On June 27, 2022 Bonnie J Addario Lung Cancer Foundation reported that Targeted therapy research was front and center at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Bonnie J Addario Lung Cancer Foundation, JUN 27, 2022, View Source [SID1234616288]). Data was presented from several studies detailing new targeted therapies and better understanding of how to treat non-small cell lung cancer (NSCLC) with various driver mutations . Following are some highlights from targeted therapy information presented at the meeting.

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KRAS
The first targeted therapy for NSCLC with a KRAS G12C mutation, Lumakras (sotorasib), was approved last year as an option for NSCLC that had already been treated with another therapy, such as chemotherapy. Although this was a breakthrough in making targeted therapy available for one of the most common NSCLC mutations, only a portion of KRAS G12C-positive NSCLC responded well to Lumakras (sotorasib) and identifying new treatment options will be beneficial to many patients.

Data from the KRYSTAL-1 trial showed that the newer KRAS G12C targeted therapy, adagrasib, led to promising rates and lengths of response when given as a treatment after other previous therapies. A larger clinical trial, KRYSTAL-12, is in progress to compare adagrasib to standard therapies. Positive results may lead to adabrasib being an additional targeted therapy option for KRAS G12C-positive NSCLC.
Data presented from the KRYSTAL-1 trial showed that adagrasib had promising results when treating brain metastasis. Importantly, data on the effectiveness of adagrasib for active and untreated brain metastasis was shared. This research is important since patients with this type of brain metastasis are often prevented from participating in clinical trials.
EGFR
Tagrisso (osimertinib)’s effectiveness has made it the standard of care first treatment for EGFR-positive NSCLC. But for many patients, resistance (where the cancer starts to grow or spread again while still being treated) is an issue. More treatment options are needed for EGFR-positive patients to help when Tagrisso (osimertinib) resistance happens.

Updated data was shared from the CHRYSALIS-2 trial, confirming that a combination of amivantamab and azertinib produced promising results in treating EGFR-positive NSCLC, even after progression on multiple other lines of therapy including Tagrisso (osimertinib). This combination is being compared to other therapies in larger clinical trials and may have promise as a future option.
Data from an early phase trial showed that telisotuzumab vedotin (Teliso-V), showed initial positive results in treating NSCLC that had c-MET overexpression after developing Tagrisso (osimertinib) resistance. Repeat biomarker testing (after resistance to targeted therapies occurs) may help identify new changes such as c-MET overexpression for which clinical trials may be an option.
EGFR-positive NSCLC with an exon 20 mutation does not respond as well to standard targeted therapies approved to treat NSCLC with the most common EGFR mutations. Specific targeted therapies for EGFR exon 20-positive NSCLC, Exkivity (mobocertinib) and Rybrevant (amivantamab-vmjw), were approved in 2021, but these drugs do not produce responses to the same degree as the other EGFR targeted therapies. Many people living with EGFR exon 20-positive NSCLC would benefit from additional treatment options.

A clinical trial of CLN-081 showed promising responses that occurred when it was used to treat NSCLC with an EGFR exon 20 mutation that had already been treated previously with multiple other therapies, including other EGFR targeted therapies. It may represent a future additional option for patients with NSCLC with an EGFR exon 20 mutation.
MET
Since 2020, two different targeted therapies have been approved for initial treatment of NSCLC with a MET exon 14 skipping mutation—Tabrecta (capmatinib) and Tepmetko (tepotinib). However, as with many targeted therapies, some tumors may not respond well to these drugs and resistance can develop. This underscores the need to continue researching new treatments for NSCLC with these mutations.

Data from the CHRYSALIS-2 trial revealed that amivantimab may be a future addition treatment option for NSCLC with a MET exon 14 skipping mutation. It showed promising rates and durations of responses, however the effectiveness may be higher for cancer that has not yet been treated with other MET exon 14 targeted therapies.
NTRK
Vitrakvi (larotrectinib) and Rozlytrek (entrectinib) are both approved initial targeted therapy options for cancers that have an NTRK fusion, including NSCLC. Understanding how well these drugs work long term for patients and under which situations they are most effective could help determine the best options for NTRK fusion-positive NSCLC.

Combined long-term follow-up data from two different clinical trials confirmed that Vitrakivi (larotrectinib) produces high rates of lasting response to treatment in NTRK fusion-positive NSCLC, even in patients with brain metastasis. Weight gain was noted as a physical side effect for a group of patients.
Biomarker Testing
Receiving comprehensive biomarker testing is important at diagnosis to determine if a NSCLC tumor has a mutation that would benefit from a targeted therapy. It is also beneficial at progression after being on targeted therapy to help pick the next best treatment option. Biomarker testing is often done using a tumor biopsy, however a liquid biopsy (simple blood sample) can be helpful when getting a tumor biopsy is difficult or does not work well. Understanding how biomarker testing using tissue biopsies and liquid biopsies compare can help inform treatment decisions-based on these different types of tests.

Data from the BFAST trial, a study looking to see if using only liquid biopsy biomarker testing would help identify ROS1-positive NSCLC that would benefit from the ROS-1 targeted therapy Rozlytrek (entrectinib), was shared. Researchers observed that overall, patients had slightly lower benefit from Rozlytrek (entrectinib) in this trial than expected. However, researchers believe that liquid biopsy is more likely to detect a mutation when the cancer is at a more advanced stage and thus patients in this trial had less benefit from therapy since they had more advanced cancer growth. This may indicate that tumor biopsy-based testing is better at diagnosis or with lower stage cancer and liquid biopsy may be best for repeat testing at progression or with higher stage cancer.

On June 27, 2022 Cepheid and BioGX reported a collaboration between the two companies to deliver a PCR test for Monkeypox that will run on the GeneXpert system (Press release, Cepheid, JUN 27, 2022, View Source [SID1234616287]). With a global installed base of over 40,000 GeneXpert systems in 180 countries, this test could be deployed quickly in multiple settings where actionable information is needed .

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According to the Centers for Disease Control and Prevention (CDC), monkeypox is rare and does not spread easily between people without close contact. While the threat of monkeypox to the general U.S. population remains low1, it is important for healthcare providers worldwide to have a preparedness plan. One of the key signs of infection with the virus is fever with development of a maculopapular rash, often appearing as small, raised spots. However, there are many other illnesses, such as chickenpox, measles, bacterial skin infections, syphilis, herpes, and medication-associated allergies that can present with similar symptoms. This underscores the need for a molecular test that can identify monkeypox. The World Health Organization recommends PCR as the preferred laboratory test for monkeypox, using an appropriate skin lesion sample2.

"Our FleXible Cartridge program gives Cepheid the ability to work with external partners to develop accurate tests quickly when the need arises," said David H. Persing, M.D., Ph.D., Cepheid’s EVP and Chief Scientific Officer. Beginning with Bacillus anthracis (Anthrax) and continuing with Mycobacterium tuberculosis, Influenza H1N1, Ebola virus and SARS-CoV-2 among others, Cepheid has a long history of quickly developing and delivering tests that address urgent public health issues as they emerge."

BioGX also has a successful track record of working with government agencies and diagnostic partners to quickly develop and manufacture at-scale molecular tests for detection of emerging pathogens.

"We previously collaborated on a project with the CDC to develop and manufacture a multiplex Monkeypox/Orthopoxvirus test for a GeneXpert-based study3, and now with Cepheid we are moving to the validation stage utilizing the FleXible cartridge," said Michael Vickery, Ph.D., BioGX’s EVP and Chief Scientific Officer. "Regional response teams need a PCR test that is fast and easy to implement when they suspect an outbreak due to a novel pathogen."

Product in development. Not for use in diagnostic procedures. Not reviewed by any regulatory body. Product in development is subject to change and specifications have not yet been established.

On June 27, 2022 AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of LYNPARZA for the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy (Press release, Merck & Co, JUN 27, 2022, View Source [SID1234616286]).

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The CHMP based its positive opinion on results from the Phase 3 OlympiA trial presented during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and published in The New England Journal of Medicine in June 2021.

Breast cancer is the most commonly diagnosed cancer worldwide, with an estimated 2.3 million patients diagnosed in 2020. In the European Union (EU), one in seven people who were assigned female at birth will develop breast cancer in their lifetime. Approximately 75% of breast cancer patients worldwide are diagnosed with early breast cancer; however, a quarter of these patients will experience disease recurrence following surgery. In Europe, germline BRCA mutations are found in approximately 9% of patients.

Professor Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor of Oncology at The Institute of Cancer Research, London and King’s College London, said: "For patients with high-risk, early-stage breast cancer, the risk of recurrence remains unacceptably high, and cancer will return for more than one in four of these patients. Today’s recommendation is hopeful news for patients in Europe, as we move closer to setting a potential new standard of care that improves overall survival in patients suitable for treatment with olaparib."

Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said, "If approved, LYNPARZA will provide a new targeted treatment option for patients with germline BRCA-mutated, HER2-negative early breast cancer in Europe. By treating patients as early as possible in their disease, we hope to avoid life-threatening recurrence and give people more time with their loved ones."

Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said, "Patients with germline BRCA-mutated, HER2-negative early breast cancer will often develop breast cancer at an earlier age than those without BRCA mutations, impacting people in their prime. Today’s positive opinion brings us closer to our goal of offering a much-needed new treatment option to these patients in Europe."

In the trial, LYNPARZA demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of invasive disease-free survival (IDFS), reducing the risk of invasive breast cancer recurrences, second cancers or death by 42% (HR=0.58 [99.5% CI, 0.41-0.82]; p<0.0001) versus placebo. Overall survival (OS) data presented in March 2022 at the European Society for Medical Oncology Virtual Plenary showed LYNPARZA demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of OS, reducing the risk of death by 32% (HR=0.68; 98.5% CI 0.47-0.97; p=0.0091) versus placebo. The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials. The most common adverse reactions (ARs) ≥10% for LYNPARZA were nausea (57%), fatigue (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%) and stomatitis (10%). Approximately 10% of patients who received LYNPARZA discontinued treatment due to an AR. The most common Grade ≥3 ARs for LYNPARZA were anemia (9%), neutropenia (5%), leukopenia (3%) and fatigue (1.8%). The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials. The most common adverse reactions (ARs) ≥10% for LYNPARZA were nausea (57%), fatigue (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%) and stomatitis (10%). Approximately 10% of patients who received LYNPARZA discontinued treatment due to an AR. The most common Grade ≥3 ARs for LYNPARZA were anemia (9%), neutropenia (5%), leukopenia (3%) and fatigue (1.8%).

In March 2022, LYNPARZA was approved in the U.S. for the adjuvant treatment of patients with gBRCAm, HER2-negative high-risk early breast based on results from the OlympiA trial. LYNPARZA is also approved in the U.S., EU, Japan and several other countries for the treatment of adult patients with gBRCAm, HER2-negative metastatic breast cancer previously treated with chemotherapy and, if hormone receptor-positive, endocrine therapy if appropriate based on results from the Phase 3 OlympiAD trial. In the EU and Japan, this indication also includes patients with locally advanced breast cancer.

About OlympiA
OlympiA is a Phase 3, double-blind, parallel-group, placebo-controlled, international trial evaluating the efficacy and safety of LYNPARZA versus placebo as adjuvant treatment in patients with gBRCAm, HER2-negative high-risk early breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. The primary endpoint is IDFS, defined as the time from randomization to the date of the first loco-regional or distant recurrence or new cancer or death from any cause. A key secondary efficacy outcome measure is OS.

The OlympiA trial is led by BIG in partnership with the Frontier Science & Technology Research Foundation, NRG Oncology, AstraZeneca and Merck.

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 breast cancer
Early breast cancer is defined as disease confined to the breast with or without regional lymph node involvement and the absence of distant metastatic disease. For women in the U.S., the five-year survival is 99% for localized breast cancer (cancer that is found only in the breast area) and 86% for regional breast cancer (cancer that has spread outside the breast to nearby structures or lymph nodes). Breast cancer is one of the most biologically diverse tumor types with various factors fueling its development and progression. The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.

About BRCA mutations
BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

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.

On June 27, 2022 Philogen reported that it will be Bronze Sponsor of the Post-Chicago Meeting in Münich (30-1 July) (Presentation, Philogen, JUN 27, 2022, View Source [SID1234616284]).

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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

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Philogen will chair a Satellite Symposium on Friday July 1, 11.30-12.00 am. Dr. Alfredo Covelli, Philogen’s CMO, will give a presentation entitled "Immunocytokines for the therapy of cancer: the Philogen Portfolio".

On June 27, 2022 Philogen reported that it will attend the 3rd Annual Cytokine-Based Drug Development Summit in Boston (Presentation, Philogen, JUN 27, 2022, View Source [SID1234616283]).

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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

                  Schedule Your 30 min Free Demo!

Roberto De Luca, Head of Antibody Therapeutics, will give a virtual lecture entitled "Antibody-cytokine fusion proteins against Fibroblast Activation Protein (FAP)" on the 28 of July.