On December 10, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) reported new data from the Phase 3 ASCENT study evaluating Trodelvy (sacituzumab govitecan-hziy) in relapsed or refractory metastatic triple-negative breast cancer (TNBC) who received two or more prior systemic therapies, at least one of them for metastatic disease (Press release, Gilead Sciences, DEC 10, 2021, View Source [SID1234596773]). In this subgroup analysis of Black patients, Trodelvy improved progression-free survival (PFS), with a 56% reduction in the risk of disease worsening or death (HR: 0.44; 95% CI: 0.24-0.80; P=0.008) and a median PFS of 5.4 months (n=28) versus 2.2 months with chemotherapy (n=34). Trodelvy also extended median overall survival to 13.8 months versus 8.5 months with physician’s choice of chemotherapy (HR: 0.64; 95% CI: 0.34-1.19; P=0.159). The results were presented at the 2021 San Antonio Breast Cancer Symposium (SABCS) (Poster #P5-16-07).

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"Black women are almost three times more likely to be diagnosed with TNBC and may experience worse clinical outcomes compared with white women," said Lisa Carey, MD, Medical Director of the UNC Breast Center, the Physician-in-Chief of the North Carolina Cancer Hospital and Associate Director of Clinical Research at UNC Lineberger Comprehensive Cancer Center. "This inequality is driven by comorbidities, differences in TNBC biology and other health disparities, which is why understanding how sacituzumab govitecan can work in these patients is so critical. This analysis of the Phase 3 ASCENT study confirms that sacituzumab govitecan delivered the same clinical benefit for Black women as the overall population in second-line locally advanced or metastatic TNBC."

TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. It is more frequently diagnosed in younger and premenopausal women and is more prevalent in Black and Hispanic women. Black women have three times the risk of TNBC as white women, and a 42% higher mortality rate from breast cancer overall. The five-year survival rate for this sub-type of breast cancer is 12%, compared with 28% for other breast cancer types, and these poor outcomes are often coupled with a significant decrease in quality of life, especially in relapsed/refractory disease.

Additionally, Trodelvy demonstrated a higher overall response rate (32% versus 6%) and clinical benefit rate (43% versus 15%) compared with physician’s choice of chemotherapy in this subgroup. Efficacy and safety results from this subgroup were consistent with those observed in the overall ASCENT study population.

The most frequent Grade ≥3 treatment-related adverse reactions for Trodelvy compared to chemotherapy were neutropenia (48% versus 42%), anemia (12% versus 6%), leukopenia (8% versus 16%), and febrile neutropenia (8% versus 3%). In this subgroup, no patients in the Trodelvy arm and one patient in the chemotherapy arm discontinued treatment due to adverse reactions. There were no treatment-related deaths with Trodelvy in this subgroup. The Trodelvy U.S. Prescribing Information has a BOXED WARNING for severe or life-threatening neutropenia and severe diarrhea; see below for Important Safety Information.

"Black women with TNBC have historically faced a poorer prognosis compared to white women," said Bill Grossman, MD, PhD, Senior Vice President, Oncology Clinical Research, Gilead Sciences. "Gilead is committed to the continued advancement of transformational science for those impacted by cancer, and we are pleased this analysis affirms consistent clinical outcomes with Trodelvy for Black women in second-line metastatic TNBC."

About the ASCENT Study

The ASCENT study is a global, open-label, randomized Phase 3 study that enrolled more than 500 patients across 230 study locations. The study evaluated the efficacy and safety of Trodelvy compared with a single-agent chemotherapy of the physician’s choice in patients with unresectable, locally advanced or metastatic TNBC who had received at least two prior systemic treatments. Patients were randomized to receive either Trodelvy or a chemotherapy chosen by the patients’ treating physicians. The primary endpoint was progression-free survival (PFS, as determined by blinded independent central review) in patients without brain metastases. Secondary endpoints included: PFS for full study population or intention-to-treat (ITT) population, overall survival in both the ITT population and in the subgroup without brain metastasis, independently determined objective response rate, duration of response, time to onset of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), quality of life and safety. More information about ASCENT is available at View Source

About Trodelvy

Trodelvy is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein overexpressed in multiple types of epithelial tumors, including metastatic TNBC and metastatic urothelial cancer (UC), where high expression is associated with poor survival and relapse. Trodelvy is approved for adults with metastatic TNBC in the United States, the European Union, Australia, Canada, Great Britain and Switzerland. Trodelvy is also under multiple regulatory reviews worldwide, including in Singapore and China through our partner Everest Medicines. Trodelvy continues to be developed for potential use in other TNBC and metastatic UC populations and is also being developed as an investigational treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.

In the United States, Trodelvy is indicated for the treatment of:

Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic UC who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.
U.S. Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 61% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 7%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever.

Diarrhea: Diarrhea occurred in 65% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation following diarrhea. Neutropenic colitis occurred in 0.5% of patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.3%. The incidence of anaphylactic reactions was 0.3%. Pre-infusion medication is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 66% of all patients treated with Trodelvy and Grade 3 nausea occurred in 4% of these patients. Vomiting occurred in 39% of patients and Grade 3-4 vomiting occurred in 3% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 67% in patients homozygous for the UGT1A1*28, 46% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 25% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 11% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were fatigue, neutropenia, diarrhea, nausea, alopecia, anemia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPHY study (IMMU-132-06), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, neutropenia, nausea, any infection, alopecia, anemia, decreased appetite, constipation, vomiting, abdominal pain, and rash. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

On December 10, 2021 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, reported a presentation at the Antibody Engineering & Therapeutics Conference which is being held December 12 – 16, 2021 in San Diego, CA, and virtually (Press release, aTyr Pharma, DEC 10, 2021, View Source [SID1234596772]).

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The presentation will discuss the practical utility of repertoire data for antibody affinity maturation, including clonal grouping of sequencing data with lead candidates to understand likely maturation pathways and partially mature antibodies with minimal effort, complementing existing methods. aTyr’s tRNA synthetase biology platform is focused on elucidating novel pathways mediated through extracellular response and creating new biologics to modulate these pathways, by either developing protein therapies based on extracellular tRNA synthetase fragments or generating monoclonal antibodies to target the pathway. Engineering techniques that enhance the affinity and selectivity of antibodies can accelerate the development of antibody therapeutics against novel targets.

Details of the presentation are as follows:

Title: Practical Utility of Repertoire Data for Antibody Affinity Maturation
Presenter: Luke Burman, Senior Scientist. aTyr Pharma, San Diego, CA.
Session: Workshop B: When High Affinity is Necessary in Antibody Therapeutics
Date: Sunday, December 12, 2021
Time: 2:15pm PST / 5:15pm EST

"We are excited to present on this novel approach that highlights aTyr’s cutting-edge, in-house antibody engineering techniques," said Leslie Nangle, Ph.D., Vice President, Research at aTyr. "These methods have broad applicability for aTyr’s tRNA synthetase platform and present an opportunity to support the expansion of our pipeline with enabling technology that accelerates the development of antibody candidates with high affinity and selectivity for their receptor targets."

On December 10, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported clinical data on zenocutuzumab (Zeno) in combination with trastuzumab and vinorelbine in patients (pts) with HER2 positive/amplified (HER2+) metastatic breast cancer (MBC) who had progressed on anti-HER2 antibody drug conjugates (ADC), at the San Antonio Breast Cancer Symposium in San Antonio, Texas (Press release, Merus, DEC 10, 2021, View Source [SID1234596771]).

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Andrew Joe, Chief Medical Officer at Merus, said, "We are pleased to present the final analysis of the triplet Zeno combination which has demonstrated clinically meaningful activity in heavily pretreated patients with HER2+/amplified MBC. We are encouraged by Zeno’s potential to be active in indications outside NRG1 fusion cancers, opening opportunities for potential collaborations in these areas."

The reported data are from the completed phase 2 study, designed to explore the efficacy of a triplet combination of Zeno plus trastuzumab and vinorelbine in MBC patients (NCT03321981). Preliminary results for patients treated with the triplet regimen were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Annual Meeting. The combination was observed to be well-tolerated in the run-in cohort and the cohort was expanded. The primary endpoint of the study was clinical benefit rate (CBR) at 24 weeks of 45%. Updated results from the cohort expansion are presented here:

At the efficacy data cut-off, March 31, 2021, 39 patients, with a median age of 57 and with a median number of five prior therapies, had received the Zeno-based triplet combination, 4 of whom were ongoing. All patients had completed at least 6 months of treatment or discontinued
37 patients with locally confirmed HER2 overexpression (IHC 3+ or IHC 2+/FISH-positive) were evaluable for antitumor activity
The clinical benefit rate (CBR: complete response + partial response + stable disease ≥24 weeks) per investigator assessment was 49% (18/37 patients; 90% CI 34 – 63)
Confirmed responses (per investigator) were reported in 10 patients, including 2 patients with complete response (CR)
Median duration of response was 4.2 months (90% CI 2.8 – 12.4), including 2 patients with CR lasting 4.2 and 7.2+ months, and 8 patients with partial responses (PR) lasting from 2.6 to 12.4 months
Median progression-free survival was 5.5 months (90% CI 4.1 – 5.6); 7 patients (19%) were censored. Estimated overall survival rates at 12 and 24 months were 73% and 61%, respectively
The combination was observed to be well tolerated, with AEs primarily related to chemotherapy
As previously reported, with completion of this phase 2 trial, Merus does not have plans to advance into a phase 3 clinical trial in metastatic breast cancer in the absence of a partner. The company continues to focus on the eNRGy trial to potentially support a BLA submission seeking a tumor agnostic indication for Zeno in patients with previously treated NRG1+ cancers.

The full poster is available on our website.

About Zeno
Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancers. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions.

On December 10, 2021 Candel Therapeutics, Inc. (Nasdaq: CADL), a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported a collaboration with Partnership for Accelerating Cancer Therapies (PACT) and the Cancer Immune Monitoring and Analysis Centers – Cancer Immunologic Data Commons (CIMAC-CIDC) to profile the biomarker response to a combination of CAN-2409 + valacyclovir in combination with anti-PD-1 and PD-L1 immune checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC) (Press release, Candel Therapeutics, DEC 10, 2021, View Source [SID1234596770]).

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Analysis of longitudinal biologic samples from a Candel phase 2 clinical trial will be performed by the CIMAC-CIDC research centers and sponsored by PACT. The assays proposed include in depth immunophenotyping of serial lung biopsies and peripheral blood samples obtained during the clinical trial. Candel’s clinical trial in NSCLC is designed to assess the tumor response to CAN-2409 when added to anti-PD-1 or PD-L1 immune checkpoint inhibitor (ICI) treatment after patients have inadequately responded to ICI with or without chemotherapy. The trial comprises three cohorts; 1) patients whose best response to ICI treatment has been stable disease; 2) patients who have initially responded to ICI treatment, but whose disease is now progressing; and 3) patients who have refractory disease, meaning they are progressing rapidly despite ICI treatment. In each of these settings, minimal to no response is expected from further ICI treatment. The collaboration will analyze samples from each of these cohorts with the aim to identify early biological indicators of response and further stratify potential responders to treatment.

"We have shown that local administration of CAN-2409 monotherapy induces significant remodeling of the tumor immune microenvironment coupled with systemic activation of the immune response," said Francesca Barone, MD, PhD, Vice President and Head of Research at Candel. "We are honored by the selection of our clinical trial by the PACT consortium, which provides an important validation of Candel’s approach to embed the highest levels of scientific rigor in our clinical trials. The data generated through this collaboration will broaden our understanding of the biological response to combination therapy of CAN-2409 with ICI, as we endeavor to bring effective new treatment options to patients with cancer."

About PACT

The Partnership for Accelerating Cancer Therapies (PACT) is a five-year public-private research collaboration launched by the National Institutes of Health, the Foundation for the National Institutes of Health (FNIH), and 12 leading pharmaceutical companies as part of the Cancer MoonshotSM Research Initiatives. The PACT initiative is partnered with the Cancer Immune Monitoring Analysis Centers (CIMACs) and the Cancer Immunologic Data Commons (CIDC) Network to develop and validate a set of standardized and harmonized biomarker assays that profile the response to immuno-oncology interventions, including combination therapies, oncolytic viral immunotherapy, and other novel immunotherapy treatments.

For more information about PACT, visit View Source

About CAN-2409

CAN-2409, Candel’s most advanced oncolytic viral immunotherapy candidate, is a replication-deficient adenovirus that delivers the herpes simplex virus thymidine kinase (HSV-tk) gene to cancer cells. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. The intra-tumoral administration results in the release of tumor-specific neoantigens in the microenvironment. At the same time, the adenoviral serotype 5 capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment. This creates the optimal conditions to induce a specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity.

Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. Furthermore, CAN-2409 presents a favorable tolerability profile; more than 700 patients have been dosed to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in non-small cell lung cancer, high-grade glioma, pancreatic cancer, and localized, non-metastatic prostate cancer in ongoing clinical trials.

For more information on this clinical study, please visit: View Source

On December 10, 2021 Novartis reported new Piqray (alpelisib) data indicating benefit across a broad range of patient and disease characteristics as seen in analyses from all three cohorts of BYLieve (Press release, Novartis, DEC 10, 2021, View Source [SID1234596768]). BYLieve is an ongoing Phase II, open-label, 3-cohort non-comparative study evaluating Piqray with endocrine therapy including men and pre- and postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (mBC) who have progressed on or after prior therapies, including CDK4/6 inhibitor plus endocrine therapy1-5. These data will be presented at the 2021 San Antonio Breast Cancer Symposium (SABCS) from December 7-10.

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"The data from all three cohorts of the BYLieve study have value for the medical community and for the patients we care for with mBC, because these cohorts show a benefit from alpelisib in the post-CDK4/6i setting for patients with HR+/HER2- PIK3CA-mutated cancer," said Dr. Hope S. Rugo, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center. "Beyond illustrating the efficacy and safety of alpelisib, regardless of the duration of prior CDK4/6i treatment, the data provide meaningful insights into how alpelisib may benefit different subgroups of patients."

Highlights from the BYLieve data presented at SABCS

BYLieve Cohort A (P1-18-03): Updated safety and efficacy data after 18 months of follow-up showed median overall survival improvement of 26.4 months (95% CI: 21.0-30.5) for patients treated with Piqray plus fulvestrant immediately following CDK4/6i plus an AI1. The most common all-grade adverse events (AEs) (n=127) were diarrhea (63.8%), hyperglycemia (59.8%), nausea (46.5%) and rash (31.5%)1.

BYLieve Cohort C (PD13-05): The third and final BYLieve cohort included patients who received chemotherapy or endocrine therapy as immediate prior treatment, who could have received prior CDK4/6i as well2.
The primary endpoint was met with 48.7% (95% CI: 39.3%-58.2%) of patients alive and without disease progression at six months2.
Data confirm clinically relevant activity of Piqray as a targeted therapy for PIK3CA as a driver oncogene2.
No new safety signals were observed, with the most common all-grade AEs (n=126) being hyperglycemia (65.1%), diarrhea (52.4%), nausea (40.5%) and rash (38.9%)2.
BYLieve Cohorts A & B (P1-18-08; P5-13-03; PD15-01): Exploratory biomarker and post-hoc analyses demonstrated efficacy with Piqray plus fulvestrant/letrozole in CDK4/6i-resistant mBC, as seen in patients with early discontinuation of the prior CDK4/6i (Cohort A: ≤6 months median PFS of 12.0 months and >6 months median PFS of 6.2 months; HR=0.51; 95% CI: 0.29-0.89; Cohort B: ≤6 months median PFS of 5.9 months and >6 months median PFS of 5.6 months; HR=0.72; 95% CI: 0.45-1.18), supporting the use of Piqray plus endocrine therapy as an immediate next-line option in these patients3. Grade ≥3 AEs were experienced by 84.6% (n=22) and 66.0% (n=66) of patients in the ≤6 months and >6 months subgroups, respectively, in Cohort A and by 62.5% (n=20) and 72.5% (n=66) of patients in the ≤6 months and >6 months subgroups, respectively, in Cohort B3.
Additionally, the exploratory ctDNA analysis from Cohorts A and B (median PFS of 7.3 months and 5.7 months in Cohorts A and Cohort B, respectively) found that Piqray was effective in the post-CDK4/6i setting regardless of endocrine therapy partner and tumor genomic profile and other mutations associated with CDK4/6i resistance4. Across the three cohorts no new safety signals were observed, even with longer exposure, as seen in Cohort A, confirming no cumulative toxicities with Piqray1-3.

An estimated 361,826 people are diagnosed with mBC worldwide each year, and approximately 40% of those with HR+/HER2- subtype have a PIK3CA mutation, which is associated with a poor prognosis8-9.

Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our SABCS Virtual Scientific Program data presentations (for registered participants).

About Piqray (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen7. Piqray is approved in 64 countries, including the US and European member states12.

Novartis is continuing to reimagine cancer with additional trials of Piqray. EPIK-B5 will be a large Phase III clinical trial of Piqray in combination with fulvestrant to complement the SOLAR-1 study13. Novartis is also studying the potential of Piqray in triple negative breast cancer (TNBC) in the EPIK-B3 Phase III clinical trial, in advanced HER2+ breast cancer in the EPIK-B2 Phase III clinical trial and in ovarian cancer in the EPIK-O Phase III clinical trial14-16.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with advanced breast cancer.

Important Safety Information from the PIQRAY EU SmPC
The most common ADRs and the most common grade 3 / 4 ADRs (reported at a frequency >20% and ≥2%, respectively) were plasma glucose increased, creatinine increased, gamma-glutamyltransferase increased, rash, lymphocyte count decreased, nausea, alanine aminotransferase increased, anaemia, fatigue, lipase increased, decreased appetite*, stomatitis, vomiting*, weight decreased, hypocalcaemia, plasma glucose decreased*, activated partial thromboplastin time prolonged*, alopecia**, diarrhoea, hypokalaemia, hypertension, nausea, creatinine increased, and mucosal inflammation (*<2% grade 3/4 ADRs reported, ** no grade 3/4 ADRs reported).

Piqray can cause serious side effects such as severe hypersensitivity, severe cutaneous reactions, hyperglycaemia, pneumonitis, diarrhoea and osteonecrosis of the jaw.

The following should be taken into consideration prior to or during treatment with Piqray:

Piqray should be permanently discontinued in patients with serious hypersensitivity reactions.

Piqray should not be initiated in patients with a history of severe cutaneous reactions, should be interrupted if signs or symptoms of severe cutaneous reactions are present, and permanently discontinued if a severe cutaneous reaction is confirmed.

Fasting glucose and HbA1c levels should be monitored frequently in the first 4 weeks of treatment, and patients should be advised of the signs and symptoms of hyperglycaemia.

In case of new or worsening respiratory symptoms, the patient should be evaluated for pneumonitis.

Patients should be advised to notify their physician if diarrhoea occurs.

Caution should be exercised when Piqray and bisphosphonates or denosumab are used together or sequentially. Piqray should not be initiated in patients with ongoing osteonecrosis of the jaw.

The efficacy and safety of Piqray has not been studied in patients with symptomatic visceral disease.

Animal studies suggest that Piqray may cause fetal harm in pregnant women. Therefore, as a precaution, women of childbearing potential should use effective contraception while receiving Piqray during treatment and at least 1 week after stopping treatment. Women should not breast feed for at least 1 week after the last dose of Piqray. Piqray may affect fertility in males and females.