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Cardiff Oncology Announces Positive Initial Data from First-line RAS-mutated mCRC Clinical Trial

On December 10, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported positive initial data from CRDF-004, a randomized, Phase 2 clinical trial evaluating onvansertib in combination with standard-of-care (SoC) in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, DEC 10, 2024, View Source [SID1234648975]). Efficacy and safety data are for all evaluable patients as of a November 26, 2024 data cut-off date, and all efficacy data are determined by a blinded, independent central review (BICR) of each patient’s tumor scan.

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"We are highly encouraged by the robust efficacy signal and favorable safety profile observed with onvansertib plus standard-of-care from the first 30 evaluable patients in our randomized first-line RAS-mutated mCRC CRDF-004 trial," said Fairooz Kabbinavar, MD, FACP, Chief Medical Officer of Cardiff Oncology. "Our data shows an objective response rate of 64% in patients receiving the 30 mg dose of onvansertib in combination with standard of care, significantly higher than the 33% objective response rate observed in the control arms of standard of care alone. In addition, as can be seen in the spider plots, we are observing deeper tumor response in patients receiving the 30mg dose of onvansertib compared to those receiving the 20mg dose with similar safety profiles for both doses."

Study Design

The CRDF-004 phase 2 trial is currently enrolling patients with mCRC who have a documented KRAS or NRAS mutation. Onvansertib is added to SoC consisting of FOLFIRI plus bevacizumab or FOLFOX plus bevacizumab. Patients are being randomized in a 1:1:1 ratio to either 20mg of onvansertib plus SoC, 30mg of onvansertib plus SoC, or SoC alone. The primary endpoint is objective response rate (ORR), and the secondary endpoints include progression-free survival (PFS), duration of response (DOR) and safety.

Efficacy Data

Objective Response Rates observed in the CRDF-004 clinical trial, as of the data cut-off date of November 26, 2024, are shown below.

Control Arm

(SoC alone)

20mg dose of onvansertib + SoC

30mg dose of onvansertib + SoC

All onvansertib patients

33% ORR

(3 of 9)

50% ORR

(5 of 10)

64% ORR

(7 of 11)

57% ORR

(12 of 21)

Spider Plots, displaying the change in tumor size from baseline for each patient over time, demonstrate deeper responses observed in patients receiving the 30mg dose of onvansertib in combination with the SoC compared to both the control arms and 20mg dose of onvansertib arms.

Safety and Tolerability

Onvansertib in combination with chemo/bevacizumab was well-tolerated and there have been no major or unexpected toxicities observed.

"Overall, these data support our belief that onvansertib has potential to change the treatment paradigm for the entire first-line RAS-mutated mCRC patient population of almost 50,000 new patients diagnosed in the U.S. annually," said Mark Erlander, Chief Executive Officer of Cardiff Oncology. "In addition to the efficacy signal observed, the data demonstrate that onvansertib can safely be combined with the two different chemo backbones that are currently approved as standard of care in the first-line setting, thus providing a key differentiated profile over previous generation PLK1 inhibitors. We look forward to providing additional clinical updates from our CRDF-004 trial in the first half of 2025."

Upcoming expected milestones

•
Additional clinical data from CRDF-004 trial expected in 1H 2025

Conference Call and Webcast

Cardiff Oncology will host a conference call and live webcast at 8:00 a.m. ET / 5:00 a.m. PT on December 10, 2024. Individuals interested in listening to the live conference call may do so by using the webcast link in the "Events" section of the company’s website. A webcast replay will be available in the investor relations section on the company’s website following the completion of the call.

Arvinas and Pfizer Announce Initial Phase 1b Data from the TACTIVE-U Sub-Study of Vepdegestrant in Combination with Abemaciclib at 2024 San Antonio Breast Cancer Symposium

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.

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.

ALX Oncology Announces New Data Demonstrating Evorpacept in Combination with Zanidatamab Generates Promising Antitumor Activity in Advanced Breast Cancer

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).

"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.

Akoya Biosciences and NeraCare Enter into an Exclusive Global License Agreement for the Development and Commercialization of the Immunoprint Test for Early-Stage Melanoma Patient Treatment Decisions

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.

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.

Curis Announces Additional Data from TakeAim Leukemia Study

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]).

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."