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.

On June 4, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data on its investigational CD20xCD3 T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, and its first-in-class anti-CD79b antibody-drug conjugate, Polivy (polatuzumab vedotin), in non-Hodgkin lymphoma (NHL) will be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting from 4-8 June 2021 (Press release, Hoffmann-La Roche, JUN 4, 2021, View Source [SID1234583565]).

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!

"People with difficult-to-treat blood cancers such as non-Hodgkin lymphoma still need more options to help improve outcomes," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We are encouraged by promising data from our emerging T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, and the antibody-drug conjugate, Polivy, that demonstrate the potential of these novel immunotherapeutic approaches for various groups of patients."

While approximately 500,000 people worldwide are diagnosed with NHL each year, treatment options are currently limited and resistance to existing therapies or relapse following treatment is common.1 The most prevalent form of NHL, accounting for about 40% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma (DLBCL), that comes with a life expectancy of weeks or months if left untreated.2,3

In clinical trials to date, the investigational CD20xCD3 T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, have shown promising responses across multiple types of NHL, including relapsed or refractory (R/R) DLBCL and follicular lymphoma (FL). Pivotal data for these medicines are expected this year and Roche is targeting a regulatory filing for mosunetuzumab in FL by the end of 2021, following its U.S. Food and Drug Administration Breakthrough Therapy Designation granted in June 2020. Key data on mosunetuzumab and glofitamab to be presented at the meeting include:

Phase I NP30179 study investigating step-up dosing of glofitamab in heavily pre-treated R/R NHL, showed high, ongoing complete responses (CRs) and an acceptable safety profile. After a median follow-up of 6.3 months, results showed that glofitamab achieved a complete metabolic response rate, defined as the disappearance of metabolic tumour activity, of 71.4% in patients with aggressive (fast-growing) NHL. The most common adverse events (AEs) were cytokine release syndrome (CRS) (63.5%), neutropenia (38.5%), and pyrexia (32.7%); CRS events were mostly low grade and confined to the first cycle of treatment.4
Phase I/II GO40516 study of mosunetuzumab in combination with Polivy in R/R NHL showed promising efficacy and an acceptable safety profile. The regimen achieved a CR of 54.5% in all patients. Eighty six percent of patients evaluated had aggressive NHL, and these patients achieved a CR rate of 47.4%. The most frequent treatment-related AEs were neutropenia (45.4%), fatigue, nausea, and diarrhoea (all 36.4%) and CRS (9.1%; all Grade 1).5
Broad development programmes are ongoing for mosunetuzumab and glofitamab, including the phase III GO42909 trial investigating mosunetuzumab plus lenalidomide versus MabThera/Rituxan (rituximab) plus lenalidomide in R/R FL, which will soon be enrolling patients. For glofitamab, the phase III GO41944 open-label, randomised trial designed to evaluate the safety and efficacy of glofitamab plus gemcitabine and oxaliplatin (glofit-GemOx) versus MabThera/Rituxan plus GemOx in patients with R/R DLBCL, is also ongoing.

Roche is committed to pursuing treatment solutions that can be tailored to meet the various needs of both people living with NHL and healthcare professionals. Polivy is already a treatment option for people with R/R DLBCL and continues to show potential in multiple combinations. Key data at the meeting include:

New triplet combination of Polivy with MabThera/Rituxan and lenalidomide, which demonstrated promising activity in difficult-to-treat R/R DLBCL, based on results from the phase Ib/II GO29834 study. With a median follow-up of 9.7 months, median overall survival was 10.9 months (95% CI: 7.4–NE) and median progression-free survival was 6.3 months (95% CI: 4.5–9.7) in patients treated with the triplet. The most commonly reported Grade 3-4 AEs were neutropenia (58.0%), thrombocytopenia (14.0%), infections (14.0%) and anaemia (11.0%).6

As a leader in haematology development, Roche will continue to follow the science to expand and improve upon treatment options for healthcare providers and people with difficult-to-treat blood cancers.

Keep up to date with ASCO (Free ASCO Whitepaper) news and updates by using the hashtag #ASCO21 and follow Roche on Twitter via @Roche and on LinkedIn.

About Roche’s investigational bispecifics in haematology
Roche is currently developing two T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Mosunetuzumab and glofitamab differ in their structures, and both are being developed by Roche as part of our ongoing strategy to explore multiple bispecific formats, to identify those that maximise potential clinical benefits for patients. Mosunetuzumab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. Glofitamab is based on a novel structural format called ‘2:1’, which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions which bind to CD20, and one ‘Fab’ region which binds to CD3. The clinical development programmes for mosunetuzumab and glofitamab include ongoing investigations of these molecules as monotherapies and in combination with other medicines, for the treatment of people with CD20-positive B-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

About Polivy (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of NHL, making it a promising target for the development of new therapies.7,8 Polivy binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.9,10 Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL. Polivy is marketed in the US by Genentech as Polivy (polatuzumab vedotin-piiq), with piiq as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/Ib, multicentre, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of glofitamab. In this study, glofitamab is assessed as a single-agent and in combination with Gazyva/Gazyvaro (obinutuzumab), following pre-treatment with a one-time, fixed-dose of Gazyva/Gazyvaro, in people with relapsed or refractory (R/R) B-cell NHL. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose and tolerability.

About the GO40516 study
The GO40516 study [NCT03671018] is a phase I/II, multicentre, open-label study, evaluating the efficacy, safety, tolerability and pharmacokinetics of mosunetuzumab in combination with Polivy in people with B-cell NHL. It consists of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with R/R DLBCL and 2L+ R/R FL. Outcome measures include best overall response rate, maximum tolerated dose and tolerability.

About the GO29834 study
The GO29834 study [NCT02600897] is a phase Ib/II, multicentre, open-label study, evaluating the efficacy and safety of Polivy with MabThera /Rituxan (rituximab) and lenalidomide in R/R DLBCL. Outcome measures include complete response and tolerability.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan, Gazyva/Gazyvaro, Polivy, Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, and cevostamab, targeting FcRH5 and CD3; Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On June 4, 2021 Novartis reported that results from the pivotal Phase III RATIONALE 302 trial showing the investigational anti-PD-1 immune checkpoint inhibitor tislelizumab improved overall survival (OS) versus chemotherapy (median 8.6 months vs. 6.3 months, p=0.0001) (Press release, Novartis, JUN 4, 2021, View Source [SID1234583564]).1 The study evaluated tislelizumab in patients with unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who had received prior systemic therapy. Results were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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!

Results from RATIONALE 302 in ESCC showed tislelizumab extended median OS by 2.3 months compared to chemotherapy with a 30% reduction in the risk of death (HR=0.70, 95% CI: 0.57-0.85, p=0.0001).1 In PD-L1 positive patients, tislelizumab extended median OS by 3.5 months with a 46% reduction in the risk of death (HR=0.54, 95% CI: 0.36-0.79, p=0.0006).1

"These data show that tislelizumab has the potential to help patients with esophageal squamous cell carcinoma – one of the deadliest types of cancers – live longer," said Jeff Legos, Ph.D., MBA, Senior Vice President and Head of Oncology Drug Development. "We are excited about these results from the newest asset in our portfolio of transformational medicines and look forward to sharing these data with regulatory authorities, as we continue to explore the full potential of this uniquely designed anti-PD-1 antibody."

Treatment with tislelizumab demonstrated median progression-free survival (PFS) of 1.6 months compared to 2.1 months (HR=0.83, 95% CI: 0.67–1.01). Tislelizumab demonstrated a higher and more durable anti-tumor activity than chemotherapy (objective response rate [ORR], 20.3% vs. 9.8%; median duration of response [DoR], 7.1 months vs. 4.0 months).1

The discontinuation rate due to treatment-related adverse events (TRAEs) was lower in patients who received tislelizumab (6.7%) compared to chemotherapy (13.8%). The most common all-grade TRAEs (≥10%) with tislelizumab were increased aspartate aminotransferase (11.4%), anemia (11%) and hypothyroidism (10.2%). No new safety signals were identified.1

"Most patients with this type of esophageal cancer are diagnosed with advanced disease, resulting in a poor prognosis for this difficult-to-treat cancer," said Jaffer Ajani, M.D., professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. "The impact tislelizumab had on survival compared to chemotherapy in this study is highly meaningful and encouraging news for patients, caregivers and treating oncologists."

Esophageal squamous cell carcinoma is the most common type of esophageal cancer globally and the sixth leading cause of cancer-related death worldwide.3 Each year, esophageal cancer claims nearly as many lives as colon cancer across the globe.3 More than two-thirds of patients with ESCC have advanced or metastatic disease at the time of diagnosis.4 The average five-year survival rate is only five percent.5

RATIONALE 302 is a randomized, global Phase III study assessing tislelizumab versus chemotherapy in patients with advanced unresectable/metastatic ESCC after prior systemic therapy. The primary endpoint is OS in the intent-to-treat (ITT) population. The key secondary endpoint is OS in PD-L1 positive patients (vCPS ≥10%). Additional secondary endpoints included PFS, ORR, DoR and safety endpoints.1

Data on tislelizumab in MSI-H cancers presented
The RATIONALE 209 study reported that tislelizumab showed durable anti-tumor activity in patients with previously treated, locally advanced, unresectable or metastatic microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) cancers, which are known to be more responsive to immune checkpoint modulation. Treatment with tislelizumab demonstrated an ORR of 45.9% among all tumor types, including four complete responses (CR) and 30 partial responses (PR). No disease progression was reported in the 34 responders (CR + PR), with a 12-month DoR rate of 100%).2

Five percent of patients treated with tislelizumab discontinued treatment due to TRAEs, and no new safety signals were identified. Grade ≥3 TRAEs occurred in 42.5% of patients.2

MSI-H cancer cells have a defect in the ability to correct mistakes that occur when DNA is copied, leading to mutations that contribute to cancerous growth. Many types of cancer may have a high level of microsatellite instability, but it is seen most often in CRC, gastric cancer and endometrial cancer.6

RATIONALE 209 is a single-arm, open-label Phase II study evaluating the efficacy and safety of tislelizumab monotherapy in adult patients with previously treated, locally advanced, unresectable or metastatic histologically confirmed MSI-H/dMMR solid tumors. Radiological imaging was performed at nine weeks, then every six weeks for the first year of therapy and every 12 weeks thereafter. The primary endpoint was IRC-assessed ORR. Secondary endpoints included time to response, DoR, disease control rate, PFS, OS and safety.2

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 tislelizumab
Tislelizumab was specifically engineered to minimize binding to macrophage Fcγ receptors, a potential mechanism of anti–PD-1 resistance.7 Tislelizumab is an important component of Novartis’s immuno-oncology strategy – one of four bold approaches to reimagining cancer and transforming patients’ lives.

In an agreement finalized earlier this year, BeiGene granted Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan through a collaboration and license agreement.

On June 4, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported it will host an investor and analyst video webcast event on Thursday, June 10, 2021 at 12:00 PM ET following the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, MEI Pharma, JUN 4, 2021, View Source [SID1234583563]). The event will include a review of the zandelisib program, including recent data presented at ASCO (Free ASCO Whitepaper), and commentary from key opinion leader Deepa Jagadeesh, M.D., MPH, a board-certified medical oncologist/hematologist and assistant professor, Cleveland Clinic Lerner College of Medicine, Lymphoma and Bone Marrow Transplant Program, and Taussig Cancer Institute. The event will include additional zandelisib data as well as an overview and update of MEI’s business.

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!

Video Webcast Information
You can access the live video webcast under the investor relations section of MEI’s website on the "Events and Presentation" page at: www.meipharma.com. A replay of the video webcast will be archived for at least 30 days after the conclusion of the live event.