On May 23, 2024 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported the publication of the abstract for an oral presentation of preliminary clinical results from its investigator-sponsored Phase 2 trial of darovasertib, a first-in-class oral, small molecular inhibitor of protein kinase C (PKC), as neoadjuvant/adjuvant treatment in uveal melanoma (UM) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ideaya Biosciences, MAY 23, 2024, View Source [SID1234643631]).

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Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent’s Hospital in Sydney, who is the leading principal investigator of the Phase 2 study, will present the clinical data from the Phase 2 Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma" (NADOM) study. Details of the presentation are as follows:

Session: Melanoma / Skin Cancers
Title: A Phase 2 Safety and Efficacy Study of Neoadjuvant/Adjuvant Darovasertib for Localized Ocular Melanoma
Date: Monday, June 3, 2024, at 9:51 AM CDT
In summary, 15 patients planned for enucleation with localized UM were treated with darovasertib 300mg twice daily. An initial safety cohort of 3 patients were treated for one month, and the remaining 12 patients were treated in an expansion cohort for up to six months as neoadjuvant treatment prior to their primary intervention (enucleation, plaque brachytherapy or external beam radiotherapy (EBRT)) across three Australian centers.

As of the database lock, 11 patients had completed primary treatment, four remained on neoadjuvant treatment, and six patients received adjuvant darovasertib after primary treatment of their UM with three patients completing the planned six months. At that time, approximately 67% (6 of 9 patients) had confirmed Eye Saved (i.e., converted to plaque brachytherapy or EBRT). Median tumor shrinkage (maximum volume change) was approximately 45% after six months.

The darovasertib monotherapy neoadjuvant treatment was generally well tolerated. Drug-related adverse events (AEs) were predominantly Grade 1 or Grade 2. Thirteen percent of patients reported at least one drug-related Grade 3 adverse event and no drug-related serious adverse events were observed.

Additional patients and further follow up from the abstract summary cut-off date will be presented on the June 3, 2024, ASCO (Free ASCO Whitepaper) oral presentation. A copy of the ASCO (Free ASCO Whitepaper) oral presentation will be available at approximately 10:00am CDT at its Investor Relations portal under "Events" (View Source) on the day of the presentation.

On May 23, 2024 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported that the Company will host a webcast on June 3, 2024 at 6:00 PM CT/7:00 PM ET following the late-breaking oral presentation of results from the pivotal study of PRGN-2012 for the treatment of recurrent respiratory papillomatosis (RRP) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Precigen, MAY 23, 2024, View Source [SID1234643630]). The webcast will include an in-depth review of the PRGN-2012 pivotal data and business update.

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Phase 2 study results will be presented on June 3rd at 8:30 AM CT during ASCO (Free ASCO Whitepaper) in a presentation titled, "PRGN-2012, a novel gorilla adenovirus-based immunotherapy, provides the first treatment that leads to complete and durable responses in recurrent respiratory papillomatosis patients" by Scott M. Norberg, DO, Associate Research Physician, Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute and a lead investigator for the PRGN-2012 Phase 2 clinical study.

Participants may register and access the webcast through Precigen’s website in the Events & Presentations section. An archived recording will be posted to the website following the event.

On May 23, 2024 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a clinical stage biotechnology company whose proprietary INTASYL siRNA gene silencing technology is designed to make immune cells more effective in killing tumor cells, reported it is presenting data about its lead product candidate, PH-762, an INTASYL compound, at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) to be held in Chicago, Illinois (Press release, Phio Pharmaceuticals, MAY 23, 2024, View Source [SID1234643629]).

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Phio is reporting on the completion of the first dose cohort for its on-going open-label Phase 1b clinical study (NCT 06014086) which is designed to evaluate the safety and tolerability of neoadjuvant use of intratumoral PH-762 in cutaneous squamous cell carcinoma (cSCC), melanoma and Merkel cell carcinoma. Stages 1 and 2 cSCC represent 77% of all new cSCC annually. There are no drug products approved for treatment of Stages 1 and 2 cSCC.

"We are pleased to share our progress in this trial with the oncology community," said Mary Spellman MD, Phio’s acting Chief Medical Officer. "We believe that this immuno-oncology therapy may offer patients meaningful clinical benefit, while minimizing surgical interventions."

Presentation Details:

Title: INTASYL PH-762: PD-1 Intratumoral Immunotherapy for Cutaneous Carcinoma

Poster Number: TPS9620
Topic: Melanoma/Skin Cancer
Presenting Author: Mary Spellman, M.D.
Date and Time: June 1, 2024: 1:30-4:30 PM CDT

On May 23, 2024 Blueprint Medicines Corporation (Nasdaq: BPMC) reported updated data from the ongoing Phase 1 dose escalation portion of the VELA clinical trial of BLU-222, an investigational, highly selective and potent CDK2 inhibitor, in combination with ribociclib and fulvestrant in patients with hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (Press release, Blueprint Medicines, MAY 23, 2024, View Source [SID1234643628]). The data, which mark the first promising clinical results for a CDK2 inhibitor in combination with an approved CDK4/6 inhibitor, will be presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2, 2024.

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"At ASCO (Free ASCO Whitepaper), we will present highly encouraging clinical data showing that our selective CDK2 inhibitor BLU-222, in combination with ribociclib, a standard of care CDK4/6 inhibitor for HR+ breast cancer, is very well-tolerated and delivers early evidence of clinical activity. This represents a highly significant milestone and holds promise as an important new cornerstone for the treatment of breast cancer, including in the front-line metastatic setting," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "These data validate the potency and selectivity of BLU-222, its potential as a first- and best-in-class CDK2 inhibitor, and its use as the combination partner of choice in breast cancer. With these data in hand, we are advancing ongoing partnering discussions that aim to accelerate development of BLU-222 into registration-directed clinical trials."

Updated Phase 1/2 VELA Trial Results

Based on previously reported positive BLU-222 monotherapy clinical data, a combination dose escalation arm was initiated in the VELA trial to assess the safety and clinical activity of BLU-222 in combination with ribociclib, a CDK4/6 inhibitor approved by the U.S. Food and Drug Administration for advanced or metastatic HR+/HER2- breast cancer, and fulvestrant, a commonly used estrogen receptor antagonist. As of the data cutoff date, 19 patients with HR+/HER2- breast cancer who had progressed on prior CDK4/6 inhibitors were treated with 100 mg to 400 mg twice daily (BID) of BLU-222 plus 400 mg once daily (QD) of ribociclib and combined with fulvestrant.

The combination of BLU-222, ribociclib, and fulvestrant was well-tolerated at all BLU-222 dose levels tested. No dose-limiting toxicities, treatment-related severe adverse events (SAEs), or BLU-222-related treatment discontinuations were reported. Treatment-related hematologic and gastrointestinal AEs were generally mild. The maximum tolerated combination dose has not been identified, and combination dose escalation is ongoing.

Pharmacokinetic data showed dose-proportional exposures of BLU-222, with sustained coverage above the predicted efficacious concentration at the 400 mg BID dose level. In addition, the combination of BLU-222 with ribociclib and fulvestrant had no clinically meaningful impact on individual drug exposures.

Preliminary clinical activity showed compelling reductions in thymidine kinase 1 (TK1) and circulating tumor DNA (ctDNA), biomarkers that have been shown to be predictive of clinical benefit. TK1, a biomarker of tumor proliferation, had the deepest reduction among patients treated with BLU-222 400 mg BID, ribociclib 400 mg QD, and combined with fulvestrant, and was statistically significantly correlated with BLU-222 exposure. All patients with evaluable ctDNA, a biomarker of tumor burden, treated with the BLU-222 400 mg BID combination dose regimen showed ctDNA reductions. Early evidence of clinical benefit includes an unconfirmed partial response in a patient who had previously progressed following six lines of therapy in the metastatic setting, including prior palbociclib and trastuzumab deruxtecan. These data highlight the impact of CDK2 inhibition when BLU-222 is combined with other therapies.

Detailed data will be presented by Dr. Dejan Duric from the Henri and Belinda Termeer Center for Targeted Therapies at Massachusetts General Hospital on June 2, 2024, during the "Breast Cancer – Metastatic" poster session at 9:00 a.m. CT. At the time of presentation, a copy of the poster will be available in the "Science—Publications and Presentations" section of the company’s website at www.BlueprintMedicines.com.

About BLU-222

BLU-222 is a highly selective and potent investigational CDK2 inhibitor with first- and best-in-class potential, designed by scientists at Blueprint Medicines. CDK2 is a cell cycle regulator and an important cancer target, with relevance in HR+/HER2- breast cancer and other malignancies, such as subsets of ovarian and endometrial cancer. Across multiple cancer types, aberrant CCNE1 hyperactivates CDK2, resulting in cell cycle dysregulation and tumor proliferation. Aberrant CCNE1 has been observed as a primary driver of disease, as well as a mechanism of resistance to CDK4/6 inhibitors. In HR+/HER2- breast cancer, the advent of CDK4/6 inhibitors has improved treatment; however, disease progression is nearly universal, and new innovation is needed to improve outcomes and prolong clinical benefit. Historically, CDK2 inhibitor development by others has been challenged due to poor selectivity limiting tolerability and combination potential. Beyond BLU-222, Blueprint Medicines is advancing additional preclinical therapeutic candidates for cell cycle targets including BLU-956, a next-generation CDK2 inhibitor, a CDK2 targeted protein degradation program, and an additional undisclosed research program.

On May 23, 2024 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, reported a novel analysis from the Phase 1b trial of botensilimab in combination with balstilimab (BOT/BAL) in relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC) with no active liver metastases (NLM) will be presented at the upcoming 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 1, 2024 (Press release, Agenus, MAY 23, 2024, View Source [SID1234643627]). The analysis shows that BOT/BAL is active in metastatic sites beyond the lungs and lymph nodes, including the peritoneum, soft tissue, and brain, which have historically been unresponsive to treatment.

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"The findings observed in this analysis are notable in that they are seen within challenging and historically unresponsive metastatic sites of disease," said Dr. Steven O’Day, Chief Medical Officer at Agenus. "Seeing broad activity beyond the lungs and lymph nodes is rare for immunotherapy in MSS mCRC, making BOT/BAL stand out from other treatments. We are committed to advancing BOT/BAL for those living with cancer, with the intent to provide durable long-term benefits."

Patient Demographics

A total of 77 patients with NLM MSS mCRC were treated with 1 or 2 mg/kg BOT every 6 weeks plus 3 mg/kg BAL every 2 weeks.
Patients were heavily pre-treated, with a median of four prior lines of therapy, including 21% who received prior PD-(L)1/CTLA-4 therapy.
Location of NLM sites: 62 patients (81%) had lung involvement, 33 patients (43%) had peritoneal involvement, 32 (42%) patients had lymph node involvement, 15 patients (19%) had soft tissue involvement, and 18 patients (23%) had other sites including the bone and brain.
Clinical Findings

Across different NLM sites, overall response rates (ORR) ranged from 18-33% and disease control rates (DCR) ranged from 67-82%. Overall survival (OS) remained consistent and ranged from 20.7 months to not reached (NR).
No new safety signals were observed.
Presentation Details:

Abstract Title: Botensilimab plus balstilimab in microsatellite stable metastatic colorectal cancer: Assessing efficacy in non-liver metastatic sites.

Abstract Number: 3556

Presenting Author: Marwan Fakih, MD, Division Head, GI Medical Oncology, City of Hope Comprehensive Cancer Center

Session: Poster Session – Gastrointestinal Cancer – Colorectal and Anal

Session Date and Time: June 1, 2024, at 1:30 p.m. – 4:30 p.m. CT

About Botensilimab

Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 900 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.