On October 22, 2019 SQZ Biotechnologies (SQZ), a cell therapy company developing innovative treatments for multiple therapeutic areas, reported that the company’s Investigational New Drug (IND) application for SQZ-PBMC-HPV, a novel cellular immunotherapy of antigen presenting cells (APCs) has been cleared after submission to the U.S. Food and Drug Administration (FDA) (Press release, SQZ Biotech, OCT 22, 2019, View Source [SID1234553405]). The trial is investigating the cell therapy comprised of SQZ-engineered APCs to treat HPV+ tumors, titled SQZ-PBMC-HPV. Marking the first program to enter the clinic for the company, SQZ-PBMC-HPV is also the first trial advancing into the clinic in the SQZ-Roche collaboration developing APCs for oncology.

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Armon Sharei, PhD, founder and chief executive officer of SQZ, noted, "The FDA’s clearance of our IND is a pivotal moment for the company. SQZ has potential to bring novel cell therapies to patients addressing high unmet medical needs, and this important milestone marks the first clinical translation of our platform."

"SQZ APCs have the potential for broad impact in the oncology space. A cell therapy targeting solid tumors without the need for immune or myeloablative pre-conditioning could possibly shift the paradigm for patients," said Oliver Rosen, MD, chief medical officer of SQZ. "The preclinical data underpinning this program have shown significant tumor reduction driven by high CD8 T cell infiltration into the tumor microenvironment, alongside a favorable preclinical safety profile. We are looking forward to translating this into potentially meaningful results for patients."

The Phase 1 multi-center trial (NCT04084951) is sponsored by SQZ and will enroll in multiple cohorts to assess SQZ-PBMC-HPV as both monotherapy and in combination with Roche’s checkpoint inhibitor, atezolizumab. HLA-A*02+ patients with recurrent, locally advanced or metastatic HPV16+ head & neck, cervical, anal, penile, vulval and vaginal cancers are all eligible for the study.

About SQZ-PBMC-HPV

SQZ-PBMC-HPV is an autologous cell therapy product precisely engineered via SQZ’s Cell Squeeze platform to target HPV+ cancers. It is the first product stemming from the 2018 collaboration expansion between Roche and SQZ to develop SQZ-APCs for oncology. The SQZ APC platform is designed to present tumor antigens to the body’s endogenous CD8 T cells. By enabling presentation of the appropriate target, this approach can potentially induce powerful CD8 T cell responses in patients to attack their tumors.

On October 22, 2019 Intrepida Bio, Inc. reported as a company dedicated to the discovery and development of medicines that modulate the innate immune system to fight cancer and other diseases reported an initial $9.5 million equity investment from Sofinnova Investments and Canaan will fund investigational new drug (IND) application-enabling studies of Intrepida’s lead oncology program (Press release, Intrepida Bio, OCT 22, 2019, View Source [SID1234550283]).

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Intrepida Co-founders Joel F. Martin, Ph.D., president and chief executive officer, and Olivier Laurent, Ph.D., chief scientific officer, together with Biouniversa s.r.l., established Intrepida with worldwide rights to develop the technology based on the unique targets BAG3 and its receptor IFITM-2.

Tumors use BAG3 – IFITM-2 signaling to create an environment that promotes tumor growth and stymies the immune system from attacking the tumor. BAG3 expression is particularly strong in pancreatic ductal adenocarcinoma (PDAC), where it was detected in every single patient tested1, and high levels of BAG3 were associated with poor prognosis1. Intrepida’s anti-BAG3 antibodies block this pathway, eliminating a tumor’s pro-growth environment while encouraging the immune system to attack the tumor2. By blocking BAG3, these antibodies broadly affect an array of mechanisms that support and protect the tumor.

The prospect of BAG3 as an anti-cancer target was discovered and preclinically validated by the team at Biouniversa, led by Dr. Maria Caterina Turco, professor at the University of Salerno and chairwoman of the Intrepida Scientific Advisory Board. "In vivo and in vitro studies demonstrate that Intrepida’s anti-BAG3 antibodies slow tumor growth, decrease metastases and improve survival," said Joel Martin, Ph.D., co-founder, president and chief executive officer of Intrepida Bio. "We’ve seized this exceptional opportunity to fully develop these compounds with a goal to begin clinical trials with our lead candidate IB001 in 2021."

"Joel and Olivier searched for and found truly novel, validated targets that alter the body’s first line of defense – the innate immune system – to fight disease. I am confident the Intrepida team will conduct a rigorous program to build the clinical evidence around BAG3," said Mike Powell, Ph.D., general partner at Sofinnova Investments and chairman of the Intrepida Board of Directors.

In addition to Dr. Powell, existing Intrepida directors include David Kabakoff, Ph.D., executive partner of Sofinnova; Nina Kjellson, general partner at Canaan; Ellen Lubman, chief business officer at Impel NeuroPharma; and Dr. Martin. New directors include Elizabeth Robinson, Ph.D., co-founder and vice chairman of Indaco Venture Partners SGR and Giovanni Rizzo, Ph.D., chief executive officer of Biouniversa. Biouniversa’s original investors, Indaco Venture Partners and Vertis SGR, have joined Intrepida’s investor syndicate. The Indaco and Vertis investments were led by Dr. Robinson and Mauro Odorico, respectively.

1Expression of the antiapoptotic protein BAG3 is a feature of pancreatic adenocarcinoma and its overexpression is associated with poorer survival. Rosati, Alessandra et al., Am J Pathol. 2012 Nov;181(5):1524-9.
2BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages. Rosati, Alessandra et al., Nat Commun. 2015 Nov 2;6:8695.

On October 22, 2019 OPKO Health, Inc. ("OPKO Health" or the "Company") (NASDAQ:OPK) reported that, subject to market and other conditions, it intends to offer and sell up to $100 million of shares of its common stock (the "Shares") in an underwritten public offering (Press release, Opko Health, OCT 22, 2019, View Source [SID1234542443]). The Company intends to grant the underwriters an option for a period of 30 days to purchase up to an additional 15% of the number of Shares to be issued and sold in the offering.

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The Company intends to use the net proceeds received from the offering of the Shares to fund research and development to further develop and commercialize its portfolio of proprietary pharmaceutical and diagnostic products and for working capital, capital expenditures, acquisitions and other general corporate purposes.

Jefferies LLC, Piper Jaffray & Co. and Guggenheim Securities, LLC will act as joint book-running managers for the offering.

The offering of the Shares will be made by means of a prospectus supplement to the prospectus forming a part of the Company’s effective shelf registration statement on Form S-3 (Registration No. 333-229400) filed with the Securities and Exchange Commission (the "SEC") on January 28, 2019 and other related documents. You may obtain these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the preliminary prospectus supplement may be obtained from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY, 10022, by email at [email protected] or by phone at +1 877 821 7388; Piper Jaffray & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by email at [email protected] or by phone: 1-800-747-3924; and Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by email at [email protected] or by phone at +1 212 518 5548. Before you invest, you should read the prospectus supplement and the accompanying base prospectus along with other documents that the Company has filed with the SEC for more complete information about the Company and these offerings.

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

On October 22, 2019 Revolution Medicines, Inc., a clinical-stage oncology company focused on developing targeted therapies to inhibit elusive frontier targets within notorious cancer pathways, reported that preclinical in vivo data on the company’s novel inhibitors of oncogenic RAS(ON) mutants will be presented at the 2019 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Revolution Medicines, OCT 22, 2019, View Source [SID1234542428]). Presented findings will highlight the ability of the company’s inhibitors to overcome adaptive resistance mechanisms and drive xenograft regressions in in vivo models. The 2019 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) is being held October 26-30, 2019 in Boston, MA.

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Leveraging its proprietary tri-complex technology platform, Revolution Medicines is developing a portfolio of targeted RAS compounds that it believes are the first potent, mutant-selective, cell-active inhibitors of the active, GTP-bound form of RAS, or RAS(ON). Initially, the company is prioritizing four mutant RAS(ON) targets, KRASG12C, KRASG13C, KRASG12D and NRASG12C.

The data on the company’s active RAS(ON) inhibitors will be reported in podium and poster presentations entitled, "Tri-complex inhibitors of the oncogenic, GTP-bound form of KRASG12C overcome RTK-mediated escape mechanisms and drive tumor regressions in vivo." Details of the presentations are as follows:

Podium Presentation #PR10:

Session: Spotlight on Proffered Papers 3
Presenting Author: Christopher Schulze, Ph.D., senior scientist at Revolution Medicines
Date/Time: Tuesday, October 29, 2019, 12:20 – 12:30 p.m. Eastern
Location: Level 3 Ballroom AB Lobby
Poster Presentation #B077:

Session: Poster Session B: MAPK Pathways 1
Presenting Author: Christopher Schulze, Ph.D., senior scientist at Revolution Medicines
Date/Time: Monday, October 28, 2019, 12:30 – 4:00 p.m. Eastern
Location: Level 2 – Hall D
In addition to the presentations on its mutant RAS inhibitors, Revolution Medicines will also report preclinical data from its 4EBP1/mTORC1 program in a poster presentation at the conference. The presented findings will highlight results of the company’s work in identifying a potential biomarker of response to selective mTORC1 inhibitors. Details of that presentation are as follows:

Poster Presentation #B108:

Title: 4EBP3 mRNA as a biomarker of therapeutic response to treatment with mTORC1 inhibitors
Presenting Author: Bianca Lee, Ph.D., scientist at Revolution Medicines
Session: Poster Session B: mTOR/PI3-Kinase
Date/Time: Monday, October 28, 2019, 12:30 – 4:00 p.m. Eastern
Location: Level 2 – Hall D

On October 22, 2019 EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, reported on behalf of the global strategic alliance with Pfizer three-year results from Part A of the pivotal Phase II JAVELIN Merkel 200 trial regarding long-term overall survival and durable responses in patients with previously treated metastatic Merkel cell carcinoma (mMCC) who received avelumab (BAVENCIO) (Press release, EMD Serono, OCT 22, 2019, View Source [SID1234542427]).1 In this exploratory analysis, the overall survival (OS) rate at three years was 32%; the median duration of response (DOR) was 40.5 months; and the objective response rate (ORR) was 33.0%, which was unchanged from the one-year analysis.1 These data will be presented at the First International Symposium on Merkel Cell Carcinoma in Tampa, Florida on October 21-22, 2019.

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"Historically, chemotherapy has been the only treatment for advanced Merkel cell carcinoma, with responses lasting for less than one year. In this updated analysis of the JAVELIN Merkel 200 trial, up to one-third of patients with this disease who received avelumab were alive at three years," said Sandra P. D’Angelo, M.D., study global principal investigator, medical oncologist at Memorial Sloan Kettering Cancer Center. "The durability of clinical response and survival outcomes from avelumab treatment in this setting with three years of follow-up underscore the benefits of this medicine in the treatment of patients with metastatic Merkel cell carcinoma."

Results from the Phase II, open-label, single-arm, multicenter JAVELIN Merkel 200 study supported the U.S. Food and Drug Administration (FDA) accelerated approval of BAVENCIO for mMCC in 2017. The analysis presented today shows that with a minimum follow-up of 36 months and a median follow-up of 40.8 months (range: 36.4–49.7), the ORR was 33.0% (95% CI: 23.3%, 43.8%) and median DOR was 40.5 months (95% CI: 18.0, NE). Among the 11.4% (10/88) of patients with complete responses (CR), half (n=5) had an ongoing response at the data cutoff. Progression-free survival (PFS) rates were 26% (95% CI: 17%, 36%) at two years and 21% (95% CI: 12%, 32%) at three years. Median OS was 12.6 months (95% CI: 7.5, 17.1), and OS rates were 36% (95% CI: 26%, 46%) at two years and 32% (95% CI: 23%, 42%) at three years.1 An analysis of OS compared to historical control data was not part of this analysis.

No unanticipated adverse events (AEs) or late infusion-related reactions occurred with long-term treatment. Treatment-related AEs of any grade occurred in 77.3% of patients (grade ≥3 in 11.4%); 21.6% had an immune-related AE of any grade (grade ≥3 in 4.5%).1

About JAVELIN Merkel 200
JAVELIN Merkel 200 is a Phase II, open-label, single-arm, multicenter study. Part A included 88 patients with Stage IV mMCC whose disease had progressed on or after chemotherapy administered for distant metastatic disease. The primary endpoint in Part A was best overall response (BOR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by a blinded independent central review committee (IRC); secondary endpoints included IRC-assessed DOR and PFS by RECIST 1.1; OS; and safety and tolerability. Part B included 116 patients with mMCC who were treatment-naïve to systemic therapy in the metastatic setting. For Part B, the major efficacy outcome measure was durable response, defined as objective response (complete response or partial response) with a duration of at least six months; secondary outcome measures included BOR, DOR, PFS and OS. Patients received BAVENCIO 10 mg/kg as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.1

About Merkel Cell Carcinoma
Metastatic MCC is a rare and aggressive disease in which cancer cells form in the top layer of the skin, close to nerve endings.2,3 MCC, which is also known as neuroendocrine carcinoma of the skin or trabecular cancer, often starts in those areas of skin that are most often exposed to the sun, including the head, neck and arms.4,5 Risk factors for MCC include sun exposure and infection with Merkel cell polyomavirus.6 Caucasian males older than 50 are at increased risk.7 MCC is often misdiagnosed as other skin cancers and grows at an exponential rate on chronically sun-damaged skin.5,8

About BAVENCIO (avelumab)
BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.9-11 BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.11-13 In November 2014, EMD Serono and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications
In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in more than 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

BAVENCIO (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

BAVENCIO Important Safety Information from the US FDA-Approved Label
BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% of patients, including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% of patients, including two (0.1%) patients with Grade 5, and 11 (0.6%) with Grade 3.

BAVENCIO in combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold BAVENCIO and axitinib for moderate (Grade 2) hepatotoxicity and permanently discontinue the combination for severe or life-threatening (Grade 3 or 4) hepatotoxicity. Administer corticosteroids as needed. In patients treated with BAVENCIO in combination with axitinib, Grades 3 and 4 increased ALT and AST occurred in 9% and 7% of patients, respectively, and immune-mediated hepatitis occurred in 7% of patients, including 4.9% with Grade 3 or 4.

BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis until resolution. Permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated colitis occurred in 1.5% of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal insufficiency was reported in 0.5% of patients, including one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were reported in 6% of patients, including three (0.2%) with Grade 3.

Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade ≥3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% of patients, including two cases of Grade 3 hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% of patients.

BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse reactions occurred in less than 1% of 1738 patients treated with BAVENCIO as a single agent or in 489 patients who received BAVENCIO in combination with axitinib: myocarditis including fatal cases, pancreatitis including fatal cases, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic inflammatory response.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.

BAVENCIO in combination with axitinib can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue BAVENCIO and axitinib for Grade 3-4 cardiovascular events. MACE occurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with axitinib compared to 3.4% treated with sunitinib. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥ 20%) in patients with metastatic Merkel cell carcinoma (MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash (22%), decreased appetite (20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades, ≥ 20%) in patients with metastatic MCC were lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine aminotransferase (20%).

The most common adverse reactions (all grades, ≥ 20%) in patients with locally advanced or metastatic urothelial carcinoma (UC) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased appetite/hypophagia (21%), and urinary tract infection (21%).

Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in patients with locally advanced or metastatic UC were hyponatremia (16%), increased gamma-glutamyltransferase (12%), lymphopenia (11%), hyperglycemia (9%), increased alkaline phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia (3%), and increased aspartate aminotransferase (3%).

Fatal adverse reactions occurred in 1.8% of patients with advanced renal cell carcinoma (RCC) receiving BAVENCIO in combination with axitinib. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

The most common adverse reactions (all grades, ≥20%) in patients with advanced RCC receiving BAVENCIO in combination with axtinib (vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).

Please see full US Prescribing Information and Medication Guide available at View Source

About Merck KGaA, Darmstadt, Germany-Pfizer Alliance
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany and Pfizer. The global strategic alliance between Merck KGaA, Darmstadt, Germany and Pfizer enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of BAVENCIO, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens, and is striving to find new ways to treat cancer.

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