On May 26, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the company will be participating in the following investor conferences (Press release, Guardant Health, MAY 26, 2022, View Source [SID1234615120]).

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William Blair 42nd Annual Growth Stock Conference in Chicago, IL
Presentation on Tuesday, June 7th at 11:20 a.m. Central Time
Goldman Sachs 43rd Annual Global Healthcare Conference in Rancho Palos Verdes, CA
Fireside Chat on Tuesday, June 14 th at 9:20 a.m. Pacific Time
Interested parties may access live and archived webcasts of the sessions on the "Investors" section of the company website at: www.guardanthealth.com.

On May 26, 2022 Ipsen (Euronext: IPN; ADR: IPSEY) reported encouraging data to be presented for the multi-targeted tyrosine kinase inhibitor (TKI), Cabometyx (cabozantinib), across a range of cancer types at this year’s American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO 2022) to be held on 3-7 June (Press release, Ipsen, MAY 26, 2022, View Source [SID1234615119]). Data presentations will include findings in metastatic non-small cell lung cancer (NSCLC), as well as established indications of advanced renal cell carcinoma and radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC). These data show that the therapeutic potential of Cabometyx as a key treatment option in a broad range of tumors is continuing to be realized.

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Updated outcomes from the multicenter Phase Ib COSMIC-021 trial evaluating the combination of Cabometyx plus atezolizumab in an expanded patient population in metastatic NSCLC demonstrate encouraging clinical activity with manageable toxicity in people previously treated with an immune checkpoint inhibitor (ICI).1 These data lay the foundations for the potential of Cabometyx in metastatic NSCLC which is being further examined in the ongoing Phase III CONTACT-01 trial. This trial is evaluating the combination of Cabometyx plus atezolizumab vs docetaxel in patients with metastatic NSCLC previously treated with an ICI and platinum-containing chemotherapy, and topline results of the study are expected to be announced in the second half of 2022.

"Currently, first-line immunotherapy with or without chemotherapy is the standard of care for patients with metastatic NSCLC but there is a real need for additional effective treatment options for those patients who progress after a prior immunotherapy," said Santiago Ponce-Aix, M.D., Head of Drug Development Department, Institute Gustave Roussy, France, and an investigator in the COSMIC-021 trial. "These new data are encouraging as they show the potential role of Cabometyx in creating an environment which may enhance atezolizumab’s activity in NSCLC. We look forward to further data evaluating this combination for this patient population where there remains such a high unmet medical need."

"The therapeutic potential of Cabometyx as a treatment option against a broad range of tumors including NSCLC is continuing to be evaluated and these data demonstrate our ambition to bring meaningful new treatments to patients. These latest data support the potential role of Cabometyx to positively impact treatment when paired with immunotherapy, and we will continue to evaluate Cabometyx as both a monotherapy and in combination with other innovative therapies for the most difficult-to-treat cancers," said Dr. Howard Mayer, Executive Vice President and Head of Research and Development at Ipsen.

An exploratory analysis will also be presented investigating the relationship between depth of response (DepOR) and clinical outcomes in CheckMate -9ER, evaluating Cabometyx in combination with nivolumab vs sunitinib in previously untreated advanced renal cell carcinoma.2 DepOR was defined as the best percent reduction from baseline in sum of diameters of target lesions. Overall, greater proportions of patients receiving Cabometyx plus nivolumab demonstrated deeper responses vs sunitinib. Regardless of treatment, deeper responses were generally associated with improved progression-free survival (PFS) and overall survival.2

Additionally, two new data analyses from the pivotal Phase III trial COSMIC-311 evaluating Cabometyx in RAI-R DTC will be presented. One analysis relates to outcomes for prespecified subgroups based on the baseline histology subtypes of papillary and follicular thyroid cancers, with results showing Cabometyx maintained superior efficacy vs placebo irrespective of histology subtype.3 Median PFS was 9.2 months for Cabometyx vs 1.9 months for placebo in the papillary thyroid cancer (PTC) subgroup (HR 0.27 95% CI, 0.17-0.43) and 11.2 months vs 2.5 months in the follicular thyroid cancer (FTC) subgroup (HR 0.18 95% CI, 0.10-0.31). The overall response rate (ORR) was 15% for Cabometyx vs 0% for placebo in the PTC subgroup and 8% vs 0% in the FTC subgroup.3

Another analysis will be presented related to outcomes for prespecified subgroups who received prior lenvatinib and/or sorafenib treatment. The data from this analysis showed Cabometyx maintained its PFS vs placebo irrespective of prior lenvatinib and/or sorafenib treatment.4 Median PFS across the different groups included 16.6 months for Cabometyx vs 3.2 months for placebo in prior sorafenib (no lenvatinib) (HR 0.13, 95% CI 0.06–0.26), 5.8 months vs 1.9 months in prior lenvatinib (no sorafenib) (HR 0.28, 95% CI 0.16-0.48), and 7.6 months vs 1.9 months in prior sorafenib and lenvatinib (HR 0.27, 95% CI 0.13–0.54).4

The safety profile identified in COSMIC-021, CheckMate -9ER and COSMIC-311 was consistent with that previously observed for Cabometyx in monotherapy and in combination.

Ipsen thanks the patients and investigators involved in the COSMIC-021, CheckMate -9ER and COSMIC-311 clinical trials.

ENDS

More information can be found during the presentation sessions outlined below:

Lead author

Indication

Abstract title

Presentation number/timing (CDT)

Neal

NSCLC

Cabozantinib (C) Plus Atezolizumab (A) or C Alone in Patients (Pts) With Advanced Non-Small Cell Lung Cancer (aNSCLC) Previously Treated With an Immune Checkpoint Inhibitor (ICI): Results From Cohorts 7 and 20 of the COSMIC-021 Study

Oral

Abstract 9005
Fri 3 Jun

2:24- 2:36 PM

Lung Cancer – Non-Small Cell Metastatic

Suárez

RCC

Association between depth of response and clinical outcomes: exploratory analysis in patients with previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 9ER

Oral

Abstract 4501
Fri 3 Jun

2:57- 3:09 PM

GU Cancer – Kidney and Bladder

Pal

Urothelial Carcinoma

Cabozantinib (C) in Combination With Atezolizumab (A) in Urothelial Carcinoma (UC): Results From Cohorts 3, 4, 5 of the COSMIC-021 Study5

Oral

Abstract 4504

Fri 3 Jun

3:57 PM – 4:09 PM

GU Cancer – Kidney and Bladder

Capdevila

RAI-R DTC

Cabozantinib versus placebo in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-targeted therapy: outcomes in prespecified subgroups based on histology subtypes

Poster

Abstract 6081

Mon Jun 6

1:15-4:15 PM

Head & Neck Cancer

Hernando

RAI-R DTC

Cabozantinib (C) versus placebo (P) in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-targeted therapy: outcomes in prespecified subgroups based on prior VEGFR-targeted therapy

Poster

Abstract 6083

Mon Jun 6

1:15-4:15 PM

Head & Neck Cancer

About non-small cell lung cancer (NSCLC)
Lung cancer is one of the leading causes of cancer death globally.6 There are broadly two different groups of lung cancer – NSCLC and SCLC (small cell lung cancer). NSCLC accounts for around 80-85% of all cases.7 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. These subtypes, which start from different types of lung cells are grouped together as NSCLC because their treatment and prognoses are often similar.7

About renal cell carcinoma (RCC)
There were over 430,000 new cases of kidney cancer diagnosed worldwide in 2020.8 Of these, RCC is the most common type of kidney cancer, accounting for approximately 90% of cases.9,10 It is almost twice as common in men, and male patients account for over two thirds of deaths.9 If detected in the early stages, the five-year survival rate is high, but for patients with or late-stage metastatic RCC the survival rate is much lower, around 12%, with no identified cure for this disease.11,12

About radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC)
In 2020, over 580,000 new cases of thyroid cancer were diagnosed worldwide.13 Thyroid cancer is the ninth most commonly occurring cancer globally and incidence is three times higher in women than in men, with the disease representing one in every 20 cancers diagnosed among women.13 While cancerous thyroid tumors include differentiated, medullary and anaplastic forms, differentiated thyroid cancer (DTC) makes up about 90 to 95% of cases.14,15 DTC is typically treated with surgery, followed by ablation of the remaining thyroid tissue with radioactive iodine (RAI), but approximately 5 to 15% of cases are resistant to RAI treatment.16 Patients who develop RAI-R DTC have a poor prognosis with an average estimated survival of three to five years.17

About the COSMIC-021 trial18
COSMIC-021 is a multicenter, Phase Ib, open-label study that was divided into two parts: a dose-escalation phase and an expansion cohort phase. In the expansion phase, the trial enrolled 23 cohorts in 12 tumor types: NSCLC, RCC, UC, castration-resistant prostate cancer, hepatocellular carcinoma, triple-negative breast cancer, epithelial ovarian cancer, endometrial cancer, gastric or gastroesophageal junction adenocarcinoma, colorectal adenocarcinoma, head and neck cancer, and DTC. Exelixis is the study sponsor of COSMIC-021. Both Ipsen and Takeda Pharmaceutical Company Limited (Takeda) have opted in to participate in the trial and are contributing to the funding for this study under the terms of the companies’ respective collaboration agreements with Exelixis. Roche is providing atezolizumab for the trial.

About the CheckMate -9ER trial19
CheckMate -9ER was an open-label, randomized, multi-national Phase III trial evaluating people living with previously untreated advanced or metastatic RCC. A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to Cabometyx plus nivolumab (n= 323) versus sunitinib (n=328). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and objective response rate (ORR). The primary efficacy analysis compared the doublet combination versus sunitinib in all randomized patients. The trial was sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda.

About the COSMIC-311 trial20
COSMIC-311 was a multicenter, randomized, double-blind, placebo-controlled Phase III trial that enrolled 258 patients at 164 sites globally. Patients were randomized in a 2:1 ratio to receive either Cabometyx 60 mg or placebo once-daily. The primary endpoints were progression-free survival in the intention-to-treat population as well as objective response rate in the first 100 randomly assigned patients (objective response rate intention-to-treat [OITT] population), both evaluated by a blinded independent radiology committee. Additional endpoints included safety, overall survival and quality of life. Exelixis is the sponsor, and Ipsen is co-funding the COSMIC-311 trial.

About Cabometyx (cabozantinib)
Outside the United States and Japan, Cabometyx is currently approved in 60 countries, including in the European Union (E.U.), Great Britain, Norway, Iceland, Australia, New Zealand, Switzerland, South Korea, Canada, Brazil, Taiwan, Hong Kong, Singapore, Macau, Jordan, Lebanon, the Russian Federation, Ukraine, Turkey, the United Arabic Emirates (U.A.E.), Saudi Arabia, Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, the Dominican Republic, Ecuador, Thailand, Malaysia, Colombia, Egypt and Kazakhstan for the treatment of advanced renal cell carcinoma (RCC) in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy; in the E.U., Great Britain, Norway, Iceland, Canada, Australia, New Zealand, Brazil, Taiwan, Hong Kong, Singapore, Lebanon, Jordan, the Russian Federation, Ukraine, Turkey, the U.A.E., Saudi Arabia, Israel, Serbia, Mexico, Chile, Peru, Panama, Guatemala, the Dominican Republic, Ecuador, Thailand, Egypt, Malaysia and Kazakhstan for previously untreated intermediate- or poor-risk advanced RCC; and in the E.U., Great Britain, Norway, Iceland, Canada, Australia, Switzerland, Saudi Arabia, Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, the Russian Federation, Ukraine, Turkey, Lebanon, the U.A.E., Peru, Panama, Guatemala, Chile, the Dominican Republic, Ecuador, Thailand, Brazil, New Zealand, Egypt, Malaysia and Kazakhstan for hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib. Cabometyx is approved in combination with nivolumab as first-line treatment for people living with advanced RCC, in the E.U., Great Britain, Norway, Iceland, Switzerland, Canada, Taiwan, Singapore, the U.A.E., Australia, Chile, Israel, Thailand, Malaysia, South Korea, Saudi Arabia, the Russian Federation, Brazil and Kazakhstan. Cabometyx is also approved in the E.U., Great Britain and Canada as a monotherapy for the treatment of adult patients with locally advanced or metastatic differentiated thyroid carcinoma (DTC), refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy. In the U.S., Cabometyx tablets are approved for the treatment of people living with advanced RCC; for the treatment of people living with HCC who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adults and pediatric patients 12 years of age and older with locally advanced or metastatic DTC.

The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC)* and in the U.S. Prescribing Information (USPI).

Ipsen has exclusive rights for the commercialization of Cabometyx outside the U.S. and Japan. Cabometyx is marketed by Exelixis in the U.S. and by Takeda in Japan. Cabometyx is a registered trademark of Exelixis.

On May 26, 2022 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage biopharmaceutical company on a mission to deliver transformative therapies for rare cancers, reported two abstracts have been accepted into the program for the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) being held June 3-7, 2022, in Chicago and online (Press release, Sierra Oncology, MAY 26, 2022, View Source [SID1234615118]). An abstract presenting the full data from the pivotal phase 3 MOMENTUM study in myelofibrosis patients who are symptomatic and anemic has been selected for an oral presentation on June 7. An additional subset analysis from the trial evaluating safety and efficacy for patients with low platelet counts has been selected for poster presentation.

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"Receiving an oral presentation at ASCO (Free ASCO Whitepaper) for our pivotal Phase 3 study data—which demonstrated that momelotinib achieved statistically significant and clinically important efficacy across all prespecified and key secondary endpoints—is truly a momentous occasion for Sierra Oncology. Further, we are excited to present a subset analysis in a poster presentation examining the use of momelotinib in thrombocytopenic patients with platelet counts as low as 25 x 109/L," said Barbara Klencke, MD, Chief Medical Officer at Sierra Oncology. "Together, these abstracts demonstrate the true potential use of momelotinib as the treatment of choice across a range of myelofibrosis patients who are symptomatic and cytopenic, including those with anemia and thrombocytopenia."

Abstract: 7002: MOMENTUM: Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic and Anemic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor

The primary and all key secondary results, as well as safety data, from the MOMENTUM pivotal Phase 3 trial of momelotinib will be presented in an oral presentation by Ruben Mesa, MD, co-Principal Investigator of the study. Key data to be presented include:

Primary Endpoint of Total Symptom Score (TSS) of >50%: 25% in the MMB arm vs. 9% in the control arm (p=0.0095)
Secondary Endpoint of Transfusion Independence (TI): 31% in the MMB arm vs. 20% in the control arm (one-sided p=0.0064; non-inferiority)
Secondary Endpoint of Splenic Response Rate (SRR) >35%: 23% in the MMB arm vs. 3% in the control arm (p=0.0006)
SRR of >25% was 40% in the MMB arm and 6% in the control arm
A trend toward improved overall survival is demonstrated in the MMB arm based on data up to Week 24 (p=0.0719) and overall (p=0.3510)
The rate of Grade 3 or worse adverse events in the randomized treatment period was 54% in the MMB arm and 65% in the control arm. Serious treatment emergent adverse events were 35% in the MMB arm and 40% in the control arm. The most frequent non-hematologic adverse events were diarrhea, nausea, asthenia, pruritis and increased blood creatinine
Mean baseline characteristics for all patients were TSS of 27, Hemoglobin (Hgb) of 8 g/dL and platelet count of 145 x 109/L
Abstract 7061: Thrombocytopenic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor in a Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) [MOMENTUM]

Abstract 7061 will highlight an analysis of MOMENTUM patients with baseline platelet counts as low as 25 x 109/L on study endpoints, including Week 24 TSS reduction of >50% from baseline, transfusion independence rates, and SRR of >35% from baseline. Results to be presented include:

Of the 195 patients enrolled in the MOMENTUM study, 124, 100 and 31 patients had baseline platelet counts of less than 150, 100, and 50 x 109/L, respectively.
In patients with baseline platelets <100 x 109/L (MMB: n=66; DAN: n=34): TSS responder proportion was 29% in the MMB arm and 15% in the control arm; TI response proportion was 27% in the MMB arm and 21% in the control arm; SRR was 20% in the MMB arm and 6% in the control arm
In patients with baseline platelets <50 x 109/L (MMB: n=18; DAN: n=13): TSS responder proportion was 22% in the MMB arm and 8% in the control arm; TI response proportion was 17% in the MMB arm and 15% in the control arm; SRR was 22% in the MMB arm and 0% in the control arm
The broader thrombocytopenic subgroup with baseline platelets <150 x 109/L demonstrated similar efficacy and safety as described in the published abstract
In patients with baseline platelets below 50 x 109/L, mean platelet levels remained stable over time in both the MMB and control arms
Overall Survival directionally favored the MMB arm, consistent with the survival results in the intent-to-treat population
The proportion of patients who experience Grade 3 or higher treatment-emergent adverse events were comparable between the study arms
Mean baseline characteristics for patients with baseline platelets <100 x 109/L included TSS of 28 and 25 and Hgb of 8.1 and 7.8 g/dL for the MMB and control arms, respectively.
In thrombocytopenic, symptomatic and anemic patients with myelofibrosis, including those with platelets as low as 25 x 109/L, momelotinib was administered safely and demonstrated improvements in symptom responses, transfusion independence rates and spleen responses as compared to danazol. Consistent with the overall intent-to-treat MOMENTUM population, platelets levels remained stable over time, survival favored momelotinib versus danazol, and the safety profile was generally maintained in thrombocytopenic myelofibrosis patients receiving momelotinib.

Presentation Details

Abstract 7002
Title: MOMENTUM: Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic and Anemic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor
Presenter: Ruben Mesa, MD, FACP, Executive Director of the Mays Cancer Center, home to UT Health San Antonio, MD Anderson Cancer Center
Session Title: Oral Abstract Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Presentation Date and Time: Tuesday, June 7, 2022, 10:33 am CT

Abstract 7061
Title: Thrombocytopenic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor in a Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) [MOMENTUM]
Presenter: Aaron Gerds, MD, MS, Taussig Cancer Institute, Cleveland Clinic
Session Title: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Session Date and Time: Saturday, June 4, 2022, 8:00 am – 11:00 am CT

About Momelotinib
Momelotinib is a potent, selective and orally bioavailable ACVR1 / ALK2, JAK1, JAK2 inhibitor under investigation for the treatment of myelofibrosis in symptomatic, anemic patients previously treated with an approved JAK inhibitor. More than 1,200 subjects have received momelotinib since clinical studies began in 2009, including approximately 1,000 patients treated for myelofibrosis, several of whom remain on treatment for over 11 years. Momelotinib is the first and only JAK inhibitor to demonstrate positive data for all key hallmarks of the disease—symptoms, splenic response and anemia.

About Myelofibrosis
Myelofibrosis is a rare blood cancer that results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia. From prior studies with momelotinib, we know approximately half of myelofibrosis patients are moderately to severely anemic when eligible for JAK inhibitor treatment. Furthermore, currently approved JAK inhibitors only address symptoms and splenomegaly and are myelosuppressive. This can lead to worsening anemia, resulting in dose reductions that potentially reduce treatment effect.

About the Pivotal MOMENTUM Clinical Trial
MOMENTUM is a global, randomized, double-blind Phase 3 clinical trial of momelotinib versus danazol in patients with myelofibrosis who were symptomatic and anemic, and had been previously treated with an FDA-approved JAK inhibitor. The study was designed to evaluate the safety and efficacy of momelotinib for the treatment and reduction of the key hallmarks of disease: symptoms, blood transfusions (due to anemia) and splenomegaly (enlarged spleen).

The primary endpoint of the study is Total Symptom Score (TSS) reduction of >50% over the 28 days immediately prior to the end of Week 24 compared to baseline TSS, using the Myelofibrosis Symptom Assessment Form (MFSAF). Secondary endpoints included Transfusion Independence (TI) rate for >12 weeks immediately prior to the end of Week 24 with Hgb levels ≥ 8 g/dL, and Splenic Response Rate (SRR) based on splenic volume reduction of >35% at Week 24. The study enrolled 195 patients based on a planned 180 patients across 21 countries.

Danazol was selected as the treatment comparator given its use to ameliorate anemia in patients with myelofibrosis, as recommended by National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) guidelines. Patients were randomized 2:1 (MMB n = 130 and DAN n = 65) to receive either momelotinib or danazol. After 24 weeks of treatment, patients on danazol were allowed to crossover to receive momelotinib. Early cross-over to momelotinib was available for confirmed symptomatic splenic progression.

On May 26, 2022 Novocure (NASDAQ: NVCR) reported it has entered into a clinical trial collaboration agreement with MSD, a tradename of Merck & Co., Inc., Rahway, NJ, USA, to study the use of Tumor Treating Fields (TTFields) concomitant with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of patients with newly diagnosed glioblastoma (GBM) (Press release, NovoCure, MAY 26, 2022, View Source [SID1234615117]). This is the second clinical collaboration between Novocure and MSD.

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"We are excited to collaborate again with global oncology leader, MSD, in the pursuit of extending survival in some of the most aggressive forms of cancer," said William Doyle, Novocure’s Executive Chairman. "EF-41/Keynote D58 will build on encouraging preliminary data from the 2-THE-TOP phase 2 pilot study and will further explore recently published data suggesting the potential for a therapeutic benefit when TTFields are used together with immunotherapy due to TTFields’ downstream immune system activation and anti-tumor cell response. Through the EF-41/Keynote D58 trial, we hope to identify a potential new treatment option for solid tumor cancers and we are thrilled at the prospect of improving outcomes for patients in need."

Novocure and MSD plan to conduct a double-blind, placebo-controlled study of TTFields concomitant with KEYTRUDA and maintenance temozolomide (TMZ) versus TTFields together with placebo and maintenance TMZ for the treatment of adult patients with newly diagnosed GBM. Novocure intends to engage FDA in the near term in a pre-submission discussion regarding the details of the agreed upon study.

ABOUT 2-THE-TOP

The EF-41/Keynote D58 trial will build on encouraging preliminary data from the 2-THE-TOP phase 2 pilot study. The 2-THE-TOP trial is an investigator-initiated, phase 2 pilot trial evaluating the use of TTFields therapy together with pembrolizumab and chemotherapy (temozolomide) for the treatment of 26 adult patients with newly diagnosed GBM. In March 2022, updated data from the ongoing 2-THE-TOP study was presented at the World Federation of Neuro-oncology Societies (WFNOS) 2022 Quadrennial Meeting, comparing outcomes for 26 patients in the 2-THE-TOP study versus a historical, matched-control group of 26 patients from the TTFields plus temozolomide arm of the phase 3 pivotal EF-14 clinical trial. Patients in the 2-THE-TOP trial displayed median progression-free survival (primary endpoint) of 12.1 months and median overall survival of 25.2 months, which are based on a median follow-up time of 16.8 months. Additionally, 193,760 peripheral blood mononuclear cells were sequenced in 12 patients before pembrolizumab was administered and detected robust post-TTFields T cell activation in 11 of 12 patients via the T1IFN trajectory with a strong correlation with the TCRαβ clonal expansion Simpson index (Spearman coefficient r=-0.8, P=0.014).

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division. Fundamental scientific research extends across more than two decades and, in all preclinical research to date, TTFields have demonstrated a consistent anti-mitotic effect. TTFields therapy is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields therapy has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 24,000 patients have been treated with TTFields therapy.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On May 26, 2022 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, reported that the European Commission (EC) has granted conditional marketing authorization of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel in December 2017 (Press release, Legend Biotech, MAY 26, 2022, View Source [SID1234615116]).

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CARVYKTI is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen (BCMA)-targeting single domain antibodies.1 CAR-T therapy is specifically developed for each individual patient, and it is administered as a single infusion.1,2

"The approval of CARVYKTI by the European Commission marks Legend’s first approval in the region and is a significant milestone as we advance our commitment to bring innovative cell therapies to patients with the highest unmet need," said Ying Huang, Ph.D., Chief Executive Officer of Legend Biotech. "The CARTITUDE-1 data showed that CARVYKTI provides the potential for long, treatment-free intervals for heavily pre-treated patients, and is a valuable treatment option for patients with multiple myeloma. We look forward to working with Janssen to bring this new option to patients across Europe."

This approval was supported by the pivotal CARTITUDE-1 study, including patients who had received a median of six prior treatment regimens (range, 3-18), and had previously received an IMiD, PI and anti-CD38 monoclonal antibody.3 Findings showed that at a median duration of 18 months follow-up (range, 1.5-30.5), a one-time treatment with cilta-cel resulted in deep and durable responses, with 98 percent (95 percent confidence interval [CI], 92.7-99.7) of patients with RRMM responding to therapy (98 percent overall response rate [ORR] (N=97)).3,4 Notably, 80 percent of the patients achieved stringent complete response (sCR), a measure in which a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment.3

The safety of cilta-cel was evaluated in 179 adult patients across two open-label clinical trials (MMY2001 and MMY2003). The most common adverse reactions (≥20 percent) were neutropenia (91 percent), cytokine release syndrome (CRS) (88 percent), pyrexia (88 percent), thrombocytopenia (73 percent), anemia (72 percent), leukopenia (54 percent), lymphopenia (45 percent), musculoskeletal pain (43 percent), hypotension (41 percent), fatigue (40 percent), transaminase elevation (37 percent), upper respiratory tract infection (32 percent), diarrhea (28 percent), hypocalcemia (27 percent), hypophosphatemia (26 percent), nausea (26 percent), headache (25 percent), cough (25 percent), tachycardia (23 percent), chills (23 percent), encephalopathy (22 percent), decreased appetite (22 percent), oedema (22 percent), and hypokalemia (20 percent).4

"There continues to be an unmet need for patients with relapsed or refractory multiple myeloma who have exhausted existing treatment options. Data from the CARTITUDE-1 trial have shown that cilta-cel provides deep and durable responses for heavily pre-treated patients. Today’s approval by the European Commission reinforces the potential of this new treatment option for multiple myeloma patients in Europe," said Hermann Einsele, Full Professor of Internal Medicine and Director of the Medizinische Klinik und Poliklinik II of the Julius Maximilian University, Würzburg, Germany.*

As a highly personalized medicine, where a patient’s own T-cells are reprogrammed to target and kill cancer cells, administration of CAR-T therapy requires extensive training, preparation, and certification to ensure the highest quality product and experience for patients.2 Through a phased approach, Legend Biotech’s strategic partner, Janssen, will work diligently to activate a limited network of certified treatment centers and will aim to increase availability of cilta-cel across Europe, in an effort to provide oncologists and patients with treatment in a reliable manner.

This EC Marketing Authorization follows the approval of CARVYKTI by the U.S. Food and Drug Administration (FDA) on February 28, 2022.

*Hermann Einsele, M.D., FRCP has not been paid for contributing to this press release.

About CARVYKTI (ciltacabtagene autoleucel; cilta-cel)

CARVYKTI is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA.4 BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells.4 The CARVYKTI CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA.4 Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.4

In December 2017, Legend Biotech Corporation entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel.5

In April 2021, Legend announced the submission of a Marketing Authorisation Application to the European Medicines Agency seeking approval of cilta-cel for the treatment of patients with relapsed or refractory multiple myeloma. In addition to U.S. Breakthrough Therapy Designation granted in December 2019, cilta-cel also received Breakthrough Therapy Designation in China in August 2020. In February 2019, cilta-cel received Orphan Drug Designation from the U.S. FDA from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020. In May 2022, the Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained, on the basis of clinical data demonstrating improved and sustained complete response rates following treatment.6 Cilta-cel was approved the U.S. Food and Drug Administration (FDA) in February 2022.5

About CARTITUDE-1

CARTITUDE-1 (NCT03548207)7 is an ongoing Phase 1b/2, open-label, single arm, multi-center trial evaluating cilta-cel for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received at least three prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody. Of the 97 patients enrolled in the trial, 99 percent were refractory to the last line of treatment and 88 percent were triple-class refractory, meaning their cancer did not respond, or no longer responds, to an IMiD, a PI and an anti-CD38 monoclonal antibody.4

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.8 In Europe, it is estimated that more than 50,900 people were diagnosed with multiple myeloma in 2020, and approximately 32,500 patients died.9 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.10 Although treatment may result in remission, unfortunately, patients will most likely relapse.11 Patients who relapse after treatment with standard therapies, including protease inhibitors, immunomodulatory agents, and an anti-CD38 monoclonal antibody, have poor prognoses and few treatment options available.12,13