On May 26, 2022 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported additional exploratory data for poziotinib in non-small cell lung cancer (NSCLC) patients harboring HER2 exon 20 insertion mutations at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago from June 3-7 (Press release, Spectrum Pharmaceuticals, MAY 26, 2022, View Source [SID1234615103]).

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In poziotinib treated patients with advanced NSCLC harboring HER2 exon 20 insertion mutations, baseline ctDNA presence was associated with the tumor tissue genotyping with a concordance of 95%. In patients who responded to treatment, reduced ctDNA levels were associated with tumor mass reduction by central imaging. Increases in ctDNA were observed prior to confirmation of tumor escape, or disease progression.

"This early data suggests that a reduction in ctDNA may be a predictor of response to treatment with poziotinib," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "We are encouraged by these findings and look forward to further investigate ctDNA as a potential predictive biomarker of poziotinib treatment response."

Poziotinib is currently under review by the U.S. Food and Drug Administration (FDA) with a PDUFA date of November 24, 2022 and has received Fast Track designation from the agency.

Session title and information for the poster is listed below and is available on the ASCO (Free ASCO Whitepaper) online itinerary planner.

Circulating tumor DNA (ctDNA) in HER2 exon 20 insertion mutations and responses in NSCLC HER2 exon 20 insertion treated with poziotinib
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Session Date and Time: Sunday, June 5, 2022, 8-11 a.m. CDT, 6-9 a.m. PT
Location: McCormick Place, Chicago IL
Abstract: 3051 / Poster: 43

Copies of the presentation will be available on Spectrum’s website at View Source following presentation at the meeting.

About the ZENITH20 Clinical Trial

The ZENITH20 study is a multicenter, open-label Phase 2 trial, evaluating poziotinib in patients with advanced or metastatic NSCLC patients with EGFR or HER2 exon 20 insertion mutations. The trial is comprised of 7 independent cohorts. Cohorts 1 – 4 were each independently powered for a pre-specified statistical hypothesis with a primary endpoint of ORR, or objective response rate evaluated by independent review committee (RECIST v1.1). Cohorts 5 – 7 are exploratory. Secondary outcome measures are disease control rate, duration of response, progression-free survival, and safety and tolerability. The patients’ quality of life is also measured and assessed throughout. Cohort 4 includes first-line NSCLC patients with HER2 exon 20 mutations and cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations.

About Poziotinib

Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. HER2 exon 20 insertion mutations are a rare subset accounting for approximately 2-4% in NSCLC. There is no approved therapy for either treatment-naïve or previously treated NSCLC with HER2 exon 20 insertion mutations. The company holds an exclusive license from Hanmi Pharmaceutical to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by the company and Hanmi in several mid-stage trials in multiple solid tumor indications.

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 Foundation Medicine, Inc., a pioneer in molecular profiling for cancer, reported that the company and its collaborators will present a total of 26 abstracts at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held virtually and in person in Chicago from June 3-7, 2022 (Press release, Foundation Medicine, MAY 26, 2022, View Source [SID1234615135]).

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Presentations focus on the power of genomic research to provide physicians and researchers with the latest insights on innovative treatment strategies for patients, including those with early-stage cancers, and cancers with rare or complex alterations. Highlights of this data include:

Research demonstrating the value of FoundationOneLiquid CDx blood-based comprehensive genomic profiling (CGP) to support physicians in finding the answers they need to make informed treatment decisions for their patients, such as detecting resistance alterations, and to provide researchers with genomic insights to aid in the discovery and utilization of new biomarkers
Several studies from Foundation Medicine researchers and collaborators at prominent cancer institutions highlighting the broad utility of real-world genomic data from the Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB) and the FoundationCore Genomic Database. These studies explore:
Opportunities to use these databases to achieve more equity in cancer care, such as using real-world data to reveal ancestry-associated differences in genomic alterations in non-small cell lung cancer (NSCLC)
Areas to bring CGP into earlier stages of disease to assist in curative intent treatment planning or selection
The potential value of the predictive complex biomarkers tumor mutational burden (TMB) and microsatellite instability (MSI) to aid in consideration of first line immunotherapy in metastatic endometrial cancer
The ability of diverse MET alterations to support treatment planning in NSCLC
"At Foundation Medicine, we provide doctors and researchers with tools to help them find answers and take action on treatment options for patients across cancer types and stages. At this year’s ASCO (Free ASCO Whitepaper), we will demonstrate the expanded capacity of our tests to detect actionable complex biomarkers and alterations in earlier stages of cancer to support care decisions for patients," said Priti Hegde, PhD, chief scientific officer at Foundation Medicine. "We are proud of our many collaborations on this research with partners across the oncology community. These collaborations reinforce Foundation Medicine’s role as an essential partner with the scientific expertise and real-world data to support efficient progress for equitable patient care."

The Value of Liquid Biopsy in Identifying Actionable Alterations

LCMC LEADER neoadjuvant screening trial: LCMC4 evaluation of actionable drivers in early stage lung cancers. Abstract #TPS8596.

In collaboration with the Lung Cancer Research Foundation, the Lung Cancer Mutation Consortium, and Memorial Sloan Kettering Cancer Center, this Trial in Progress abstract details the umbrella trial design of the LCMC4 Evaluation of Actionable Drivers in EaRly-Stage Lung Cancer (LEADER) clinical trial. Foundation Medicine’s tissue-based CGP test, FoundationOneCDx, and its blood-based CGP test, FoundationOneLiquidCDx, will both be used in the LEADER trial to screen for 10 actionable driver mutations in 1,000 patients with high-risk, resectable NSCLC who are candidates for neoadjuvant therapy. Results will enable selection of neoadjuvant therapy and enrollment onto independent therapeutic trials with genomically matched neoadjuvant treatment, standard therapies, or other trials if no driver is detected.

CtDNA shed as a tool to select immune checkpoint inhibitors (ICPI) with or without chemotherapy for patients (pts) with advanced non-small cell lung cancer (aNSCLC). Abstract #9045.

Using the CGDB, this study with Gustave Roussy Cancer Center investigated circulating tumor DNA (ctDNA) shed as an indicator to support treatment selection for patients with advanced NSCLC. Researchers found that elevated plasma tumor fraction (TF) can identify patients at risk of early progression on immune checkpoint inhibitors (ICPI) who may benefit from chemotherapy in addition to an ICPI. In patients with low/intermediate TF, the study found that outcomes on ICPIs alone are similar to those receiving both chemotherapy and ICPI treatment, suggesting TF’s ability as a non-invasive tool to identify patients for single-agent ICPI.

Genomic landscape of acquired resistance to targeted therapies in patients with solid tumors: a study from the National Center for Precision Medicine (PRISM). Abstract #3016.

Researchers from Gustave Roussy Cancer Center and Institut Bergonié set up a study using FoundationOneLiquid CDx to detect ctDNA in an effort to characterize the landscape of secondary resistance mechanisms in patients with solid tumors. While many targeted therapies are approved for treatment in solid tumors, acquired resistance to these therapies remains as a barrier limiting the ultimate effectiveness of these treatments. Researchers reported that polyclonal secondary genomic alterations represent a frequent clinical resistance mechanism that may explain the low rate of sustained complete remission for patients treated with targeted therapies.

The Power of Real-World Genomic Data to Shape the Future of Cancer Care

A real-world (rw) evidence study quantifying the clinical value of multi-gene testing in early-stage lung adenocarcinoma (LUAD). Abstract #8525.

In collaboration with Cleveland Clinic Cancer Center and Flatiron Health, this study used the CGDB to assess the potential value of CGP in early-stage lung adenocarcinoma (LUAD). Researchers found that CGP of early-stage LUAD can identify EGFR, ALK, ROS1, RET and other drivers and enable appropriate selection of targeted therapies and timely use of effective first line therapy at recurrence. By avoiding the use of ICPIs in patients unlikely to respond, CGP could represent a way to avoid ineffective treatment and risk of tyrosine kinase inhibitor (TKI)-associated toxicity.

Biomarker associations of immune checkpoint inhibitor versus chemotherapy effectiveness in first-line metastatic endometrial carcinomas: A real-world study. Abstract #5596.

Using real world data from the CGDB, this study in partnership with the Yale School of Medicine evaluated TMB greater than 10 mutations per megabase and MSI-high as predictive biomarkers for ICPI benefit in comparison to standard of care chemotherapy in first line metastatic endometrial cancer (mEC). More favorable time to next treatment and overall survival were observed on ICPI versus chemotherapy in first line treatment among those with high TMB and/or MSI-high, but not those without. The results of this study suggest that a randomized controlled trial in this setting using these biomarkers has a favorable chance of success to develop a chemotherapy-sparing first line option for patients with mEC.

Clinical and genomic characteristics of pts with durable benefit from immune checkpoint inhibitors (ICPI) in advanced non-small cell lung cancer (aNSCLC). Abstract #9048.

In collaboration with Dana-Farber Cancer Institute, this study queried the CGDB to better understand patients with advanced NSCLC who had a durable response to ICPIs. The two-year mark has increasingly become a milestone in progression-free patients with advanced NSCLC, with a subset experiencing ongoing disease control even after discontinuing active treatment. In a cohort of 4,030 advanced NSCLC patients, 4.6% were free of progression or treatment failure at 24 months, with a median overall survival of almost 5 years. 41% of those patients stopped immunotherapy usage before the two-year mark. Researchers also found that elevated TMB was associated with durable benefit on ICPIs, as well as prolonged progression-free survival after the 2-year mark and deserves further investigation as a biomarker for prolonged benefit from ICPIs in advanced NSCLC.

Ancestry-based differences in gene alterations in non-small cell lung cancer: Real-world data using genetic ancestry analysis. Abstract #9125.

In this study, researchers investigated alteration prevalence in a large real-world NSCLC cohort, stratified by genetic ancestry. Together with Juntendo University Graduate School of Medicine and others, the study looked at FoundationCore, Foundation Medicine’s robust real-world dataset, to reveal ancestry-associated differences in genomic alterations in NSCLC. Age and sex were also associated with differences in prevalence of gene alterations and immunotherapy-associated biomarkers, such as high TMB status.

Real-world (rw) analysis of quantitative MET copy number (CN) as a biomarker in advanced NSCLC (aNSCLC). Abstract #9123.

Researchers used real-world data from the CGDB to explore the genomic landscape of MET amplification in NSCLC and its association with outcomes to MET TKIs. In partnership with the University of Colorado, CGP results from 64,521 tissue and 5,177 blood-based NSCLC samples were queried for MET amplification, which was detected in 3.3% of tissue samples and 3.2% of high TF blood samples. MET amplification was found to be associated with response to MET TKIs. In TKI-naïve patients, MET copy number was negatively correlated with the presence of a concurrent NSCLC driver, suggesting that further studies evaluating MET copy number as a predicative biomarker for MET TKIs, and as an indicator of MET dependence to aid therapy section, are warranted.

Activating MET kinase domain mutations define a novel molecular subtype of non-small cell lung cancer that is clinically targetable with the MET inhibitor elzovantinib (TPX-0022). Abstract #9124.

In this study conducted in partnership with Dana-Farber Cancer Institute and Turning Point Therapeutics, researchers investigated a novel, actionable subtype of NSCLC characterized by activating MET tyrosine kinase domain (MET-TKD) mutations in the absence of METex14 mutations. Looking at a multi-institutional dataset of cancers that underwent genomic profiling, including FoundationCore, researchers found that potentially actionable MET-TKD mutations represent a novel genomic subtype in 0.6-0.9% of NSCLC and occur in the absence of other known drivers in a subset of cases.

The following is a list of select abstracts that will be presented at the meeting. To access all abstracts being presented by Foundation Medicine and its collaborators, please visit: meetinglibrary.asco.org.

On May 26, 2022 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that the company will present a Trials in Progress poster highlighting the Phase I/II clinical trial of BT7480, a novel, fully synthetic Bicycle TICA targeting Nectin-4 and agonizing CD137, at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL on June 3-7, 2022 (Press release, Bicycle Therapeutics, MAY 26, 2022, View Source [SID1234615071]).

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Poster Presentation Details

Title: A Combined Phase I/II Study of a Novel Bicycle Tumor-targeted Immune Cell Agonist BT7480 in Patients with Nectin-4 Associated Advanced Malignancies
Abstract #: TPS2689
Poster #: 332b
Presenter: Kyriakos P. Papadopoulos, START San Antonio
Session Title: Development Therapeutics – Immunotherapy
Date/Time: Sunday, June 5, 2022 at 9:00 a.m. ET

The poster will be available on the Publications section of bicycletherapeutics.com following the presentation.

On May 26, 2022 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported additional efficacy data from the pivotal SORAYA study evaluating mirvetuximab soravtansine (mirvetuximab) monotherapy in patients with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer who have been previously treated with Avastin (bevacizumab) and an integrated safety summary of single-agent mirvetuximab across multiple studies in patients with FRα-positive recurrent ovarian cancer (Press release, ImmunoGen, MAY 26, 2022, View Source [SID1234615088]). These findings will be highlighted in two posters at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held June 3-7, 2022. The data from SORAYA have been selected for the Best of ASCO (Free ASCO Whitepaper) Program.

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

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"Treatment options remain limited for patients with platinum-resistant ovarian cancer, particularly for those who have received prior bevacizumab, and are associated with low response rates, short durations of response, and considerable toxicities," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "We believe these data further reinforce mirvetuximab’s potential to become a new standard of care in this population. With our biologics license application accepted and filed by FDA with Priority Review, we look forward to bringing mirvetuximab to patients with the most urgent need later this year."

CHARACTERIZATION OF ANTI-TUMOR ACTIVITY IN THE SORAYA STUDY
SORAYA enrolled 106 platinum-resistant ovarian cancer patients with high FRα expression who have been previously treated with 1 to 3 prior systemic treatments, at least one of which included bevacizumab. The primary endpoint was confirmed objective response rate (ORR) as assessed by investigator. Secondary endpoints included duration of response (DOR) as assessed by investigator, CA-125 response, safety and tolerability, progression-free survival (PFS), overall survival (OS); ORR, DOR, and PFS by blinded independent central review were sensitivity analyses. Data from SORAYA were first presented at the Society of Gynecologic Oncology (SGO) 2022 Annual Meeting; the updated analyses to be presented at ASCO (Free ASCO Whitepaper) are based on the 120-day cut-off date of April 29, 2022.

ORR by investigator was 32.4% (95% confidence interval [CI]: 23.6%, 42.2%), including 5 complete responses. Median time to response was 1.5 months (range 1.0 to 5.6) and 71.4% of patients demonstrated tumor reduction.
The disease control rate (DCR), defined as complete response (CR), partial response, or stable disease maintained for ≥12 weeks, was 51.4%.
The median DOR was 6.9 months (95% CI: 5.6, 9.7) by investigator, with 5 responders continuing on mirvetuximab as of April 29, 2022.
The median PFS assessed by investigator was 4.3 months (95% CI: 3.7, 5.2).
The preliminary median OS was 13.8 months, with 54% of the evaluable patient population event-free.
In the sensitivity analyses by blinded independent central review, outcomes were similar: ORR 30.2% (95% CI: 21.3%, 40.4%) with 6 CRs; mDOR not reached (95% CI: 5.0, NR); mPFS 5.5 months (95% CI: 3.8, 6.9).
In responders, depth and duration of response did not appear to be affected by dose reductions.
Mirvetuximab was well-tolerated, consistent with previous studies. The most common treatment-related adverse events (TRAE) included blurred vision (41% all grade, 6% grade 3+), keratopathy (29% all grade, 9% grade 3+), and nausea (29% all grade, 0% grade 3+).
TRAEs generally resolved with supportive care or, if needed, dose modifications; the discontinuation rate due to TRAEs was 9%.
Kaplan-Meier plots for PFS and OS to be included in poster.
"I believe these additional analyses from SORAYA further support mirvetuximab’s potential to become the first biomarker-directed agent indicated for patients with platinum-resistant ovarian cancer," said Ursula Matulonis, MD, Chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute, Professor of Medicine at the Harvard Medical School, and SORAYA Co-Principal Investigator. "The tumor reduction observed in over 70% of patients, along with the PFS curve and the preliminary median overall survival of 13.8 months, are impressive. If approved, I look forward to being able to offer mirvetuximab to my patients and continuing to support its further development in patients with ovarian cancer."

INTEGRATED SAFETY SUMMARY OF SINGLE-AGENT MIRVETUXIMAB SORAVTANSINE
This retrospective pooled analysis included 464 patients with FRα-positive, recurrent ovarian cancer across three studies: a Phase 1 first-in-human trial, the Phase 3 FORWARD I trial, and the pivotal Phase 3 SORAYA trial.

Mirvetuximab monotherapy has a differentiated safety profile consisting primarily of low-grade gastrointestinal and ocular events; adverse events generally resolved and were managed with supportive care and, if needed, dose modifications. The discontinuation rate due to TRAEs was 7%.
The most common TRAEs included blurred vision (42% all grade, 3% grade 3+), nausea (40% all grade, 2% grade 3+), diarrhea (33% all grade, 2% grade 3+), fatigue (31% all grade, 2% grade 3+), keratopathy (26% all grade, 3% grade 3+), and dry eye (22% all grade, 1% grade 3+).
Mirvetuximab monotherapy did not result in any corneal ulcers or perforations, and no patients had permanent ocular sequelae.
The majority of patients with ocular events did not require dose delay or dose reduction; <1% of patients discontinued mirvetuximab due to an ocular event.
"Having personally treated over 100 patients with mirvetuximab, I have helped my colleagues better understand how to manage the associated ocular events," said Kathleen Moore, Director of the Oklahoma TSET Phase I Program, Professor of the Section of Gynecologic Oncology at The University of Oklahoma College of Medicine, and MIRASOL Principal Investigator. "With prevention and mitigation strategies in place, patients presenting with ocular events have been able to complete their treatment, maintain their responses, and had no permanent sequelae from these events. These data demonstrate mirvetuximab’s differentiated safety profile and I look forward to the potential approval and launch later this year."

POSTER SESSION DETAILS
The following posters will be available on Saturday, June 4 in the ASCO (Free ASCO Whitepaper) Meeting Library:

Additional information can be found at www.asco.org.

ABOUT MIRVETUXIMAB SORAVTANSINE
Mirvetuximab soravtansine (IMGN853) is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent, to kill the targeted cancer cells.