On December 10, 2024 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported preliminary data from the ongoing Phase 1b portion of the TACTIVE-U sub-study of vepdegestrant in combination with abemaciclib among patients with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (Press release, Arvinas, DEC 10, 2024, View Source [SID1234648974]). These data will be presented in a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.

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Preliminary results from 16 patients in the Phase 1b sub-study demonstrated a tolerable safety profile for the combination of abemaciclib 150 mg twice daily (BID) with the recommended Phase 3 monotherapy dose of vepdegestrant (200mg once daily; QD). An encouraging clinical benefit rate of 62.5% was observed among patients with both mutant ESR1 and wild-type ESR1 disease who had all been previously treated with a CDK4/6 inhibitor.

Pharmacokinetic data demonstrated no significant drug-drug interaction between vepdegestrant and abemaciclib and no clinically meaningful effect on abemaciclib exposure was observed. In addition to tolerability, the results demonstrated a safety profile consistent with both the known properties of abemaciclib and observed data in other clinical trials for vepdegestrant. These findings support the ongoing Phase 2 portion of the study, which is evaluating full dose abemaciclib (150mg BID) in combination with vepdegestrant (200 mg QD) in post-CDK4/6 advanced breast cancer.

"The preliminary results from this Phase 1b sub-study in patients whose cancer had previously progressed after receiving a CDK4/6 inhibitor are encouraging," said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. "These data further reinforce our belief that vepdegestrant can be used in multiple combination regimens across the metastatic breast cancer setting and has the potential to become a best-in-class backbone ER therapy. We are pleased to continue in the Phase 2 portion of the study evaluating the standard starting dose of abemaciclib in combination with vepdegestrant."

"With vepdegestrant, we aim to develop a novel agent that has the potential to become a new backbone endocrine therapy in ER+ metastatic breast cancer," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer​. "We are pleased to see these initial results, which complement previously reported data demonstrating the potential of combination therapy with vepdegestrant to address unmet needs for patients."

Additional detail on the TACTIVE-U poster presentation at SABCS follows below:

Title: Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, Plus Abemaciclib in ER-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced or Metastatic Breast Cancer: TACTIVE-U Preliminary Phase 1b Results
Date: Thursday, December 12, 2024
Time: 5:30 – 7:00 p.m. CDT
Poster: P4-12-03

Key findings included in the poster (data cut-off: August 30, 2024):

100% of patients had prior treatment with a CDK4/6 inhibitor.
Tolerability is generally consistent with the profile of abemaciclib and with results previously observed in other clinical trials of vepdegestrant. The most common any grade treatment-emergent adverse events (TEAE) were diarrhea, nausea and fatigue. There were no dose-limiting toxicities and no grade 4 or 5 TEAEs.
There was no significant drug-drug interaction, and data reflected vepdegestrant has no clinically meaningful effect on abemaciclib exposure.
Encouraging preliminary antitumor activity is observed with a clinical benefit rate (CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥ 24 weeks) of 62.5% in all CBR-eligible patients (10/16), 62.5% in patients with mutant ESR1 (5/8), and 62.5% in patients with wild-type ESR1 (5/8).
The objective response rate (ORR) in evaluable patients was 26.7% overall (4/15), 37.5% in patients with mutant ESR1 (3/8), and 14% in patients with wild-type ESR1 (1/7).
Five patients remained on study treatment as of the August 30, 2024 data cut-off.
Arvinas and Pfizer are continuing to evaluate data from the ongoing TACTIVE-U clinical trial, which includes combinations of vepdegestrant plus abemaciclib, ribociclib or samuraciclib (ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).

About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.

The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.

On December 10, 2024 ALX Oncology Holdings Inc. ("ALX Oncology" or "the Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives, reported results from a Phase 1b/2 clinical trial demonstrating the company’s investigational CD47-blocker evorpacept in combination with Jazz Pharmaceuticals’ zanidatamab generates promising anti-tumor activity in patients with both HER2-positive and HER2-low advanced breast cancer (Press release, ALX Oncology, DEC 10, 2024, View Source [SID1234648973]). The findings, which are the first from a clinical trial evaluating the safety and efficacy of evorpacept and zanidatamab in heavily pretreated patients with metastatic breast cancer (mBC), will be presented on Thursday, December 12 in a poster spotlight presentation (#PS8-09) at the 2024 San Antonio Breast Cancer Symposium (SABCS).

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"These data suggest that HER2-positive patients whose cancer has been heavily pretreated may benefit from CD47 inhibition via evorpacept’s unique mechanism when combined with a HER2-targeted agent," said Alberto J. Montero, M.D., MBA, Clinical Director, Breast Cancer Medical Oncology Program, Case Western Reserve University, and the study’s principal investigator. "New therapeutic options with better safety profiles are desperately needed for these patients, and this is particularly true once disease progresses following advanced, standard-of-care therapies such as ENHERTU."

The Phase 1b/2 open-label, multi-center clinical trial (NCT05027139) evaluated the potential of evorpacept, a highly differentiated, investigational CD47 blocker, in combination with zanidatamab, a dual HER2-targeted bispecific antibody, as a novel treatment for patients with previously treated inoperable, locally advanced, or metastatic HER2-expressing breast cancer and other cancers.

Part one of the trial evaluated the safety and recommended doses for the combination; part two assessed the anti-tumor activity of the resulting combination. The SABCS poster presentation will include efficacy findings from all three of the part-two trial cohorts: Cohort 1 (n=21) consisted of patients with HER2-positive breast cancer who had received a median of six prior systemic therapies in the metastatic setting. Notably, all patients in Cohort 1 had received prior fam-trastuzumab deruxtecan-nxki (ENHERTU). Patients were enrolled based on local assessment of tumor samples or central assessment. Of the 21 patients enrolled in Cohort 1, nine were found to be HER2-positive based on central assessment. Cohort 2 (n=15) consisted of patients with HER2-low breast cancer who had received a median of five prior systemic therapies. Cohort 3 (n=8) consisted of patients with other HER2-expressing cancers.

Key trial results to be shared at SABCS 2024 include:

HER2-positive by central assessment mBC: Patients in Cohort 1 who were HER2-positive by central assessment (n=9) showed the greatest anti-tumor activity with a confirmed objective response rate (cORR) of 55.6% and a median progression free survival (mPFS) of 7.4 months.
HER2-positive mBC: Overall, patients in Cohort 1 (n=21) had a confirmed cORR and mPFS of 33.3% and 3.6 months, respectively.
HER2-low mBC: Responses were also observed in Cohort 2 (cORR: 20.0%; mPFS: 1.9 months).
As of the August 2024 data cutoff, median follow-up was 9.6 months, with six patients still on treatment. The median duration of response was not reached for Cohort 1 patients (range: 3.6-25.9 months) and was 5.5 months for Cohort 2 patients (range: 3.6-11.0 months), with responses ongoing, including the longest observed response, in each cohort.
Most treatment-related adverse events were grade 1 or 2. The most frequent adverse events due to any cause were fatigue, nausea, diarrhea, and infusion-related reactions. There were no treatment-related deaths in the study and no non-infectious pulmonary toxicities. These safety findings are consistent with those observed in the >700 patients treated with evorpacept to date.

"This study adds to the growing body of evidence suggesting that evorpacept can treat HER2-positive cancers after patients progress on multiple conventional HER2-directed therapies, given that the encouraging response rate of 55 percent in this population would not be expected," said Jason Lettmann, Chief Executive Officer at ALX Oncology. "The data that will be presented this week also further validate our biomarker strategy, showing that confirmed HER2-expression drove the largest benefit for patients. Collectively, these findings provide us with the proof of concept necessary to accelerate our clinical plans to advance evorpacept in HER2-positive breast cancer."

A copy of the poster presentation will be available on the Publications section of ALX Oncology’s website at the start of the presentation at SABCS on December 12, 2024.

On December 10, 2024 Akoya Biosciences, Inc. (Nasdaq: AKYA), The Spatial Biology Company, and NeraCare, a leading developer of laboratory tests for the prognosis of melanoma, reported an exclusive global license agreement to develop and commercialize NeraCare’s Immunoprint test on Akoya’s multiplexed immunofluorescent platform (Press release, Akoya Biosciences, DEC 10, 2024, View Source [SID1234648972]). Building on the research collaboration between the companies announced earlier this year, the license agreement grants Akoya the exclusive right to develop, market and commercialize the test for clinical research, diagnostic development or, following regulatory approval, patient clinical testing as both a laboratory test or a distributable diagnostic on Akoya’s PhenoImager HT platform.

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Melanoma, the leading cause of skin cancer, sees over 235,000 new diagnoses every year, 80% of which are in early-stage disease (IA/IB/IIA). While these early-stage patients undergo surgery and subsequent monitoring, they are ineligible to receive effective adjuvant therapies approved for later stage melanoma. NeraCare’s Immunoprint assay addresses this critical unmet need by identifying early-stage melanoma patients at high risk of relapse, comparable to later-stage patients, making them ideally suited to potentially benefit from therapeutic options.

"The agreement builds on the complementary expertise of both companies: Akoya’s market-leading multiplex immunofluorescence technology and NeraCare’s innovative development and rigorous clinical validation of Immunoprint. Together, we aim to expand access to life-saving therapies for early-stage melanoma patients worldwide," said Friedrich Ackermann, Co-Founder of NeraCare.

"Our collaboration is a testament to the versatility of Akoya’s PhenoImager HT platform and the clinical impact spatial biology can deliver. Immunoprint has proven unparalleled in identifying high-risk melanoma patients through multiple clinical studies, and our partnership aims to offer a platform to address the unmet need for earlier therapeutic intervention," added Daniel von Janowski, Co-Founder of NeraCare.

"Our exclusive partnership with NeraCare for Immunoprint is a significant advancement of our clinical strategy providing Akoya and our pharmaceutical partners the opportunity to transform melanoma patient care We are honored to be partnering with NeraCare to help bring this test to market and serve a critical unmet need," said Brian McKelligon, CEO of Akoya Biosciences.

On December 10, 2024 Curis, Inc. ("Curis") (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib (CA-4948), an orally available, small molecule IRAK4 inhibitor, reported data from the TakeAim Leukemia study (CA-4948-102) in relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) at the 66th ASH (Free ASH Whitepaper) annual meeting (Press release, Curis, DEC 10, 2024, View Source [SID1234648969]).

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The additional data presented include data for 21 patients with a FLT3 mutation (FLT3m) who had received fewer than 3 lines of prior therapy and were treated with emavusertib as monotherapy at the Recommended Phase 2 Dose (RP2D) of 300 mg BID. This brings the total number of patients dosed at the RP2D from 12 to 21 patients.

Data show 10 objective responses in 19 response-evaluable patients: 6 complete remission (CR), 2 CR with either a complete remission with incomplete hematological recovery (CRi) or a partial hematological recovery (CRh) and 2 morphologic leukemia-free state (MLFS). Prior therapies of responders included Venetoclax (5/10), HMA (6/10), and FLT3i (6/10). Two of the 21 patients were treated, but discontinued treatment prior to first disease assessment (death occurred at Day 8 and Day 13, respectively), and were not included as response-evaluable patients.

Two patients who achieved a CR and CRi, respectively, proceeded to allogenic stem cell transplantation. Responses were achieved rapidly in this population, with 7 of 10 responses reported at the first assessment (Cycle 2 Day 1).

"We continue to be pleased with the monotherapy data in R/R AML patients with a FLT3 mutation," said James Dentzer, President and CEO of Curis, "and believe these data further support the exciting potential of emavusertib’s novel mechanism to address a significant unmet need in patients with AML."

On December 9, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with solid tumors or hematologic malignancies, reported initial positive clinical data from the multi-center Phase 1-2 study of IMPT-314 in patients with large B-cell lymphoma that is being presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Lyell Immunopharma, DEC 10, 2024, View Source [SID1234648922]). IMPT-314 is an autologous dual-targeting CD19/CD20 chimeric antigen receptor (CAR) T-cell product candidate being developed for patients with aggressive B-cell non-Hodgkin lymphoma.

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As of October 22, 2024 (the data cutoff for the presentation), 23 patients with relapsed or refractory (R/R), CAR T-naive large B-cell lymphoma received IMPT-314. The efficacy evaluable population consisted of 17 patients. The ORR was 94% (16/17 patients), with 71% (12/17 patients) achieving a CR by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were in response at last follow-up). In the safety evaluable population of 23 patients, no Grade 3+ CRS was reported. Grade 3 ICANS was reported in 13% (3/23) of patients with a median time to complete ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy. In the efficacy evaluable set, 16 patients were evaluable for pharmacokinetics. IMPT-314 demonstrated robust expansion and peak cell expansion occurred between Days 7 – 28 post IMPT-314 infusion (median Tmax = 10 days). Additionally, the final drug product contained the desired naïve and central memory cell phenotype (median, 91%; range, 82 – 99%) that has been associated with improved overall survival in other CAR T cell clinical studies.

The data are being presented today at the 2024 ASH (Free ASH Whitepaper) Annual Meeting by Sarah M. Larson, M.D., Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, and the poster is available in the Investors’ section of the Company’s website.

"The high rate of complete responses with a favorable safety profile support the strong potential of IMPT-314, Lyell’s next-generation dual-targeting CAR T-cell therapy enriched for naïve and central memory T cells. This product candidate was designed to maximize durable responses by overcoming heterogeneous CD19 antigen density and antigen escape, enhance CAR T cell persistence, and reduce exhaustion," said Lynn Seely, M.D., Lyell’s President and Chief Executive Officer. "Based on these strong data, we remain on track to initiate a pivotal trial in 2025 of IMPT-314 in CAR T-naive patients with large B-cell lymphoma in the 3rd-line+ setting and are continuing to evaluate IMPT-314 in the 2nd-line setting in the ongoing Phase 1-2 trial."

"The data presented today from IMPT-314 suggest the potent targeting of both CD19 and CD20 coupled with CD62L+ cell enrichment has the potential to provide differentiated benefit in objective and complete response rates over first-generation CD19 CAR therapies in patients with aggressive large B-cell lymphoma," stated Sarah M. Larson, M.D., Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA. "IMPT-314 incorporates the same CAR construct as CART19/20 which was evaluated in a Phase 1 trial at UCLA, and I am pleased that the IMPT-314 data are consistent with our experience at UCLA."

About IMPT-314

IMPT-314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the response as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.

IMPT-314 is designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both. IMPT-314 is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity.

IMPT-314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory aggressive B-cell lymphoma.