On June 4, 2021 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that Dr. Mark Souweidane, Memorial Sloan Kettering Cancer Center ("MSK") and Weill Cornell Medicine will present interim phase 1 dose-escalation data for omburtamab for diffuse intrinsic pontine glioma ("DIPG") at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Virtual Annual Meeting on June 4, 2021 (Press release, Y-mAbs Therapeutics, JUN 4, 2021, View Source [SID1234583571])

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The phase 1 dose-escalation study with administration via convection enhanced delivery ("CED"), showed that dosing of omburtamab radiolabeled with 8 mCi of 124-Iodine appeared to be well-tolerated and provided distribution volume to potentially cover tumor volumes of up to 20 cm3. The median overall survival of all 46 patients in the study increased by three to four months as compared to the historical control group. The study will continue dose escalation for both infused volume and dose.

"We are excited to share these results that significantly broaden the potential reach of omburtamab, which would be addressing a clear unmet medical need. The results pave the way for our multicenter phase 2 study in DIPG later this year, where we expect to give up to three repeated doses of omburtamab," stated Thomas Gad, founder, Chairman and President.

Dr. Claus Moller, Chief Executive Officer, continued, "We are expanding our omburtamab franchise significantly this year. While the iodine labeled omburtamab targets DIPG, CNS/LM from neuroblastoma and DSRCT, we have also initiated clinical trials for medulloblastoma and B7-H3 positive CNS metastasis with our lutetium labeled omburtamab."

Researchers at MSK developed omburtamab, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the product.

On June 4, 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) (Press release, Gilead Sciences, JUN 4, 2021, View Source [SID1234583570]). In this subgroup analysis of brain metastases-negative patients who received only one line of prior systemic therapy in the metastatic setting in addition to having disease recurrence or progression within 12 months of (neo)adjuvant chemotherapy, Trodelvy improved progression-free survival (PFS), with a 59% reduction in the risk of disease worsening or death (HR: 0.41; 95% CI: 0.22-0.76) and a median PFS of 5.7 months (n=33) versus 1.5 months with chemotherapy (n=32). Trodelvy also extended median overall survival to 10.9 months versus 4.9 months with chemotherapy (HR: 0.51; 95% CI: 0.28-0.91). The results were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #1080).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In patients with relapsed or refractory metastatic triple-negative breast cancer, outcomes are typically poor – especially among patients who progress within 12 months of (neo)adjuvant chemotherapy," 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. "In the Phase 3 ASCENT study, Trodelvy was the first treatment to demonstrate a proven survival advantage in pre-treated patients with locally advanced or metastatic TNBC, and the analysis presented at ASCO (Free ASCO Whitepaper) reaffirms this benefit over standard of care with important new data in the second-line setting."

Additional results showed Trodelvy demonstrated a higher overall response rate compared with chemotherapy (30% versus 3%). Efficacy results from this subgroup were consistent with those observed in the overall ASCENT study population.

The safety profile of Trodelvy in this subgroup was consistent with prior reports. The most frequent Grade ≥3 treatment-related adverse reactions for Trodelvy compared to chemotherapy were neutropenia (61% versus 21%), leukopenia (9% versus 0%), diarrhea (6% versus 0%), anemia (3% versus 6%), and fatigue (3% versus 0%). One patient in this subgroup who received Trodelvy experienced febrile neutropenia. Adverse reactions leading to treatment discontinuation were low across both groups (6% in each). 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.

"With Trodelvy, we continue to challenge the standard of care in locally advanced and metastatic TNBC. The efficacy observed in the second-line metastatic setting with Trodelvy is highly meaningful, since many patients will progress quickly following chemotherapy. Among these patients, we see median overall survival more than doubled where need is particularly great," said Daejin Abidoye, MD, Senior Vice President, Head of Oncology Clinical Development, Gilead Sciences. "We are committed to improving the prognosis for people with this aggressive cancer, and as we continue to study Trodelvy, we are encouraged by this proven efficacy in TNBC."

Two additional ASCENT subgroup analyses that support the efficacy benefit of Trodelvy were also presented at the meeting – one evaluating Trodelvy efficacy by patients’ age (Abstract #1011) and the other comparing Trodelvy with specific single-agent chemotherapy chosen by the patients’ treating physicians (Abstract #1077).

About Triple-Negative Breast Cancer (TNBC)

TNBC is an aggressive type of breast cancer, accounting for approximately 15% of all breast cancers. The disease is diagnosed more frequently in younger and premenopausal women and is more prevalent in African American and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2. Medicines targeting these receptors therefore are not typically effective in treating TNBC.

About the ASCENT Study

The Phase 3 ASCENT study, an open-label, active-controlled, randomized confirmatory trial, enrolled more than 500 patients with relapsed/refractory metastatic triple-negative breast cancer who had received two or more prior systemic therapies, including a taxane, at least one of them for metastatic disease. Patients were randomized to receive either Trodelvy or a chemotherapy chosen by the patients’ treating physicians. The primary efficacy outcome was PFS in patients without brain metastases at baseline, as measured by a blinded, independent, centralized review using RECIST v1.1 criteria. Additional efficacy measures included PFS for the full population, including all patients with and without brain metastases, and overall survival. More information about ASCENT is available at View Source

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein frequently expressed in multiple types of epithelial tumors, including metastatic triple-negative breast cancer and metastatic urothelial cancer, where high expression is associated with poor survival and relapse.

In the U.S., Trodelvy is indicated for the treatment of:

Adult patients with unresectable locally advanced or metastatic triple-negative breast cancer who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.
Beyond the regulatory approvals of Trodelvy in the U.S., regulatory reviews for Trodelvy in metastatic triple-negative breast cancer are currently underway in the EU, U.K., Canada, Switzerland and Australia, as well as in Singapore through our partner Everest Medicines. Trodelvy is also being investigated as potential 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.

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 June 4, 2021 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of highly differentiated immuno-oncology therapeutics for patients, reported new clinical data from its ongoing Phase 1/2a clinical trial of inupadenant (EOS-850), a next-generation adenosine receptor (A2AR) antagonist, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2021 (Press release, iTeos Therapeutics, JUN 4, 2021, View Source [SID1234583569]). Updated results from the single-agent dose-escalation and expansion portions of the trial provided evidence of durable antitumor activity in patients with advanced solid tumors and indicated safety consistent with previously reported results. Three serious adverse events considered possibly related to treatment with inupadenant had plausible alternate causes and do not represent a new safety concern for the program. Additionally, preliminary analyses of pre-treatment tumor biopsies indicated that the expression of A2AR is associated with clinical outcomes in patients with solid tumors treated with single agent inupadenant.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased with the durability of the anti-tumor responses we have observed to date with our highly selective A2AR antagonist, inupadenant, in patients with advanced cancers. These early-stage results support the development for the treatment of cancer of inupadenant, a selective inhibitor of A2AR, which is known to play a crucial role in immunosuppression in the tumor microenvironment." said Joanne Jenkins Lager, M.D., chief medical officer of iTeos Therapeutics. "We have used a proprietary assay to identify A2AR expression as a biomarker that may be predictive of clinical benefit. These new biomarker findings provide insight into the mechanism of action of inupadenant, informing our selection of potential indications, and may allow us to identify patients more likely to benefit from inupadenant. We are continuing to evaluate combinations with pembrolizumab and chemotherapy in our ongoing Phase 1b/2a trial with the goal of improving outcomes for patients."

Phase 1/2a monotherapy Study Design and Results
The ongoing Phase 1/2a trial is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of inupadenant monotherapy to define the maximum tolerated dose (MTD) and recommended Phase 2 dose of inupadenant as a single agent and in combination with pembrolizumab and/or chemotherapy in patients with advanced solid tumors. As of the data cut-off (February 26, 2021), 43 patients had enrolled in the single-agent dose-escalation and expansion parts of the study.

Results presented at ASCO (Free ASCO Whitepaper) 2021 provided an update on 21 patients enrolled in the single-agent dose-escalation and new data on 22 patients enrolled in the dose expansion.

Durable responses and stable disease greater than six months were observed in five patients with advanced solid tumors, including:

previously reported partial responses: ongoing for more than 12 months in one patient with castrate-resistant prostate cancer, and lasting for more than 8 months in one patient with melanoma resistant to both pembrolizumab and ipilimumab; and
stable disease in a patient with non-small cell lung cancer enrolled in the expansion, with ongoing treatment for more than 10 months.
The safety of inupadenant monotherapy was consistent with previously presented data. The most frequent adverse events were fatigue, anemia, decreased appetite and constipation. Drug-related serious adverse events (acute myocardial infarction, atrial fibrillation, and pericardial effusion) were reported in three of the 43 enrolled patients.

Evaluation of pre-treatment biopsies indicated that higher expression of A2AR was associated with longer survival and either tumor regression or stable tumor size in patients with solid tumors treated with single agent inupadenant.

The e-poster and abstract can be accessed on the ASCO (Free ASCO Whitepaper) conference website. The abstract and presentation details are as follows:

Title: Phase 1 trial of the adenosine A2A receptor antagonist inupadenant (EOS-850): Update on tolerability, and antitumor activity potentially associated with the expression of the A2A receptor within the tumor.
Session Title: Developmental Therapeutics—Immunotherapy
Abstract #: 2562
Authors: Laurence Buisseret, et al.

Further Clinical Development of Inupadenant
Based on the promising Phase 1/2a data to date, iTeos plans to further evaluate inupadenant in combination with pembrolizumab and in combination with chemotherapy in Phase 1b/2 studies, with an initial focus on patients with castrate-resistant prostate cancer, anti-PD-1-resistant melanoma and triple negative breast cancer. iTeos will continue to evaluate A2AR and other potential predictive biomarkers in the inupadenant clinical development program to ensure optimal therapeutic combinations and identify patients most likely to benefit from treatment.

About Inupadenant
Elevated levels of adenosine found in the tumor microenvironment are known to be immunosuppressive, by inhibiting A2AR, the only high-affinity adenosine receptor expressed on different immune cells found in the tumor micro-environment. Inupadenant (EOS-850) is the first insurmountable A2AR antagonist tailored for application in immuno-oncology, currently in clinical development. Inupadenant was designed by iTeos’ scientists to remain potent at the high adenosine concentrations found in the tumor micro-environment and maintain continuous target coverage in multiple tumor types. Inupadenant has a very high selectivity for A2AR compared to the other adenosine receptors and is non brain penetrant, two characteristics that should improve its safety. With this profile, we believe that inupadenant has the potential for enhanced antitumor activity as compared to other A2AR antagonists currently in clinical development.

On June 4, 2021 Novartis reported the first published mature overall survival (OS) and updated overall response rate (ORR) data following treatment with Tabrecta (capmatinib) in adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to MET exon 14 skipping (METex14)1-3 (Press release, Novartis, JUN 4, 2021, View Source [SID1234583567]). Data from the ongoing, pivotal, multi-cohort Phase II GEOMETRY mono-1 study will be presented today during the 2021 Annual American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Meeting (Poster Discussion Session, Lung Cancer—Non-Small Cell Metastatic; June 4, 2021, 9:00 AM-10:00 AM CT; abstract 9020).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This new analysis further supports Tabrecta as a cornerstone targeted treatment for METex14 NSCLC patients and highlights the importance of biomarker testing," said Juergen Wolf, MD, from the Center for Integrated Oncology, University Hospital Cologne, and lead investigator of the GEOMETRY study. "The impressive overall survival outcome and confirmed outstanding response in the first-line setting will help oncologists decide upon a therapeutic option for patients."

The analysis includes new data from the treatment-naïve (1L) expansion cohort 7 and previously-treated (2L+) cohort 6, and mature data from previously-reported cohorts, for a total of 160 patients1,2.

"The introduction of Tabrecta a year ago dramatically changed the treatment landscape for patients with METex14 NSCLC. Now we have further evidence that Tabrecta, the market-leading treatment specifically for METex14 NSCLC patients4, has the potential to help people live longer," said Jeff Legos, Senior Vice President, Head of Oncology Drug Development, Novartis Oncology.

The results presented today provide additional data on the efficacy of Tabrecta in both treatment-naïve and previously-treated patients with METex14 metastatic NSCLC 2:

Overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1:
67.9% (95% CI: 47.6, 84.1) and 65.6% (95% CI: 46.8, 81.4) among treatment-naïve patients (Cohort 5b; n= 28 and Cohort 7; n= 32 patients, respectively)
40.6% (95% CI: 28.9, 53.1) and 51.6% (95% CI: 33.1, 69.8) among previously-treated patients (Cohort 4; n= 69 and Cohort 6; n= 31 patients, respectively)
Median duration of response (DOR) based on BIRC assessment:
12.6 months (95% Cl: 5.6‑NE) and NE (95% CI: 5.5-NE) among treatment-naïve patients (Cohort 5b; n= 28 and Cohort 7; n= 32 patients, respectively)
9.7 months (95% Cl: 5.6‑13.0) and 8.4 months (95% Cl: 4.2‑NE) among previously-treated patients (Cohort 4; n= 69 and Cohort 6; n= 31 patients, respectively)
Overall survival (OS):
20.8 months (95% CI: 12.42, NE [not estimated]) among treatment-naïve patients (Cohort 5b; n= 28)
13.6 months (95% CI: 8.61, 22.24) among previously-treated patients (Cohort 4; n= 69)
Median OS for expansion Cohorts 6 & 7 are not reached
No new safety signals or unexpected safety findings were observed. Ninety-eight percent of subjects had at least one adverse event (AE) of any grade and 50.9% of subjects had at least one serious adverse event (SAE). Thirteen percent were suspected to be treatment-related. The most common adverse events (>20%, all grades) across all cohorts were peripheral edema, nausea, vomiting, increased blood creatinine, dyspnea, fatigue and decreased appetite. The majority of AEs were grade 3 or 42.

Currently, the five-year survival rate for lung cancer is less than 20%5, decreasing further when the disease is diagnosed at later stages6. Nearly one in three patients with metastatic NSCLC may have an actionable mutation7,8. METex14 has been reported to occur in 3%-4% of metastatic NSCLC cases9. Many patients with mutations that lead to METex14 are not diagnosed with NSCLC until their disease has progressed to later stages and often have poor prognosis10,11.

A separate analysis of patient-reported outcomes (PROs) evaluated cough, delayed time to lung symptom deterioration, and quality of life (QoL) in NSCLC patients with METex14 (abstract 9056)3.

Median time to definitive deterioration (TTDD) in global health status (GHS) was 16.6 months (95% CI: 9.7, NE) and 12.4 months (95% CI: 4.2, 19.4) in 1L and 2L+ patients, respectively
Median TTDD for cough and chest pain was NE in both 1L and 2L+ patients, and for dyspnea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE), respectively
An exploratory post hoc analysis evaluated QLQ-LC13 symptoms (cough, chest pain, and dyspnea) over time for patients achieving a clinical response, as assessed by BIRC, found these symptoms improved at all cycles in patients achieving clinical complete response (CR) or partial response, while symptom worsening was seen in those with no clinical response
Additionally, a retrospective analysis of GEOMETRY mono-1 validates the clinical utility of liquid biopsy testing to identify METex14 positive patients for treatment with Tabrecta (Poster Session: Lung Cancer—Non-Small Cell Metastatic; abstract 9111)12.

Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO (Free ASCO Whitepaper)21 Virtual Scientific Program data presentations (for registered participants).

About GEOMETRY mono-1
GEOMETRY mono-1 is a Phase II a multi-center, non-randomized, open-label, multi-cohort study in adult patients with EGFR wild-type, ALK-negative rearrangement, metastatic NSCLC harboring mutations that lead to MET exon-14 skipping who received capmatinib tablets 400 mg orally twice daily.

Patients were assigned to cohorts on the basis of MET status and previous lines of therapy13. The primary endpoint was overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) evaluated by BIRC.

About Tabrecta (capmatinib)
Tabrecta (capmatinib) is a kinase inhibitor that targets MET. Tabrecta was discovered by Incyte and licensed to Novartis in 2009. Under the Agreement, Incyte granted Novartis worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications. In May 2020, Tabrecta was approved by the US Food and Drug Administration (FDA) for adult patients with metastatic NSCLC whose tumors have a mutation that leads to METex14 as detected by an FDA-approved test. This indication was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

In June 2020, Tabrecta was approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for adult patients with metastatic NSCLC whose tumors have a mutation that leads to METex14 as detected by an FDA-approved test. Tabrecta was also approved in Hong Kong in February 2021 and Switzerland in April 2021.

Novartis and Lung Cancer
Lung cancer is the most common cancer worldwide, accounting for more than 2 million new cases diagnosed each year14. There are two main types of lung cancer – small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)15,16. NSCLC accounts for approximately 85% of lung cancer diagnoses, resulting in nearly 2 million new cases each year14,16. More people die of lung cancer every year than any other cancer type14. Treatment options are limited for people with lung cancer who experience cancer growth or progression while on current standard of care treatments17-19.

Novartis is committed to developing best-in-class treatments for lung cancer patients around the world. With a focus on both targeted, personalized medicine and the role of newer core immuno-oncology therapies, the lung cancer drug development program at Novartis is among the most robust in the industry. Novartis research activities are informed by our long-term relationships with leading lung cancer thought leaders and patient advocates. With them, Novartis is committed to reimagining the treatment of lung cancer.

Indication
TABRECTA (capmatinib) tablets is a prescription medicine used to treat adults with a kind of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body or cannot be removed by surgery (metastatic), and whose tumors have an abnormal mesenchymal-epithelial transition (MET) gene.

The effectiveness of TABRECTA in these patients is based on a study that measured 2 types of response to treatment (response rate and duration of response). There is no clinical information available to show if patients treated with TABRECTA live longer or if their symptoms improve. There are ongoing studies to find out how TABRECTA works over a longer period of time.

It is not known if TABRECTA is safe and effective in children.

Important Safety Information
TABRECTA may cause serious side effects, such as lung or breathing problems. TABRECTA may cause inflammation of the lungs during treatment that may lead to death. Patients should be advised to contact their health care provider right away if they develop any new or worsening symptoms, including cough, fever, trouble breathing, or shortness of breath.

TABRECTA may cause abnormal blood test results, which may be a sign of liver problems. Patients should be advised that their health care provider will do blood tests to check their liver before starting and during treatment with TABRECTA. Patients should be advised to contact their health care provider right away if they develop any signs and symptoms of liver problems including the skin or the white part of their eyes turning yellow (jaundice), dark or "tea-colored" urine, light-colored stools (bowel movements), confusion, loss of appetite for several days or longer, nausea and vomiting, pain, aching, or tenderness on the right side of the stomach area (abdomen), or weakness or swelling in the stomach area.

The skin may be sensitive to the sun (photosensitivity) during treatment with TABRECTA. Patients should be advised to use sunscreen or wear clothes that cover their skin during treatment with TABRECTA to limit direct sunlight exposure.

For women of reproductive potential, TABRECTA can harm their unborn baby. They should use an effective method of birth control during treatment with TABRECTA and for 1 week after the last dose. Men who have partners who can become pregnant should use effective birth control during treatment with TABRECTA and for 1 week after the last dose.

Before taking TABRECTA, patients should tell their health care provider about all their medical conditions, including if they have or have had lung or breathing problems other than lung cancer, have or have had liver problems, or if they are pregnant or plan to become pregnant, as TABRECTA can harm their unborn babies. Females who are able to become pregnant should have a pregnancy test before they start treatment with TABRECTA and should use effective birth control during treatment and for 1 week after the last dose of TABRECTA. Patients should be advised to talk to their health care provider about birth control choices that might be right for them during this time and to tell their health care provider right away if they become pregnant or think they may be pregnant during treatment with TABRECTA. Males who have female partners who can become pregnant should use effective birth control during treatment and for 1 week after their last dose of TABRECTA.

Patients should tell their health care provider about all the medicines they take or start taking, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of TABRECTA include swollen hands, ankles, or feet (peripheral edema); nausea and/or vomiting; tiredness and/or weakness (fatigue, asthenia); shortness of breath (dyspnea); loss of appetite; changes in bowel movements (diarrhea or constipation); cough; pain in the chest; fever (pyrexia); back pain; and decreased weight.

On June 4, 2021 Purple Biotech Ltd. ("Purple Biotech", or the "Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies by overcoming tumor immune evasion and drug resistance, reported the presentation of new data from the first dose level cohort of its ongoing Phase 1/2 clinical trial of NT219, at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, being held virtually June 4-8, 2021 (Press release, Purple Biotech, JUN 4, 2021, View Source [SID1234583566]). The Phase 1/2 study is evaluating NT219 as monotherapy for the treatment of solid tumors, in addition to a subsequent dose escalation of NT219 in combination with cetuximab, an epithelial growth factor receptor (EGFR) blocking monoclonal antibody, for the treatment of recurrent and/or metastatic solid tumors and squamous cell carcinoma of the head and neck cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As of the cutoff date (April 25th, 2021), six patients have been enrolled into the study, including three subjects with advanced solid tumors in the first cohort receiving 3 mg/kg of NT219 as a single agent, and three subjects in the second cohort receiving 6mg/kg of NT219 as monotherapy.

Initial results from the first dose level cohort revealed NT219 was well-tolerated with minimal adverse events. In addition, a partial response was observed in a patient with refractory gastroesophageal junction cancer, previously treated with four prior lines of therapies. For this patient, who has been treated for 22 weeks, a complete remission was seen at the largest target lesion and at one non-target lesion, while stable disease was observed at the other non-target lesion.

"We are encouraged by these initial safety and efficacy results from this first-in-human study of NT219," said Alberto Bessudo, M.D., a medical oncologist and hematologist at California Cancer Associates for Research & Excellence, who presented the data at ASCO (Free ASCO Whitepaper). "This study is especially compelling because NT219 uniquely targets the IRS protein to degradation by utilizing a covalent, irreversible inhibition strategy. Based on the preclinical results observed to date, by targeting the IRS1/2 and STAT3 pathways NT219 has the potential to significantly shrink tumors, prevent and reverse tumor resistance when administered as a monotherapy, as well as in combination with existing oncology therapies."

"Our innovative approach to overcoming tumor immune evasion and drug resistance is focused on interactions within the microenvironment of the tumor, not just targeting the tumor as an isolated feature," said Bertrand C. Liang, M.D., Ph.D., Chief Medical Officer of Purple Biotech. "It has been demonstrated clinically that IRS and STAT3 proteins are central in defining tumor responsiveness to therapy. Indeed, STAT3 has been seen to play a role in treatment response, and IRS is a novel target with recent promising findings and interest in oncology. While still early in the trial, we are very excited by these initial clinical results and expect to report additional data from higher dose levels of this study in the second half of this year."

NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3, known important oncogenic drivers and major drug resistance pathways in hard-to-treat cancers. The primary objectives of the open-label Phase 1/2 trial are to evaluate safety, assess pharmacokinetics, identify the recommended dose to be studied in the Phase 2 portion, and establish preliminary efficacy of NT219. The Phase 1 portion of the study will encompass a dose escalation evaluation of NT219 monotherapy administered weekly in patients with refractory advanced solid tumors. Upon reaching the third dose level of NT219, a second cohort of patients, with recurrent or metastatic squamous cell carcinoma of the head and neck or colorectal adenocarcinoma, will be administered weekly with NT219, and dose escalated, in combination with cetuximab.