On May 23, 2024 Mythic Therapeutics, a clinical-stage biotechnology company committed to the development of next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported that it will present initial dose escalation results from its Phase 1 KisMET-01 study evaluating its investigational cMET-targeting ADC, MYTX-011, in patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Mythic Therapeutics, MAY 23, 2024, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-to-present-data-from-phase-1-kismet-01-study-on-mytx-011-at-the-american-society-of-clinical-oncology-asco-annual-meeting [SID1234643608]).

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"We are pleased to present clinical data showcasing the potential of our lead program, MYTX-011, for patients impacted by non-small cell lung cancer," said Gilles Gallant, BPharm, Ph.D., FOPQ, Chief Development Officer at Mythic Therapeutics. "The initial dose escalation results from our ongoing KisMET-01 trial mark an important milestone in our journey, and we look forward to sharing these results with the scientific community at ASCO (Free ASCO Whitepaper)."

Details of the presentation are as follows:

Title: MYTX-011 in patients with previously treated locally advanced or metastatic NSCLC: Initial dose escalation results in the phase 1 KisMET-01 study.
Presenter: Melissa Johnson, M.D., Director, Lung Cancer Research, Sarah Cannon Research Institute
Session Title: Lung Cancer—Non-Small Cell Metastatic
Session Date and Time: Monday, June 3, 1:30 – 4:30 PM CDT
Location: Hall A | On Demand
Poster Board Number: 422
Published Abstract Number: 8558

About MYTX-011

MYTX-011, an investigational cMET-targeting ADC, leverages Mythic’s innovative FateControl technology which is designed to allow ADCs to actively navigate inside of cells, potentially increasing delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

On May 23, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, reported data from ARTISTRY-3, a clinical trial designed to evaluate the effects of less frequent intravenous dosing (LFIV) of nemvaleukin alfa (nemvaleukin), in advance of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting taking place May 31-June 4 in Chicago (Press release, Mural Oncology, MAY 23, 2024, View Source [SID1234643607]).

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Nemvaleukin, Mural’s lead candidate, is an investigational, engineered interleukin-2 (IL-2) cytokine designed to capture and expand the therapeutic benefits of high-dose native IL-2 while mitigating the cytokine’s hallmark toxicities. In ARTISTRY-1, the company sought to recapitulate the results of high-dose IL-2 by mimicking its dosing regimen with five daily intravenous (IV) infusions (days 1-5) per three-week cycle. In the ARTISTRY-3 trial, the company evaluated escalating LFIV infusions, all of which were generally well tolerated. The safety profile in all dosing schedules evaluated was consistent with nemvaleukin’s known mechanism of action, and no dose limiting toxicities were observed. Despite administering higher doses per three-week dosing cycle than in previous trials evaluating nemvaleukin with daily infusions, no new safety signals were identified. The desired pharmacodynamic (PD) effects were also seen across all evaluated doses. Expansion of antitumor CD8+ T cells and natural killer (NK cells) was observed concurrent with minimal expansion of immunosuppressive regulatory T cells (Tregs).

"Nemvaleukin demonstrated deep and durable responses in previous trials, so we sought an adapted dosing schedule to make treatment administration easier on patients and providers alike. All dosing schedules tested in ARTISTRY-3 demonstrated the desired pharmacodynamic effects, including expansion of immune-stimulating NK and CD8+ cells, with only minimal expansion of immunosuppressive Tregs. Notably, despite significantly increasing the doses, we observed no new tolerability issues compared to previous studies of nemvaleukin," said Sarina Piha-Paul, MD, Associate Professor, Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and the poster’s lead author.

After a comprehensive review of the safety, pharmacokinetics, PD, and efficacy data across the evaluated schedules and doses, and in collaboration with Mural’s safety review committee, Mural selected a 30 µg/kg dose on day 1 and day 8 as the recommended phase 2 dose. Mural believes that this seven-day window offers more time for patient recovery and allows for more flexibility both for patients and providers.

The new less frequent dosing regimen with the 30 µg/kg dose, which delivers twice the dose of nemvaleukin over a three-week cycle as the standard five-day dosing regimen, is being evaluated as both a single agent and in combination with pembrolizumab in patients with cutaneous melanoma in cohort 3 and cohort 4 of Mural’s ARTISTRY-6 clinical trial. Mural expects to provide preliminary data readouts from cohort 3 in the first half of 2025 and from cohort 4 in the second half of 2025.

"ARTISTRY-3 was designed to assess whether a more patient-friendly dosing schedule could maximize the dose of nemvaleukin without any additional tolerability issues. The data presented at ASCO (Free ASCO Whitepaper) demonstrated PD proof of mechanism and promising tolerability across all three dosing schedules. We are immediately incorporating this new dosing regimen into additional cohorts of ARTISTRY-6, our phase 2 trial of nemvaleukin," said Caroline Loew, Ph.D., CEO of Mural Oncology. "IL-2 has proven to be efficacious in cutaneous melanoma and these open label cohorts of the ARTISTRY-6 trial may yield an early signal regarding the potential of our alternative dosing both as a monotherapy therapy and in combination with pembrolizumab."

The details for the presentation are as follows, and the poster will be available on June 1 at View Source

Recommended Phase 2 Dose (RP2D) of Nemvaleukin Alfa in Patients With Advanced Solid Tumors Treated With Less Frequent Intravenous Dosing (ARTISTRY-3)

Session: Developmental Therapeutics – Immunotherapy

Date and time: June 1, 2024, 9 a.m. CDT

Abstract #: 2587

Speaker/lead author: Sarina Piha-Paul, MD

About Nemvaleukin

Nemvaleukin alfa is a novel, engineered cytokine designed to leverage antitumor effects of the IL-2 pathway while mitigating its hallmark toxicities that limit its use. Nemvaleukin selectively binds to the intermediate-affinity IL-2 receptor (IL-2R) and is sterically occluded from binding to the high-affinity IL-2R. Because of this molecular design, nemvaleukin treatment leads to preferential expansion of antitumor CD8+ T cells and natural killer cells, with minimal expansion of immunosuppressive regulatory T cells. Nemvaleukin demonstrated deep and durable responses in both monotherapy and combination therapy in ARTISTRY-1, Mural Oncology’s first Phase 1/2 trial of nemvaleukin.

Nemvaleukin is currently being evaluated in two potentially registrational trials in platinum- resistant ovarian cancer and mucosal melanoma.

About the ARTISTRY-3 Clinical Trial

ARTISTRY-3 is a Phase 1/2 open-label trial of IV nemvaleukin in patients with selected advanced solid tumors who have previously received standard of care treatment(s). The trial is evaluating doses between 10 µg/kg and 40 µg/kg across three dosing regimens: once per three-week dosing cycle; days 1 and 8 of a three-week dosing cycle; and days 1 and 4 of a three-week dosing cycle.

On May 23, 2024 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported updated clinical data for lifileucel in combination with pembrolizumab in frontline advanced melanoma, as well as translational data, for the upcoming 2024 ASCO (Free ASCO Whitepaper) Annual Meeting to be held May 31 – June 4, 2024, at McCormick Place in Chicago, IL and online (Press release, Iovance Biotherapeutics, MAY 23, 2024, View Source [SID1234643606]).

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Clinical Data in Frontline Advanced Melanoma (Cohort 1A in IOV-COM-202 Trial)
Positive results from Cohort 1A in the IOV-COM-202 trial were published in an abstract1 and will be highlighted in an upcoming oral presentation at ASCO (Free ASCO Whitepaper). Unprecedented response rates, as well as deep and durable responses, were observed in patients with frontline advanced melanoma who were naïve to immune checkpoint inhibitor (ICI) therapy. These results strongly support the ongoing Phase 3 TILVANCE-301 clinical trial.

ASCO Oral Presentation Highlights

A recent data cut included 23 patients with a median follow up of 21.7 months.2
Confirmed ORR was 65.2%, including 7 (30.4%) complete responses and 8 (34.8%) partial responses by RECIST v1.1.
All evaluable patients demonstrated regression of their target lesions.
Nearly all responses remained ongoing. The duration of response was 12+ months for 8 responders (53.3%) and 6+ months for 11 responders (73.3%).
As a one-time treatment, lifileucel’s safety profile was differentiated from continuous ICI combination regimens.
Treatment-emergent adverse events were consistent with the underlying disease and known safety profiles of pembrolizumab monotherapy, nonmyeloablative lymphodepletion, and interleukin-2.
Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "The compelling response rates, including a 30.4% complete response rate, and depth and durability of responses for lifileucel in combination with pembrolizumab strongly support our strategy in frontline advanced melanoma. Expanding TIL cell therapy into earlier treatment settings is a top priority for Iovance. The positive data are highly encouraging for the anticipated ORR results in our ongoing TILVANCE-301 trial. A planned early interim analysis of ORR, a dual primary endpoint in TILVANCE-301, may support an accelerated approval in the frontline setting, with full approval supported by progression free survival."

The clinical and safety data from Cohort 1A continue to reinforce the rationale for the TILVANCE-301 trial. TILVANCE-301 is a global, randomized, registrational Phase 3 trial to support accelerated and full U.S. approvals of lifileucel in combination with pembrolizumab in frontline advanced melanoma. In addition, the ORR endpoint in TILVANCE-301 supports full approval of lifileucel monotherapy (Amtagvi) in post-anti-PD-1 melanoma. The U.S. Food and Drug Administration (FDA) has agreed to the design of the TILVANCE-301 trial, including dual-primary endpoints of ORR and progression free survival. Iovance plans to conduct an early interim analysis of ORR as the potential basis for regulatory submission and approvals.

Iovance Presentation and Posters at ASCO (Free ASCO Whitepaper) Annual Meeting

Oral Presentation: Efficacy and safety of lifileucel, an autologous tumor-infiltrating lymphocyte cell therapy, and pembrolizumab in patients with immune checkpoint inhibitor-naive unresectable or metastatic melanoma: updated results from IOV-COM-202 Cohort 1A (Abstract 9505)
Session: Melanoma/Skin Cancers
Friday, May 31, 2024, 2:45 p.m. – 5:45 p.m. CDT
Poster: IOV-3001, a modified interleukin-2 fusion protein, for potential use in tumor-infiltrating lymphocyte cell therapy regimens (Abstract 2552)
Session: Developmental Therapeutics-Immunotherapy
Saturday, June 1, 2024, 9:00 a.m. – 12:00 p.m. CDT
Poster: Dynamics of circulating cytokines and chemokines during and after tumor-infiltrating lymphocyte cell therapy with lifileucel in advanced melanoma patients
Session: Melanoma/Skin Cancers (Abstract 9594)
Saturday, June 1, 2024, 1:30 p.m. – 4:30 p.m. CDT
ASCO 2024 Webcast
Iovance executives and key opinion leaders (KOLs) will discuss ASCO (Free ASCO Whitepaper) data highlights and perspectives on the Amtagvi commercial launch during an audio webcast on Friday, May 31, 2024 at 6:15 p.m. CDT (7:15 p.m. EDT). To listen to the live or archived audio webcast, please register at View Source The live and archived webcast can be accessed in the Investors section of the Company’s website, IR.Iovance.com for one year.

On May 23, 2024 Invitae (OTC:NVTAQ), a leading medical genetics company, reported eight studies to be presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held in Chicago from May 31-June 4, 2024 (Press release, Invitae, MAY 23, 2024, View Source [SID1234643605]). The clinical data being presented demonstrate the importance of genetic testing for patients with various different types of cancers, including breast, gastric, prostate and lung, to better inform management and treatment decisions.

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people.

Genetic testing guidelines need to be inclusive of more cancer types, with new data finding gastric, lung and prostate cancer patients with inherited genes linked to increased cancer risk

Gastric cancer is the fourth leading cause of cancer-related deaths worldwide, and the role of pathogenic (disease causing) variants in cancer predisposition genes is not well understood for this disease. One study looked at genetic testing results in 3,706 gastric cancer patients – the largest study of its kind – to better understand the prevalence of disease causing variants in cancer associated genes. The results found the percentage of patients with disease causing variants to be 13.4%, about 1 in 8 patients. This shows the value of genetic testing in all gastric cancer patients, as the prevalence of pathogenic variants is similar to other cancer types for which guidelines recommend universal genetic testing.

"Current guidelines haven’t met the needs for patients across cancer types, gastric cancer included," said Dr. Ophir Gilad, University of Chicago and a co-author of this study. "The prevalence of actionable gene variants found in this study of gastric cancer patients is on par with other cancer types for which guidelines recommend universal genetic testing. We’re increasingly seeing evidence for germline genetic testing to help guide treatment plans and familial testing for various cancer types."

Additionally, in a study of 14,317 patients with lung cancer, 12.6% had pathogenic germline variants — regardless of smoking history. The study results suggest these inherited genes are not only independently associated with lung cancer, but also additive to smoking risk for lung cancer. These data reinforce prior studies supporting consideration of germline genetic testing for all patients with lung cancer, independent of age or reported smoking history.

Genetic testing is similarly underutilized for prostate cancer. In a large study of 15,000 prostate cancer patients that received genetic testing, results showed that of the patients with genetic variants that increase risk of prostate cancer, 3 in 4 patients had no reported family history of prostate cancer and more than 1 in 3 patients had no reported family history of any cancer. The findings underscore the importance of genetic testing for all prostate cancer patients, regardless of age, stage or family history.

Breast cancer data in Rwanda demonstrates need for more genetic testing in underrepresented populations

Despite the observation that cancers are often diagnosed at young ages and take an aggressive course in Sub-Saharan Africa (SSA), genetic data that could inform treatment are limited for this population group.

In a recent study, patients undergoing cancer treatment in hospitals in Rwanda for female breast, male breast and prostate cancer underwent multigene panel testing (Invitae), and the results found a large proportion of the patients had inherited pathogenic variants that could help inform their treatment (18.3% of female breast cancer, 16.7% of male breast cancer, and 4.3% of prostate cancer patients). The findings suggest that genetic testing should be more routinely implemented into cancer care and prevention strategies in this population.

Underrepresented race, ethnicity, and ancestry (REA) groups face these challenges across geographies. In another recent study being presented at ASCO (Free ASCO Whitepaper) that included more than one million people over an eight-year period who underwent genetic testing for hereditary cancer syndromes, it was found that underrepresented REA groups are disproportionately impacted by variants of uncertain significance (VUS) in genetic testing, which are uncertain results that are not clinically actionable. With more representation of these groups in clinical studies, there will be more data that could uncover life-saving discoveries. Clinical evidence was the most significant source of information leading to VUS resolution, underscoring the importance of the clinician-lab partnership and communication.

"Germline genetic testing should be the standard of cancer care across many types of cancers. In underrepresented populations, this is especially crucial as more information needs to be collected to better inform care and improve population health overall," said Dr. Michael Korn, chief medical officer at Invitae. "Each year, ASCO (Free ASCO Whitepaper) presents us with an opportunity to share compelling research to help propel cancer treatment forward, and we’re proud of the clinical insights our tests are able to provide across cancer types."

Study offers reassurance that variants of uncertain significance in genetic testing results among patients with breast cancer do not lead to overuse of treatment or surveillance interventions, such as mastectomies

It’s common for patients with breast cancer undergoing germline genetic testing to have uncertain results, but it’s previously been unclear if these results impact clinical management. However, a recent study being presented at ASCO (Free ASCO Whitepaper) presents new evidence indicating that variants of uncertain significance (VUS) identified through germline genetic testing do not result in guideline-discordant management in real-world settings. Specifically, patients with breast cancer and VUS results demonstrated similar rates of treatment, prevention and surveillance interventions compared to those with negative results. This offers reassurance that VUS results do not lead to overuse of mastectomies or other interventions for patients with breast cancer.

2024 ASCO (Free ASCO Whitepaper) presentations and posters:

Oral presentation/Abstract 10513: Titled: Tracking uncertainty in germline genetic testing for hereditary cancer syndromes: Sources, attributes and resolution of variants of uncertain significance in over 1 million individuals. Presenter: Brian Reys, MS, CGC
Oral presentation/Abstract 10512: Titled: Real-world cancer care utilization among patients with breast cancer with germline variants of uncertain significance. Presenter: Allison W. Kurian, MD, MS, MSc, FASCO
Poster 374/Abstract 6058: Titled: The combination of patient-specific tumor and HPV sequencing to enable high-sensitivity detection of ctDNA in patients with HPV-associated oropharyngeal carcinoma. Presenter: Bill Diplas, MD, PhD
Poster 106/Abstract 10579: Titled: Uptake of risk-reduction, surveillance and therapeutic interventions among breast cancer patients with pathogenic germline variants. Presenter: Allison W. Kurian, MD, MS, MSc, FASCO
Poster 508/Abstract 5102: Titled: Germline gene-specific associations in a large prostate cancer cohort. Presenter: Hiba Khan, MD, MPH
Poster 105/Abstract 10578: Titled: Prevalence of pathogenic genetic variants in patients with gastric cancer ascertained through multi-gene panel testing. Presenter: Ophir Gilad, MD
Poster 118/Abstract 10591: Titled: Germline sequence variation in Rwandan patients with breast and prostate cancer. Presenter: Achille Manirakiza, MD, MMed
Poster 302/Abstract 8040: Titled: Smoking and pathogenic germline variants in patients with lung cancer. Presenter: Ed Esplin, FACMG, FACP, MD, PhD

On May 23, 2024 IN8bio, Inc. (Nasdaq: INAB) a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, reported an upcoming presentation of updated results from its fully enrolled Phase 1 study of INB-200 at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held May 31st – June 4th in Chicago, Illinois (Press release, In8bio, MAY 23, 2024, View Source [SID1234643604]). INB-200 is evaluating autologous Drug Resistant Immunotherapy (DeltEx DRI) or chemotherapy resistant gamma-delta T cells as a potential first-line treatment for patients with newly diagnosed glioblastoma multiforme (GBM).

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"The current standard-of-care for newly diagnosed GBM has not advanced progression-free survival (PFS) beyond 4-7 months or overall survival beyond 14-16 months for over two decades," said William Ho, CEO and co-founder, IN8bio. "We’re excited to update the status of patients who received INB-200 for front-line GBM in addition to standard-of-care at the upcoming ASCO (Free ASCO Whitepaper) Annual Meeting. We believe these findings will continue to validate the potential of DeltEx DRI as a novel therapy for patients with GBM. We are advancing our gamma-delta T cell therapy to help address this significant unmet need and look forward to presenting additional trial results at ASCO (Free ASCO Whitepaper) and throughout the year."

Details of the 2024 ASCO (Free ASCO Whitepaper) poster presentation are provided below:

Poster title: INB-200: Fully enrolled Phase 1 study of gene-modified autologous gamma-delta (γδ) T cells in patients with newly diagnosed glioblastoma multiforme (GBM) receiving maintenance temozolomide (TMZ)
Authors: Mina Lobbous, Trishna Goswami, Lawrence Lamb, Kate Rochlin, Thriumaine Pillay, Mariska ter Haak, Louis Nabors
Date/Time: Saturday, June 1, 2024 from 10:00 a.m. – 1:00 p.m. EDT
Presenter: Dr. Mina Lobbous, University of Alabama at Birmingham
Session Title: Central Nervous System Tumors
Abstract #: 2042
Poster Board: #341

Abstract: The Phase 1 study enrolled 23 patients with newly diagnosed GBM who exhibited adequate organ function and a Karnofsky Performance Status (KPS) of ≥ 70%. Patients were administered 1, 3, or 6 doses of DeltEx DRI, consisting of 1 x 107 DRI cells, into the resection cavity along with 150 mg/m2 of intravenous TMZ on Day 1 and oral TMZ on days 2-5 of each Stupp maintenance cycle.

DeltEx DRI was successfully infused with peripheral TMZ-based lymphodepletion evidenced with near or below normal range T, B, and NK subsets for up to one year. The majority of patients dosed exceeded the expected median PFS of 7 months with Stupp therapy alone, demonstrating a continued encouraging trend in PFS. Long-term follow-up for durability of PFS and OS continue.

The Phase 1 study results reported no dose-limiting toxicities, cytokine release syndrome, or neurotoxicity. The most common adverse events were decreased white blood cell and platelet count, asthenia, fatigue, hydrocephalus, headache, decreased appetite, urinary tract infection, thrombosis, and balance disorder.

Autologous DeltEx DRI is a gene-modified autologous gamma-delta T cell therapy designed for the treatment of newly diagnosed GBM patients receiving maintenance TMZ therapy. Gamma delta T cells can target NKG2D ligands that are upregulated on tumor cells following exposure to alkylating chemotherapy, leveraging the unique capabilities of this investigational therapy to enable concomitant therapy and continued surveillance against tumor cells.

More details of the Phase 1 study can be found at www.clinicaltrials.gov (NCT04165941).

Abstract can be accessed online at View Source beginning at 5:00 p.m. EDT on May 23, 2024.