Strata Oncology Expands Strata PATH Trial to Eight Sarah Cannon Research Institute Sites

On August 16, 2022 Strata Oncology, Inc., a next-generation precision oncology company enabling smarter and earlier cancer treatment, reported that Sarah Cannon Research Institute (SCRI) has joined the Strata Precision Indications for Approved THerapies (Strata PATH) trial (Press release, Strata Oncology, AUG 16, 2022, View Source [SID1234618437]). Researchers will enroll patients at eight SCRI-affiliated sites including:

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!

Florida Cancer Specialists (4 sites)
Genesis Cancer and Blood Institute, Hot Springs, AR
Hematology Oncology Clinic, Baton Rouge, LA
Tennessee Oncology, Chattanooga, TN
Zangmeister Cancer Center, Columbus, OH
Strata PATH is a prospective pan-tumor therapeutic trial designed to evaluate the efficacy and safety of multiple FDA-approved cancer therapies in new, biomarker-guided patient populations. A range of therapeutic classes will be evaluated across tumor types, including targeted therapies, antibody-drug conjugates, immunotherapies, and angiogenesis inhibitors.

"Strata is thrilled to partner with SCRI to bring new advances and increased options to patients with both late-stage and early-stage cancer," said Dan Rhodes, Ph.D., co-founder and Chief Executive Officer, Strata Oncology. "In the Strata PATH trial, we are investigating how our innovative molecular profiling platform and our novel quantitative RNA algorithms can be used to optimize and expand the use of cancer treatments across therapeutic classes. Partnering with leading organizations like SCRI is integral to expanding the reach of this transformative clinical trial."

"The Strata PATH study aligns with our mission to advance cancer therapies and offer personalized cancer care close to home," said Andrew McKenzie, Vice President, Personalized Medicine, Sarah Cannon Research Institute. "We look forward to leveraging our cutting-edge patient identification strategies to expand access to the latest therapies through the Strata PATH clinical trial."

Patients interested in learning more about the Strata PATH trial can visit ClinicalTrials.gov and search for the Strata PATH Trial identifier: NCT05097599.

About Strata PATH
The Strata Precision Indications for Approved THerapies (Strata PATH) trial, is a 700-patient prospective pan-tumor therapeutic trial designed to evaluate the efficacy and safety of multiple FDA-approved cancer therapies in new, biomarker-guided patient populations. Strata PATH will enroll patients with advanced cancer, as well as patients with early-stage cancer who have evidence of micrometastatic disease after initial treatment. All therapies being evaluated in Strata PATH are FDA-approved in oncology with demonstrated safety profiles in the advanced setting. Enrollment for multiple arms in Stata PATH is based on novel algorithms Strata Oncology developed using its clinical molecular database comprising DNA mutation profiles and quantitative RNA expression data, as well as detailed treatment history and outcome data, from tens of thousands of patients. A range of therapeutic classes will be evaluated in Strata PATH including targeted therapies, antibody-drug conjugates, immunotherapies, and angiogenesis inhibitors.

Simcha Therapeutics Accelerates Growth with Key Leadership Appointments, Expanded Research and Option Agreement with Yale School of Medicine

On August 16, 2022 Simcha Therapeutics ("Simcha"), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, reported the appointment of Sanuj Ravindran, M.D., as chief executive officer and director, and Jake Bauer as an independent member and chair of its board of directors (Press release, Simcha Therapeutics, AUG 16, 2022, View Source [SID1234618436]).

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!

Simcha has also expanded its sponsored research agreement with Yale School of Medicine related to cytokine biology in the laboratory of Aaron Ring, Ph.D., M.D., associate professor of immunobiology and Simcha founder. Through this expanded agreement, the company will support research in the Ring Laboratory focused on overcoming biological limitations of native cytokines. Simcha holds an exclusive option to license multiple therapeutic agents resulting from the expanded research agreement.

"With the support of our successful Series B financing and encouraging progress being made with ST-067 in the clinic, Simcha is entering a stage of dynamic growth with even greater opportunity ahead," said Bauer. "I’m thrilled to have joined the company earlier this year, and excited to have recruited Sanuj, a skilled and thoughtful leader, to guide Simcha as it navigates its many potential avenues for growth."

Dr. Ravindran remarked, "Simcha is built on a remarkable scientific foundation and Aaron’s bold vision that patients deserve more than incremental advances. Together these have led to the advancement of a promising first-in-class therapeutic in ST-067, our decoy resistant IL-18 agent; and created a new way forward for IL-18 as a potentially powerful and broadly applicable cancer immunotherapy pathway. As Simcha continues to explore the breadth of ST-067’s potential in the clinic, and as we accelerate the advancement of other engineered cytokines, I feel privileged to build and lead a patient and product focused organization with a commitment to pioneering truly transformational therapies."

Dr. Ravindran has spent more than 20 years in strategic and operational roles across the life science industry, both as an investor and company builder. Most recently, he served as CEO-in-residence at BridgeBio (BBIO) where he was chief executive officer of PellePharm and executive chair of Phoenix Tissue Repair. In these roles, Dr. Ravindran led the companies’ growth, directed strategy, secured significant partnerships, and advanced pipeline programs in oncology and rare skin diseases through mid- and late-stage clinical trials. Before this, he served as chief business officer at aTyr Pharma (LIFE), a clinical-stage protein therapeutics company focused on tRNA synthetases. Prior to that, Dr. Ravindran was senior vice president of corporate development at The Medicines Company (MDCO), where he led multiple transactions totaling more than $2 billion in potential value. He began his biotech career as a venture capitalist for 10 years with Burrill & Company, Radius Ventures, and Asian Healthcare Fund. Dr. Ravindran was previously a practicing physician, board-certified in Internal Medicine, having completed his residency training at Thomas Jefferson University Hospital. He received his bachelor’s degree from Northwestern University, his doctorate in medicine from Jefferson Medical College, and his master’s of business administration from the Kellogg School of Management.

Dr. Ravindran joins Beatrice McQueen, Ph.D., on the Simcha leadership team, who was recently appointed chief operating officer and has led Simcha’s finance and operations since its inception. Dr. McQueen has spent over 20 years in various operational roles, working to advance programs at leading organizations such as Amgen, PPD and Pfizer.

Bauer, having previously served as chief business officer of MyoKardia, is currently a venture partner with ARCH Venture Partners and SR One Capital Management. He and Dr. Ravindran join the Simcha board of directors with existing members Simeon George, M.D., CEO of SR One; Sean Li, Ph.D., of WuXi AppTec; Terry Rosen, Ph.D., CEO of Arcus Biosciences; and Aaron Ring, M.D., Ph.D., founder of Simcha Therapeutics.

Pharmaxis Receives Aptar Option Exercise Fees of US$5m

On August 16, 2022 Clinical stage drug developer Pharmaxis (ASX: PXS) reported it has now received US$5.0 million (A$ 7.0 million net of applicable withholding taxes) from Aptar Pharma following the exercise of its options to acquire the Pharmaxis Orbital technology as announced on 4 August 2022 (Press release, Pharmaxis, AUG 16, 2022, View Source;utm_campaign=Pharmaxis%20Receives%20Aptar%20Option%20Exercise%20Fees%20of%20US5m&utm_content=Pharmaxis%20Receives%20Aptar%20Option%20Exercise%20Fees%20of%20US5m+CID_70028764d5327ddbe643c5eef231fc83&utm_source=Campaign%20Monitor&utm_term=View%20Full%20Media%20Release [SID1234618435]).

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!

Pharmaxis reported cash funds of A$9 million at 30 June 2022 in its quarterly shareholder update and its expectation of receiving $5 million from its 2022 R&D tax incentive later in the year. The receipt from Aptar increases the Pharmaxis proforma cash balance at 30 June 2022 to A$21 million.

Pharmaxis CEO Gary Phillips said, "Over the past two years the Pharmaxis team has generated a total of $25 million of non-dilutive cash from commercial agreements related to the mannitol business, $2.5 million in Government funding won in competitive grants and R&D tax credits of $10 million1. Funding our business in this manner has only been possible because of the inherent value in our exciting pipeline of small molecule drugs and the mannitol business.

"We continue to look for additional commercial opportunities to advance our pipeline and in the meantime our focus is on delivering data from the phase 1c/2 studies in myelofibrosis and established skin scarring by the end of the year."

Propanc Biopharma Receives Notice of Allowance for Proenzyme Compositions to Treat Cancer from the European Patent Office

On August 16, 2022 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that a Notice of Allowance has been received from the European Patent Office (EPO) for claims involving compositions of proenzymes to treat cancer (Press release, Propanc, AUG 16, 2022, View Source [SID1234618430]). This is the Company’s second patent application allowed in this jurisdiction and expires in November, 2036. A third patent application is currently under examination at the EPO for a method to treat cancer stem cells, which was allowed in March this year by the US Patent and Trademark Office (USPTO).

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 field of the invention covers future dosing in planned clinical studies for the Company’s lead product candidate, PRP. The allowed patent, citing proenzyme compositions to treat cancer, comprising trypsinogen and chymotrypsinogen at specific higher dosage ratios than the Company’s original foundation patent, will enable the Company to cover higher doses in a planned, Phase I, First-In-Human study in advanced cancer patients. It is believed that increased exposure at higher doses may result in better therapeutic efficacy.

Currently, the Company’s growing IP portfolio consists of 65 patents either in force, or currently under examination in global jurisdictions. As a result of the EPO allowance, the number of patents in the portfolio is expected to increase as the Company validates the allowed patent in selected individual countries within the EU region. The Company also plans to file additional patent applications based on recent scientific discoveries through the Company’s joint research partnerships in the near future, centered on composition, method of use and process development claims.

"The advancement of our growing IP portfolio is a reflection of our tireless efforts over the last decade into research and development of proenzymes as an effective tool to treat cancer," said Mr. James Nathanielsz, Propanc’s Chief Executive Officer. "As we progress towards a First-In-Human study in advanced cancer patients, it is important to ensure adequate protection of our invention, which holds significant value for shareholders, as we continue to expand in this novel field. PRP is an exciting new approach to treat and prevent metastatic cancer by targeting and eradicating cancer stem cells (CSCs), which remains the biggest cause of death for sufferers. By targeting CSCs and leaving healthy cells alone, it may also be free from the side effects normally associated with standard treatments, which will be significant for patients and their loved ones. We remain dedicated to this cause."

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

FDA Accepts Submission of Supplemental New Drug Application for LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone for Patients With Metastatic Castration-Resistant Prostate Cancer and Grants Priority Review

On August 16, 2022 AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that a supplemental New Drug Application (sNDA) for LYNPARZA in combination with abiraterone and prednisone or prednisolone has been accepted and granted priority review by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Merck & Co, AUG 16, 2022, View Source [SID1234618429]). The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date in the fourth quarter of 2022.

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!

In the U.S., prostate cancer is the second most common cancer in male patients. Approximately 10-20% of male patients with advanced prostate cancer are estimated to develop castration resistant prostate cancer (CRPC) within five years, and at least 84% of these men may develop metastases at the time of CRPC diagnosis. Patients with advanced prostate cancer have a particularly poor prognosis, and the five-year survival rate remains low.

Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said, "There remains a critical unmet need among patients diagnosed with mCRPC, where the prognosis remains poor, and treatment options are limited. Today’s news is another step towards bringing forward a new, much-needed treatment option in this setting. If approved, LYNPARZA with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with this disease."

Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, "Merck is committed to developing new treatment options for patients with mCRPC, a complex disease that urgently needs more therapies. We look forward to working with the FDA towards the goal of bringing a new option to patients with mCRPC with or without homologous recombination repair gene mutations."

The sNDA was based on results from the Phase 3 PROpel trial, which were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium and later published in NEJM Evidence.

In PROpel, LYNPARZA in combination with abiraterone and prednisone or prednisolone reduced the risk of disease progression or death by 34% (HR=0.66 [95% CI, 0.54-0.81]; p<0.0001) versus placebo plus abiraterone and prednisone or prednisolone. Median radiographic progression-free survival (rPFS) was 24.8 months for the LYNPARZA plus abiraterone arm versus 16.6 months for the placebo plus abiraterone arm.

The safety and tolerability of LYNPARZA in combination with abiraterone and prednisone or prednisolone was in line with that observed in prior clinical trials and the known profiles of the individual medicines. The most common adverse events (AEs) (≥20%) were anemia (46%), fatigue (37%) and nausea (28%). Grade ≥3 AEs were anemia (15%), hypertension (4%), urinary tract infection (2%), fatigue (2%), decreased appetite (1%), vomiting (1%), back pain (1%), diarrhea (1%) and nausea (0.3%). Approximately 14% of patients who received LYNPARZA in combination with abiraterone and prednisone or prednisolone discontinued treatment due to an AE.

LYNPARZA is approved in the U.S. for patients with homologous recombination repair (HRR) gene-mutated mCRPC (BRCA-mutated and certain other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone and in the European Union, Japan and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent (NHA).

About PROpel

PROpel (ClinicalTrials.gov, NCT03732820) is a randomized, double-blind Phase 3 trial testing the efficacy safety, and tolerability of LYNPARZA versus placebo when given in addition to abiraterone and prednisone or prednisolone in patients with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting. The primary endpoint is rPFS, and secondary endpoints include overall survival, time to secondary progression or death and time to first subsequent therapy.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm Ovarian Cancer After 3 or More Lines of Chemotherapy

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received

LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in >25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS for LYNPARZA in the United States

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

a deleterious or suspected deleterious BRCA mutation and/or
genomic instability
Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced gBRCAm Ovarian Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer

For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm HER2-Negative Metastatic Breast Cancer

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information, including Medication Guide.

About LYNPARZA (olaparib)

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.

About metastatic castration-resistant prostate cancer

Prostate cancer is the second most common cancer in male patients globally and is associated with a significant mortality rate. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body, despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of patients with advanced prostate cancer will develop CRPC within five years, and at least 84% of these patients will have metastases at the time of CRPC diagnosis. Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.

About the AstraZeneca and Merck strategic oncology collaboration

In July 2017, AstraZeneca and Merck, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.

Merck’s focus on cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.