3,348,766 4,068,664
Total current liabilities 3,348,766 4,068,664

Shareholders’ equity
Share capital
Authorized: unlimited
Issued:
March 31, 2017 – 121,258,222
December 31, 2016 – 121,258,222 262,311,325 262,321,825
Contributed surplus 26,776,933 26,643,044
Accumulated other comprehensive income 533,312 554,060
Accumulated deficit (282,347,028) (278,829,309)
Total shareholders’ equity 7,274,542 10,689,620
Total liabilities and equity 10,623,308 14,758,284



ONCOLYTICS BIOTECH INC.
INTERIM CONSOLIDATED STATEMENTS OF LOSS AND COMPREHENSIVE LOSS
(unaudited)

2017 2016
For the three month period ending March 31 $ $

Expenses
Research and development 2,268,071 2,726,129
Operating 1,300,300 1,360,412
Operating loss (3,568,371) (4,086,541)
Interest 50,715 69,621
Loss before income taxes (3,517,656) (4,016,920)
Income tax (expense) recovery (63) 145
Net loss (3,517,719) (4,016,775)
Other comprehensive income items that may be
reclassified to net loss
Translation adjustment (20,748) (170,059)

Net comprehensive loss (3,538,467) (4,186,834)
Basic and diluted loss per common share (0.03) (0.03)

Weighted average number of shares (basic and diluted) 121,258,222 118,119,985


ONCOLYTICS BIOTECH INC.
INTERIM CONSOLIDATED STATEMENTS OF CHANGES IN EQUITY
(unaudited)


Share Capital
$
Contributed
Surplus
$
Accumulated
Other
Comprehensive
Income
$
Accumulated
Deficit
$
Total
$
As at December 31, 2015 261,324,692 26,277,966 760,978 (263,689,330) 24,674,306
Net loss and other comprehensive loss — — (170,059) (4,016,775) (4,186,834)
Issued, pursuant to "At the Market" Agreement 274,805 — — — 274,805
Share issue costs (375,349) — — — (375,349)
Share based compensation — 81,640 — — 81,640
As at March 31, 2016 261,224,148 26,359,606 590,919 (267,706,105) 20,468,568


Share Capital
$
Contributed
Surplus
$
Accumulated
Other
Comprehensive
Income
$
Accumulated
Deficit
$
Total
$
As at December 31, 2016 262,321,825 26,643,044 554,060 (278,829,309) 10,689,620
Net loss and other comprehensive loss — — (20,748) (3,517,719) (3,538,467)
Share issue costs (10,500) — — — (10,500)
Share based compensation — 133,889 — — 133,889
As at March 31, 2017 262,311,325 26,776,933 533,312 (282,347,028) 7,274,542



ONCOLYTICS BIOTECH INC.
INTERIM CONSOLIDATED STATEMENTS OF CASH FLOWS
(unaudited)

2017 2016
For the three month period ending March 31 $ $

Operating Activities
Net loss for the period (3,517,719) (4,016,775)
Amortization – property and equipment 24,036 45,942
Share based compensation 133,889 81,640
Unrealized foreign exchange loss 52,032 141,295
Net change in non-cash working capital (637,646) 724,655
Cash used in operating activities (3,945,408) (3,023,243)

Investing Activities
Acquisition of property and equipment (5,836) —
Redemption (purchase) of short-term investments 2,088,800 (27,823)
Cash provided by (used in) investing activities 2,082,964 (27,823)

Financing Activities
"At the Market" equity distribution agreement (10,500) (100,544)
Cash used in financing activities (10,500) (100,544)
Decrease in cash (1,872,944) (3,151,610)
Cash and cash equivalents, beginning of period 12,034,282 24,016,275
Impact of foreign exchange on cash and cash equivalents (58,945) (631,257)
Cash and cash equivalents, end of period 10,102,393 20,233,408


To view the Company’s Fiscal 2017 First Quarter Consolidated Financial Statements, related Notes to the Consolidated Financial Statements, and Management’s Discussion and Analysis, please see the Company’s annual filings, which will be available under the Company’s profile at www.sedar.com and on Oncolytics’ website at View Source

On May 5, 2017 CytomX Therapeutics, Inc. (Nasdaq:CTMX), a biopharmaceutical company developing investigational Probody therapeutics for the treatment of cancer, reported first quarter 2017 financial results (Press release, CytomX Therapeutics, MAY 5, 2017, View Source [SID1234518867]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As of March 31, 2017, CytomX had cash, cash equivalents and short-term investments of $162.5 million. After the quarter, CytomX will receive $200 million from Bristol-Myers Squibb as part of the previously announced worldwide collaboration extension. This payment will be reflected in the second quarter financial results based on the transaction close date of April 24, 2017, under the Hart-Scott-Rodino Antitrust Improvements Act. Based upon its current operating plan, the Company expects its existing capital resources will be sufficient to fund operations at least through 2019.

"The first quarter was highly productive for CytomX as we continued to rapidly progress our diverse pipeline of potentially transformative Probody therapeutics. During the quarter, we treated the first patients in the PROCLAIM-CX-072 clinical trial, filed the Investigational New Drug (IND) application for CX-2009 and moved CX-2029 into IND-enabling studies," said Sean McCarthy, D.Phil., president and chief executive officer of CytomX Therapeutics. "We also entered into a major expansion of our foundational strategic alliance with Bristol-Myers Squibb, that emphasizes their belief in the power of the Probody platform and that will strengthen our balance sheet."

Business Highlights and Recent Developments

PROCLAIM-CX-072 (PD-L1 Probody) Program

Enrollment in the initial monotherapy dose-escalation arm is progressing on plan in the PROCLAIM clinical study of CX-072, a PD-L1-targeting Probody therapeutic for the treatment of cancer patients.
The CX-072 combination arms with Yervoy (ipilimumab) and Zelboraf (vemurafenib) are expected to open in the second half of 2017.
PROCLAIM-CX-2009 (CD166 Probody Drug Conjugate) Program

In April, CytomX filed the IND for CX-2009, a first-in-class Probody drug conjugate targeting the highly expressed tumor antigen, CD166.
Phase 1/2 trial initiation is expected mid-year in multiple CD166-positive tumor types.
Partnerships

Expanded the 2014 worldwide collaboration with Bristol-Myers Squibb (BMS) to include up to six additional oncology targets and two non-oncology targets using CytomX’s proprietary Probody platform.
CytomX will receive a $200 million upfront payment and additional research funding, milestones and royalties.
The expansion takes total milestones under the alliance to more than $5 billion and represents one of the largest platform deals in recent years.
BMS has initiated IND-enabling studies for a CTLA-4-directed Probody therapeutic discovered within the collaboration. Clinical initiation is anticipated by early 2018.
CX-2029, a CD-71-directed Probody therapeutic in co-development with AbbVie, has progressed into IND-enabling studies with an IND filing anticipated in 2018.
First Quarter Financial Results
Cash, cash equivalents and investments totaled $162.5 million as of March 31, 2017, compared to $181.9 million as of December 31, 2016.

Revenue was $11.7 million for the three months ended March 31, 2017, compared to $2.2 million for the three months ended March 31, 2016. The increase was primarily attributable to $6.5 million in recognized revenue triggered by the Company’s delivery of a development and commercialization license to ImmunoGen in connection with its collaboration with ImmunoGen, which was entered in January 2014, an increase of $1.6 million in recognized revenue related to BMS’s third and fourth target selections under the collaboration, and an increase of $1.4 million in recognized revenue related to upfront payment received from AbbVie pursuant to a collaboration entered in April 2016.

Research and development expenses were $14.6 million for the three months ended March 31, 2017, compared to $13.4 million for the three months ended March 31, 2016. The increase was primarily attributable to $1.9 million to advance the Company’s CX-072 and CX-2009 into Phase 1/2 clinical development, an increase of $1.0 million in personnel-related expenses due to an increase in headcount, an increase of $1.0 million in facilities-related expenses relating to the Company’s relocation to a larger facility in October 2016, and an increase of $0.6 million in costs related to acquisitions made with respect to the Company’s patent portfolio. Expenses were partly offset by a decrease of $2.7 million in manufacturing costs for the Company’s CX-072 and CX-2009 programs, a decrease of $0.3 million in royalty payments due to BMS’s third target selection in January 2016, and a decrease of $0.3 million in professional and outside services.

General and administrative expenses were $5.7 million for the three months ended March 31, 2017, compared to $5.0 million for the three months ended March 31, 2016. The increase was attributable to $0.4 million in personnel-related expenses due to an increase in headcount and an increase of $0.3 million in non-cash stock based compensation due to increase in headcount.

On May 5, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN), a global biotechnology company, reported that it has agreed to terminate its license agreement with Immunomedics, Inc. (Nasdaq: IMMU) for sacituzumab govitecan (IMMU-132) and settle the related litigation (Press release, Seattle Genetics, MAY 5, 2017, View Source [SID1234518861]). The license agreement had not yet closed due to legal action brought by an Immunomedics stockholder challenging the transaction. The termination and settlement remain subject to court approval.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The Immunomedics transaction would have effectively utilized our substantial expertise in antibody-drug conjugate (ADC) development to advance IMMU-132 for patients in need," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "However, due to significant delays and lack of progress towards closing the deal, we are turning our full attention and resources to our promising pipeline and the substantial opportunities in front of us, including the upcoming topline data readout from the ADCETRIS ECHELON-1 trial and ongoing or planned pivotal trials of vadastuximab talirine (SGN-CD33A) and enfortumab vedotin (ASG-22ME)."

Effective upon the termination of the license, the parties have agreed to fully settle, resolve and release each other from all disputes, claims and liabilities. As part of the termination, Seattle Genetics will continue to hold 3.0 million shares of Immunomedics common stock, as well as a warrant to purchase an additional 8.7 million shares at $4.90 per share exercisable until December 31, 2017.

On May 5, 2017 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the European Commission has approved KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) and brentuximab vedotin (BV), or who are transplant-ineligible and have failed BV (Press release, Merck & Co, MAY 5, 2017, View Source [SID1234518858]). The approval allows marketing of KEYTRUDA in all 28 EU member states plus Iceland, Lichtenstein and Norway, at the approved dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Today’s approval brings an important new treatment option to patients in Europe with classical Hodgkin lymphoma who have not responded to existing therapies," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "This milestone underscores our commitment to evaluating KEYTRUDA in diseases with unmet need facing the hematology community."

"For patients with classical Hodgkin lymphoma who have not been successfully treated with prior therapies – many of whom are young and have a poor prognosis – there are limited options and treating the disease poses significant challenges," said Pier Luigi Zinzani, M.D., Ph.D., associate professor of hematology, Institute of Hematology "L. e A. Seràgnoli," University of Bologna. "With this approval, we will now be able to provide these patients with a much-needed new treatment option."

Data Supporting the Approval

The approval was based on data in 241 patients from the KEYNOTE-087 and KEYNOTE-013 trials. These multicenter, open-label studies evaluated patients with cHL who failed ASCT and BV, who were ineligible for ASCT because they were unable to achieve a complete or partial remission after salvage chemotherapy and failed BV, or who failed ASCT and did not receive BV. Both studies included patients regardless of PD-L1 expression. Patients with active, non-infectious pneumonitis, an allogeneic transplant within the past five years (or more than five years but with graft-versus-host-disease [GVHD]), active autoimmune disease or a medical condition that required immunosuppression were ineligible for either trial. The major efficacy outcome measures, overall response rate (ORR) and complete remission rate (CRR), were assessed by blinded independent central review according to the 2007 revised International Working Group (IWG) criteria. Secondary efficacy outcome measures were duration of response, progression-free survival, and overall survival.

In KEYNOTE-087, 210 patients received KEYTRUDA (pembrolizumab) at a dose of 200 mg every three weeks until unacceptable toxicity or documented disease progression. Eighty-one percent of patients were refractory to at least one prior therapy, including 35 percent who were refractory to first-line therapy. Additionally, 61 percent of patients had undergone prior ASCT, 38 percent were transplant ineligible; 17 percent had no prior BV use and 36 percent of patients had prior radiation therapy. Efficacy analysis showed an ORR of 69 percent (95% CI: 62.3, 75.2) with a CRR of 22 percent and a partial remission rate (PRR) of 47 percent. The median follow-up time was 10.1 months. Among the 145 responding patients, the median duration of response was 11.1 months (range 0.0+ to 11.1), with 76 percent of responding patients having responses of six months or longer.

In KEYNOTE-013, 31 patients received KEYTRUDA at a dose of 10 mg/kg every two weeks until unacceptable toxicity or documented disease progression. Eighty-seven percent of patients were refractory to at least one prior therapy, including 39 percent who were refractory to first-line therapy. Seventy-four percent of patients had undergone prior ASCT, 26 percent were transplant ineligible, and 42 percent of patients had prior radiation therapy. Efficacy analysis showed an ORR of 58 percent (95% CI: 39.1, 75.5) with a CRR of 19 percent and a PRR of 39 percent. The median follow-up time was 28.7 months. Among the 18 responding patients, the median duration of response was not reached (range 0.0+ to 26.1+), with 80 percent of patients with a response of six months or longer and 70 percent of patients with a response of 12 months or longer.

The safety analysis supporting the European approval of KEYTRUDA (pembrolizumab) was based on 3,194 patients with advanced melanoma, NSCLC or cHL across four doses (2 mg/kg every three weeks, 200 mg every three weeks, or 10 mg/kg every two or three weeks) in clinical studies. The most common adverse reactions (greater than 10%) with KEYTRUDA were fatigue (22%), pruritus (15%), rash (13%), diarrhea (12%) and nausea (10%). The majority of adverse reactions reported were of Grade 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.

About Hodgkin Lymphoma

Hodgkin lymphoma is a type of lymphoma that develops in the white blood cells, called lymphocytes, which are part of the immune system. Hodgkin lymphoma can start almost anywhere – most often in lymph nodes in the upper part of the body, with the most common sites being in the chest, neck or under the arms. Worldwide, there were approximately 66,000 new cases of Hodgkin lymphoma and 25,500 people died from the disease in 2012. Classical Hodgkin lymphoma accounts for about 95 percent of all cases of Hodgkin lymphoma in developed countries.

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-dose vial.

KEYTRUDA Indications and Dosing in the U.S.

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 (pembrolizumab) 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 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.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. 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 adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or 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 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. 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 (pembrolizumab) 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 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. In addition, myelitis and myocarditis were reported in other clinical trials, including cHL, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA vs the risk of possible organ rejection in these patients.

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 (pembrolizumab).

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA on any trial, 6 patients (26%) developed graft-versus-host-disease (GVHD), one of which was fatal, and 2 patients (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor-blocking antibody before transplantation. 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.

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.

KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL and treatment was interrupted due to adverse reactions in 26% of patients. Fifteen percent (15%) of patients had an adverse reaction requiring systemic corticosteroid therapy. Serious adverse reactions occurred in 16% of patients. The most frequent serious adverse reactions (>1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; one from GVHD after subsequent allogeneic HSCT and one from septic shock. The most common adverse reactions (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

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.

There is limited experience in pediatric patients. In a study of 40 pediatric patients with advanced melanoma, PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma, patients were treated with KEYTRUDA for a median of 43 days (range 1 to 414 days), with 24 patients (60%) receiving treatment for 42 days or more. The safety profile in pediatric patients was similar to that seen in adults treated with KEYTRUDA (pembrolizumab). Toxicities that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).