On May 8, 2020 AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved LYNPARZA in combination with bevacizumab as a first-line 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 (Press release, Merck & Co, MAY 8, 2020, View Source [SID1234557384]). Patients will be selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

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The approval was based on a biomarker subgroup analysis of 387 patients with HRD-positive tumors from the Phase 3 PAOLA-1 trial, which showed that LYNPARZA in combination with bevacizumab reduced the risk of disease progression or death by 67% (HR 0.33 [95% CI, 0.25-0.45]). It improved progression-free survival (PFS) to a median of 37.2 months vs. 17.7 months with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.

The most common adverse reactions (ARs) ≥10% in the overall trial population for PAOLA-1 when treated with LYNPARZA in combination with bevacizumab (N=535) and at a ≥5% frequency compared to bevacizumab alone (N=267) were fatigue (53% vs. 32%), nausea (53% vs. 22%), anemia (41% vs. 10%), lymphopenia (24% vs. 9%), vomiting (22% vs. 11%) and leukopenia (18% vs. 10%). Grade 3 or above ARs were anemia (17% vs. <1%), lymphopenia (7% vs. 1%), fatigue (5% vs. 2%), nausea (2% vs. 1%), leukopenia (2% vs. 2%) and vomiting (2% vs. 2%). Additional adverse reactions that occurred in ≥10% of patients receiving LYNPARZA in combination with bevacizumab irrespective of the frequency compared to bevacizumab alone were diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%). Fatal adverse reactions occurred in one patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received LYNPARZA in combination with bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA in combination with bevacizumab (5%) than in those receiving bevacizumab alone (1.9%). ARs led to dose interruption in 54% of patients on LYNPARZA in combination with bevacizumab, while 41% of patients on LYNPARZA in combination with bevacizumab had a dose reduction. Discontinuation of treatment due to ARs occurred in 20% of patients on LYNPARZA in combination with bevacizumab.

Approximately one in two women with advanced ovarian cancer has an HRD-positive tumor. For patients with advanced ovarian cancer, the primary aim of first-line maintenance treatment is to delay disease progression for as long as possible.

Isabelle Ray-Coquard, principal investigator of the PAOLA-1 trial and medical oncologist, Centre Léon Bérard and President of the GINECO group, said, "Ovarian cancer is a devastating disease. The magnitude of benefit in HRD-positive patients in the PAOLA-1 trial is impactful. I look forward to seeing this translate into clinical practice."

Dave Frederickson, executive vice president, head of the oncology business unit, AstraZeneca, said, "This approval represents another milestone for LYNPARZA in patients with ovarian cancer. The median progression-free survival of more than three years offers new hope for women to delay relapse in this difficult-to-treat disease. These results further establish that HRD-positive is a distinct subset of ovarian cancer and HRD testing is now a critical component of diagnosis and tailoring of treatment for women with advanced ovarian cancer."

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, "Advances in understanding the role of biomarkers and PARP inhibition have fundamentally changed how physicians treat this aggressive type of cancer. Today’s approval based on the PAOLA-1 trial highlights the importance of HRD testing at diagnosis to identify those who may benefit from LYNPARZA in combination with bevacizumab as a first-line maintenance treatment."

The full results from the Phase 3 PAOLA-1 trial were published in The New England Journal of Medicine.

Regulatory reviews are currently underway in the European Union, Japan and other countries for LYNPARZA in combination with bevacizumab as a first-line maintenance treatment for patients with advanced ovarian cancer. As part of a broad development program, LYNPARZA is being assessed as a monotherapy and in combination across multiple tumor types.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

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 <1% of patients exposed to LYNPARZA, 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.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of 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%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of 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 in clinical trials of 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 in clinical trials of 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

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of 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 in clinical trials of 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—gBRCAm, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in 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 in 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 in clinical trials of 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 in clinical trials of 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%).

DRUG INTERACTIONS

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

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of 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

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

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.

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.

Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

About PAOLA-1

PAOLA-1 is a double-blind Phase 3 trial evaluating the efficacy and safety of LYNPARZA in combination with standard-of-care bevacizumab vs. bevacizumab alone, as a first-line maintenance treatment for advanced FIGO Stage III-IV high grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to first-line treatment with platinum-based chemotherapy and bevacizumab.

PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological Trial groups) trial, sponsored by ARCAGY Research (Association de Recherche sur les CAncers dont GYnécologiques) on behalf of GINECO (Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group specializing in clinical and translational research in patients’ cancers and a member of the GCIG (Gynecologic Cancer InterGroup).

In the U.S., eligible advanced ovarian cancer patients will be selected for therapy based on the FDA-approved myChoice HRD Plus, an HRD test designed to detect when a tumor has lost the ability to repair double-stranded DNA breaks. Myriad Genetics, Inc. owns and commercializes myChoice HRD Plus.

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 Ovarian Cancer

Ovarian cancer is the fifth most common cause of death from cancer in women in the United States. This year, it is estimated that more than 21,000 women will be diagnosed with ovarian cancer and nearly 14,000 women will die of this disease.

Women with ovarian cancer are often diagnosed with advanced disease, which has a five-year survival rate of about 48%. For newly diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible. BRCA1/2 mutations are found in approximately 22% of all ovarian cancers and approximately 50% of ovarian cancers are HRD-positive.

About Homologous Recombination Deficiency

HRD encompass a wide range of genetic abnormalities, including BRCA mutations, that can be detected using tests. As the BRCA gene drives DNA repair via homologous recombination, mutation of this gene leads to homologous recombination deficiency thereby interfering with normal cell DNA repair mechanisms. BRCA mutations are just one of many HRDs which confer sensitivity to PARP inhibitors including LYNPARZA.

About the AstraZeneca and Merck Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, 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.

On May 8, 2020 NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX) a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported the successful completion of its capital increase by issuing new ordinary shares with exclusion of pre-emptive subscription rights, via a private placement to European investors through an accelerated bookbuilding process, for approximately € 5.5 million (Press release, NOXXON, MAY 8, 2020, View Source [SID1234557418]).

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"We would like to thank the new shareholders who participated in this financing to support NOXXON’s strategy. This capital increase strengthens our financial visibility to well over a year under the current business plan. It also gives us the flexibility to plan for the future and to consider new projects creating value with NOXXON compounds in addition to the ongoing NOX-A12 Phase 1/2 trial in combination with radiotherapy as a first-line treatment for brain cancer patients. Obtaining data from the NOX-A12 brain cancer trial remains one of NOXXON’s top clinical goals," said Aram Mangasarian, CEO of NOXXON.

Dave van Mastwijk, Partner at Nyenburgh Investment Partners (NYIP), as the major investor of the private placement commented "NOXXON is a perfect fit in our portfolio, which is focused on highly promising biotech companies in Europe. We believe that NOXXON’s unique technology holds promise in a multitude of applications. This investment allows us to help finance and expand NOXXON for the coming years, in which we expect to see significant value creation and appreciation. We look forward to becoming a major shareholder in NOXXON."

The Supervisory Board decided on May 08, 2020 to proceed with a capital increase excluding of shareholders’ pre-emptive rights, in accordance with the delegation granted to it by the sixth resolution of the extraordinary general meeting of Shareholders of January 02, 2019. All the subscriptions were received and the final completion of the capital increase was acknowledged by the Board of Directors at its meeting held on May 08, 2020.

The total amount of the capital increase amounts to € 5,500,000 and corresponds to the issue of 10,784,314 new shares at a subscription price of € 0.51 per new share, i.e. a dilution rate of 29.5% of the capital after operation on a non-diluted basis. The subscription price of € 0.51 per new share represents a discount of 31.1% on the average closing price of the shares over the seven trading days from April 29, 2020 to May 08, 2020.

Settlement of the transaction will take place on May 12, 2020. The new shares will carry current dividend rights and will be admitted to trading on the Euronext Growth Paris market, on the same trading line as the existing shares, under ISIN code NL0012044762, as of May 13, 2020.

The company’s issued share capital, which is currently composed of 25,737,422 shares, will therefore be composed of 36,521,736 shares after the transaction. As an indication, the participation of a shareholder holding 1% of the company’s issued share capital prior to the capital increase (calculated on the basis of the number of shares of the company’s issued share capital as of May 06, 2020), would be, after the issuance of the 10,784,314 new shares, 0.70% of the capital. The issued share capital prior to this financing was € 257,374.22 and will therefore become € 365,217.36.

In connection with the private placement, the company entered into a lock-up period of 30 calendar days following the settlement of the new shares.

The capital increase was advised by INVEST CORPORATE FINANCE and managed by INVEST SECURITIES acting as Lead Manager and Bookrunner.

Detailed information about NOXXON, including information about its business, results and corresponding risk factors, was presented in the Annual Report 2019 and in the related press release dated April 22, 2020. The company’s press releases as well as other regulated information can be found on the company’s website (www.noxxon.com).

On May 8, 2020 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported financial results and provided a business update for the first quarter ended March 31, 2020 (Press release, Mersana Therapeutics, MAY 8, 2020, View Source [SID1234557385]).

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"The Phase 1 dose escalation study demonstrates that XMT-1536 is well tolerated, without the severe neutropenia, peripheral neuropathy, or ocular toxicity commonly seen with other ADC platforms, and delivers confirmed responses and durable stable disease in heavily-pretreated patients. We will provide an early look at the Phase 1 dose expansion data on a conference call and at the upcoming ASCO (Free ASCO Whitepaper) virtual scientific program and remain on track to reach our goal of progressing XMT-1536 through proof of concept and into registration-enabling studies," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "The COVID-19 crisis has certainly caused disruption, and we are immensely thankful to those healthcare professionals on the front lines who continue to support patients during these uncertain times. Despite the impact of this crisis, we have continued to advance all our novel ADC programs. We will move forward guided by the knowledge that cancer patients with significant unmet medical need are still waiting for clinically meaningful treatment options."

Recent Highlights and Updates

Clinical Programs

·Reported updated data from XMT-1536 Phase 1 dose escalation. On March 30, 2020, the Company reported updated efficacy and safety data in heavily pretreated patients with ovarian cancer and non-small cell lung cancer (NSCLC) adenocarcinoma. These data showed that XMT-1536 was generally well tolerated at doses up to 43 mg/m2 and induced confirmed responses and durable stable disease in both ovarian cancer and NSCLC adenocarcinoma with a favorable trend towards higher response rates in patients with higher NaPi2b expression. As disclosed in its conference call on March 30, 2020, the Company has established 43 mg/m2 as the maximum tolerated dose and the dose escalation portion of the study is no longer enrolling patients.

·XMT-1536 Phase 1 interim expansion abstract accepted for poster session at upcoming ASCO (Free ASCO Whitepaper) 2020 virtual scientific program. Mersana plans to present interim data from the ongoing expansion on a live conference call and webcast featuring study investigator, Debra L. Richardson, MD, Associate Professor of Gynecologic Oncology at the Stephenson Cancer Center at the University of Oklahoma Health Sciences Center and the Sarah Cannon Research Institute, on Wednesday, May 27, 2020 at 8:00 a.m. ET and at the upcoming ASCO (Free ASCO Whitepaper) virtual scientific program scheduled for May 29 – 31, 2020. These data will include safety, tolerability and efficacy for patients treated with 36 mg/m2 and 43 mg/m2. Further, these interim data will also report on the current status of the relationship between response and biomarker expression. With a cutoff of May 1, 2020, the ASCO (Free ASCO Whitepaper) presentation will include 20 RECIST-evaluable ovarian cancer patients and 4 RECIST-evaluable NSCLC patients. Biomarker expression data will be available for the majority of evaluable patients. Additional patients are enrolled in the study but have not yet reached the RECIST evaluation timepoint. Study sites continue to enroll, and patients continue to be monitored under FDA-recommended mitigation strategies for COVID-19.

·Second clinical candidate, XMT-1592, a Dolasynthen ADC targeting NaPi2b, remains on track to enter the clinic in the second quarter of 2020. In preclinical studies, XMT-1592 has shown four times greater efficacy in a patient-derived lung tumor model in comparison to Dolaflexin, a platform that has already shown success when targeted to NaPi2b. The Phase 1 study will seek to clinically validate the differentiation of XMT-1592 by using the Company’s NaPi2b experience to efficiently progress this candidate through dose escalation. The Company plans to present XMT-1592 preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting scheduled for June 22 – 24, 2020.

Discovery & Platform Progress

·First-in-class ADC targeting B7-H4 on track for candidate selection in the second half of 2020. B7-H4 is expressed on both tumor cells and immunosuppressive tumor-associated macrophages (TAMs). This provides the potential for both a direct, cytotoxic antitumor effect as well as for additional payload delivery to the tumor microenvironment that can further contribute to immunogenic cell death, dendritic cell activation and stimulation of an immune response consistent with the features of the Company’s unique DolaLock payload. IND-enabling studies are ongoing, and the Company plans to disclose its development candidate and supporting data in the second half of 2020.

·Disclosure of the first Immunosynthen development candidate on track for the second half of 2020. Immunosynthen, the Company’s novel STING-agonist ADC platform, has generated preclinical data across multiple targets and models showing complete regression of tumors in vivo with a single, well-tolerated dose, consistent with increased cytokine expression and immune cell infiltration within the tumor, and immune memory. The Company plans to present additional preclinical data at the upcoming virtual AACR (Free AACR Whitepaper) annual meeting in June 2020 and expects to select its first Immunosynthen development candidate in the second half of 2020.

Corporate

·New addition to Board to Directors. In April 2020, the Company announced the appointment of Martin H. Huber, M.D., to its Board of Directors. Dr. Huber is the Chief Medical Officer of Xilio Therapeutics. Prior to that, he served as Senior Vice President and Chief Medical Officer at TESARO, Inc.

·Raised $65M in gross proceeds from ATM facility. On April 7, 2020, Mersana announced that it raised gross proceeds of approximately $65 million through its At-the-Market (ATM) facility with participation based on interest received from Avoro Capital Advisors LLC, Bain Capital Life Sciences, Consonance Capital Investors and David Mott, Mersana’s Chairman of the Board.

Response to COVID-19 and Potential Business Impacts

Mersana continues to monitor the impact of the COVID-19 pandemic on operations and ongoing clinical and preclinical development, as well as discovery efforts. Mitigation activities to minimize COVID-19-related operation disruptions are ongoing and include:

·In line with guidance from the U.S. Centers for Disease Control and Prevention (CDC) and the state of Massachusetts, the Company has implemented work from home measures for all non-laboratory employees and has suspended all business travel. The Company has also prioritized laboratory activities and implemented staggered schedules in the interest of safety and efficiency for laboratory-based employees.

·The Company currently works with over 20 investigational sites in different geographic areas across the United States which are enrolling patients in the XMT-1536 Phase 1 study. Consistent with FDA guidance, the Company issued an administrative letter to allow for remote patient monitoring and remote testing, when possible. Most of the study sites continue to enroll patients in the study. At this time and subject to further COVID-19 implications to patient enrollment, the Company expects to be able to present more mature data from the expansion portion of the study in the second half of 2020.

·Mersana believes it has sufficient inventory of XMT-1536 and XMT-1592 to support its ongoing and planned clinical studies as well as sufficient inventory of advanced intermediates stockpiled in the United States to support more than two years of manufacturing of drug substance and product. At this time and subject to further COVID-19 implications, the Company does not anticipate any disruptions to its clinical supply.

Upcoming Events

·The Company will present interim data from the XMT-1536 Phase 1 expansion study on a live conference call and webcast on Wednesday, May 27, 2020 at 8 a.m. ET and during a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program scheduled for May 29 – 31, 2020.

·Mersana will give a corporate presentation at the Virtual Jefferies Healthcare Conference scheduled for June 2 – 4, 2020.
·Mersana will present preclinical data for XMT-1592 and its novel Immunosynthen STING-agonist ADC platform at the AACR (Free AACR Whitepaper) Virtual Annual Meeting scheduled for June 22 – 24, 2020.

First Quarter 2020 Financial Results

Cash, cash equivalents and marketable securities as of March 31, 2020, were $78.4 million, compared to $99.8 million as of December 31, 2019. Net cash used in operating activities in the first quarter of 2020 was $21.2 million compared to $24.7 million for the same period in 2019. Net cash used in operating activities increased in the first quarter of 2020 compared to $12.6 million in the fourth quarter of 2019 due to the timing of compensation payments and a reduction of the accounts payable balance.

On April 7, 2020 the Company raised approximately $65.0 million in gross proceeds through the sale of approximately 8.9 million shares of common stock at a purchase price of $5.59 and another 2.0 million shares at the closing price of $7.74, in each case the market price at the time of sale, through its At-the-Market (ATM) facility. In addition, the Company has the option to draw additional funds of up to $15.0 million through the existing debt financing agreement with Silicon Valley Bank. The Company expects that its current cash, cash equivalents and marketable securities, including the $65.0 million of gross proceeds from the ATM facility, will enable it to fund its operating plan into early 2022.

·Collaboration revenue for the first quarter of 2020 was immaterial, compared to $41.0 million for the same period in 2019. The decrease in collaboration revenue was primarily as a result of the $40.0 million in deferred revenue that was recognized in the first quarter of 2019 associated with the discontinuation of the partnership with Takeda announced in January 2019.
·Research and development expenses for the first quarter of 2020 were approximately $12.2 million, compared to $15.1 million for the same period in 2019. The difference was primarily due to an upfront payment for a technology license fee and timing of research efforts, a decrease in expenditures in support of partner programs, and decreased manufacturing costs for XMT-1536 and XMT-1522, offset by increased costs for XMT-1536 clinical expenses, and advancement of companion diagnostics development efforts for the NaPi2b biomarker.
·General and administrative expenses for the first quarter of 2020 were approximately $4.9 million, compared to $4.4 million during the same period in 2019.
·Net loss for the first quarter of 2020 was $16.9 million, or $0.35 per share, compared to a net income of $21.9 million, or $0.72 per share, for the same period in 2019. The difference year over year was primarily attributable to $40.0 million in deferred revenue that was recognized in the first quarter of 2019 as a result of the discontinuation of Takeda partnership announced in January 2019. Weighted average common shares outstanding for the quarters ended March 31, 2020 and March 31, 2019, were 47,988,630 and 30,299,650, respectively. Common shares outstanding as of May 5, 2020 were 58,949,470, inclusive of the impact of the ATM transaction and the exercise of pre-funded warrants by Biotechnology Value Fund, L.P. pursuant to the exchange agreement entered into in November 2019.

Conference Call Details

Mersana Therapeutics will host a conference call and webcast today at 8:00 a.m. ET to report financial results for the first quarter of 2020 and provide certain business updates. To access the call, please dial 877-303-9226 (domestic) or 409-981-0870 (international) and provide the Conference ID 9961647. A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com.

On May 8, 2020 ThermoGenesis Holdings, Inc. (Nasdaq: THMO), a market leader in automated cell processing tools and services in the cell and gene therapy field, reported that the Company will release its financial results for the first quarter ended March 31, 2020 and provide a corporate strategic update on Thursday, May 14, 2020 after the close of trading (Press release, Thermogenesis, MAY 8, 2020, View Source [SID1234557402]). A conference call and webcast will follow at 1:30 p.m. PT/ 4:30 p.m. ET.

Schedule your 30 min Free 1stOncology Demo!
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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!

To participate in the conference call, please dial 1-844-889-4331 (domestic), 1-412-380-7406 (international) or 1-866-605-3852 (Canada). To access a live webcast of the call, please visit: View Source

A replay of the call will be available until June 4 and can be accessed by dialing 1-877-344-7529 (domestic), 1-412-317-0088 (international) or 1-855-669-9658 (Canada) and referencing access code 10142864. The webcast will be available for three months.

On May 8, 2020 Eli Lilly and Company (NYSE: LLY) reported that the U.S. Food and Drug Administration (FDA) approved Retevmo (selpercatinib, 40 mg & 80 mg capsules), the first therapy specifically indicated for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), and the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) (Press release, Eli Lilly, MAY 8, 2020, View Source [SID1234557428]). Retevmo was approved under the FDA’s Accelerated Approval regulations based on the LIBRETTO-001 Phase 1/2 trial’s endpoints of objective response rate (ORR) and duration of response (DoR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

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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

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Retevmo is a selective RET kinase inhibitor. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. Retevmo is an oral prescription medicine, 120 mg or 160 mg based on weight, taken twice daily until disease progression or unacceptable toxicity.1

"In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases," said Alexander Drilon, M.D., acting chief of early drug development at Memorial Sloan Kettering Cancer Center and lead investigator for LIBRETTO-001. "The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy. I am pleased that patients with these RET-driven cancers have this newly approved option."

Retevmo was evaluated in the single-arm, multi-center Phase 1/2 LIBRETTO-001 trial, the largest trial (N=702) of patients with RET-driven cancers. The trial enrolled both treatment-naive patients and heavily pretreated patients with a variety of advanced solid tumors including RET fusion-positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer, and certain other solid tumors with RET alterations. Major efficacy outcomes were ORR and DoR, assessed by a blinded independent review committee. Prespecified secondary endpoints included central nervous system (CNS) ORR and CNS DoR.

RET Fusion-Positive
NSCLC

RET-Mutant MTC

RET Fusion-Positive Thyroid
Cancers

Systemic
Treatment
Naïve

Treatment
Experienced

Cabozantinib
/Vandetanib
Naïve

Cabozantinib
/Vandetanib
Experienced

Systemic
Treatment
Naïve

Treatment
Experienced

No. of patients

39

105

88

55

8

19

ORR (95% CI)

85 (70, 94)

64 (54, 73)

73 (62, 82)

69 (55, 81)

100 (63, 100)

79 (54, 94)

Median DoR,
months (95% CI)

NR (12, NR)

17.5 (12, NR)

22 (NR, NR)

NR (19.1, NR)

NR (NR, NR)

18.4 (7.6, NR)

NR=Not Reached

Thyroid cancers include: papillary, Hurthle cell, anaplastic, and poorly differentiated

Up to 50 percent of patients with RET fusion-positive NSCLCs can have tumors that metastasize to the brain.2 Among previously treated NSCLC patients with measurable brain metastases, 10 out of 11 patients observed intracranial responses (CNS ORR), with all 10 patients experiencing a CNS DoR of greater than or equal to six months.

The labeling for Retevmo contains warnings and precautions for hepatotoxicity (evidence of liver dysfunction), hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, and embryo-fetal toxicity.

In the LIBRETTO-001 trial, there was a five percent discontinuation rate due to adverse reactions (ARs). The most common ARs, including laboratory abnormalities, (≥25 percent) were increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema (swelling in the arms or legs), decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation. In addition, the most frequent serious AR (≥ 2 percent) was pneumonia.

See Important Safety Information below and full Prescribing Information for additional information, including dosing modifications.

"RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers. For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET," said Lori J. Wirth, M.D., medical director of head and neck cancers, Massachusetts General Hospital Cancer Center. "Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option."

"We are extremely proud of how quickly the combined Loxo Oncology and Lilly Oncology teams brought Retevmo to patients, further demonstrating our commitment to delivering life-changing medicines to people living with cancer," said Anne White, president of Lilly Oncology. "Retevmo entered clinical trials in May of 2017 and is now approved less than three years later, representing the most rapid timeline in the development of an oncology medicine with multiple indications. We applaud the FDA for their leadership and collaboration, recognizing the importance of bringing a new therapy to patients with advanced or metastatic RET-driven lung and thyroid cancers."

Retevmo should only be used in advanced or metastatic patients whose tumors have a RET fusion in NSCLC or thyroid cancer or a RET mutation in MTC. This can be determined through biomarker testing. Next-generation sequencing (NGS), either with tumor tissue biopsy or liquid biopsy, can be an appropriate biomarker test to determine actionable genomic alterations, including RET. If NGS is not available, RET can be detected using other biomarker testing methods. An FDA-approved test for the detection of RET fusions and RET mutations is not currently available. In LIBRETTO-001, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using NGS, PCR, or FISH. Immunohistochemistry was not used in the clinical trial.

"Increasingly, through the use of comprehensive biomarker testing, patients with metastatic cancer have an opportunity to receive a treatment tailored to the specific genomic nature of their tumor," said Andrea Ferris, president and chief executive officer at LUNGevity. "Retevmo represents an important new advance in this growing field, as the first therapy approved specifically for patients with RET-driven tumors. We urge patients to ask their doctors about broad biomarker tests that include RET alterations."

Retevmo was granted orphan drug designation by the FDA for the treatment of RET fusion-positive NSCLC and for the treatment of RET fusion-positive and RET-mutant thyroid cancers including poorly differentiated thyroid cancer, undifferentiated or anaplastic thyroid cancer, MTC and locally advanced or metastatic follicular or papillary thyroid cancer. The two confirmatory Phase 3 trials (LIBRETTO-431 and LIBRETTO-531) are currently enrolling patients.

Retevmo is expected to be available from specialty pharmacies within one week.

Click here to view the metastatic RET fusion-positive NSCLC fact sheet.

Click here to view the advanced RET-driven thyroid cancers fact sheet.

Click here to view the broad panel biomarker testing fact sheet.

Click here to view the Retevmo product fact sheet.

Click here to view the Retevmo product photo.

Click here to view the Retevmo logo.

Visit retevmo.com for more information.

About Retevmo (selpercatinib)

Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced reh-TEHV-moh) is a selective and potent RET kinase inhibitor. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. Retevmo is an oral prescription medicine, 120 mg or 160 mg dependent on weight (-/+ 50 kg), taken twice daily until disease progression or unacceptable toxicity.3

About RET-Driven Cancers
Genomic alterations in the RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2 percent of NSCLC; and 10-20 percent of papillary, Hurthle cell, anaplastic, and poorly differentiated thyroid cancers. Activating RET point mutations account for approximately 60 percent of sporadic MTC and approximately 90 percent of germline MTC. RET fusion-positive cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers.

About LIBRETTO-001
The LIBRETTO-001 Phase 1/2 trial was the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor. The trial included a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). The Phase 2 portion of the trial had major efficacy outcomes of ORR and DoR, and prespecified secondary endpoints of CNS ORR and CNS DoR, as determined by an independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Results from the NSCLC population were last presented at the 2019 IASLC World Congress on Lung Cancer (WCLC), while results from the thyroid populations were last presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress.

Important Safety Information for Retevmo (selpercatinib)

Hepatotoxicity: Serious hepatic adverse reactions occurred in 2.6% of patients treated with Retevmo. Increased AST occurred in 51% of patients, including Grade 3 or 4 events in 8% and increased ALT occurred in 45% of patients, including Grade 3 or 4 events in 9%. The median time to first onset for increased AST was 4.1 weeks (range: 5 days to 2 years) and increased ALT was 4.1 weeks (range: 6 days to 1.5 years). Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue Retevmo based on the severity.

Hypertension occurred in 35% of patients, including Grade 3 hypertension in 17% and Grade 4 in one (0.1%) patient. Overall, 4.6% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity.

Retevmo can cause concentration-dependent QT interval prolongation. An increase in QTcF interval to >500 ms was measured in 6% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 15% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes and TSH at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity.

Serious, including fatal, hemorrhagic events can occur with Retevmo. Grade ≥ 3 hemorrhagic events occurred in 2.3% of patients treated with Retevmo including 3 (0.4%) patients with fatal hemorrhagic events, including one case each of cerebral hemorrhage, tracheostomy site hemorrhage, and hemoptysis. Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage.

Hypersensitivity occurred in 4.3% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.6%. The median time to onset was 1.7 weeks (range 6 days to 1.5 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg. Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity.

Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established.

Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for at least 1 week after the final dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the final dose.

Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-001, were hypertension (18%), prolonged QT interval (4%), diarrhea (3.4%), dyspnea (2.3%), fatigue (2%), abdominal pain (1.9%), hemorrhage (1.9%), headache (1.4%), rash (0.7%), constipation (0.6%), nausea (0.6%), vomiting (0.3%), and edema (0.3%).

Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-001, were dry mouth (39%), diarrhea (37%), hypertension (35%), fatigue (35%), edema (33%), rash (27%), constipation (25%), nausea (23%), abdominal pain (23%), headache (23%), cough (18%), prolonged QT interval (17%), dyspnea (16%), vomiting (15%), and hemorrhage (15%).

Laboratory abnormalities (all grades; Grade 3-4) ≥20% worsening from baseline in patients who received Retevmo in LIBRETTO-001, were AST increased (51%; 8%), ALT increased (45%; 9%), increased glucose (44%; 2.2%), decreased leukocytes (43%; 1.6%), decreased albumin (42%; 0.7%), decreased calcium (41%; 3.8%), increased creatinine (37%; 1.0%), increased alkaline phosphatase (36%; 2.3%), decreased platelets (33%; 2.7%), increased total cholesterol (31%; 0.1%), decreased sodium (27%; 7%), decreased magnesium (24%; 0.6%), increased potassium (24%; 1.2%), increased bilirubin (23%; 2.0%), and decreased glucose (22%; 0.7%).

Concomitant use of acid-reducing agents decrease selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid).

Concomitant use of strong and moderate CYP3A inhibitors increase selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently.

Concomitant use of strong and moderate CYP3A inducers decrease selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers.

Concomitant use of Retevmo with CYP2C8 and CYP3A substrates increase their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling.

The safety and effectiveness of Retevmo have not been established in pediatric patients less than 12 years of age. The safety and effectiveness of Retevmo have been established in pediatric patients aged 12 years and older for medullary thyroid cancer (MTC) who require systemic therapy and for advanced RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate). Use of Retevmo for these indications is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients aged 12 years and older.

No dosage modification is recommended for patients with mild to moderate renal impairment (creatinine clearance [CLcr] ≥30 mL/Min, estimated by Cockcroft-Gault). A recommended dosage has not been established for patients with severe renal impairment or end-stage renal disease.

Reduce the dose when administering Retevmo to patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times upper limit of normal [ULN] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment.

Please see full Prescribing Information and Patient Prescribing Information for Retevmo.

SE HCP ISI All_08MAY2020

About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly’s commitment to people with cancer, please visit www.LillyOncology.com.