On November 25, 2024 Rznomics, Inc. reported to secure its expanded access program (EAP) from the United States Food and Drug Administration (FDA) for RZ-001, RNA editing gene therapy product for the treatment of patients aged 18 and older with Glioblastoma (GBM) (Press release, Rznomics, NOV 25, 2024, View Source [SID1234648631]).

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Generally, the EAP also known as ‘compassionate use,’ is a pathway provided by the U.S. FDA that allows patients with serious or immediately life-threatening conditions to gain access to investigational medical products (drugs, biologics, or medical devices) outside of clinical trials.

GBM is known as the most malignant tumor in Central Nervous system with high mortality rate but lacks effective therapies. TERT promoter mutations, which are associated with TERT upregulation, are found in up to 80% of glioblastoma (GBM) patients. This increased TERT expression is strongly linked to a poor prognosis, reflecting the aggressive nature of the disease. RZ-001, the RNA replacement enzyme-based cancer gene therapy, targets and cleaves hTERT mRNA and replaces the mRNA with the therapeutic gene RNA. This induces anti-cancer activity and cytotoxic effect by reducing hTERT expression and simultaneously trans-ligating an HSVtk-encoding sequence into the reprogrammed hTERT mRNA.

"We are excited to offer RZ-001 through this EAP, providing a potential new treatment option for GBM patients with limited alternatives," said Dr. Chiocca, Professor at Harvard Medical School executive Director of the Center for Tumors of the Nervous System at Mass General Brigham Cancer Institute.

Seong-Wook Lee, PhD, CEO of Rznomics, stated, "We hope RZ-001 can serve as a good alternative for patients who have had difficulty with existing treatments." He also assured that the Rznomics team is committed to expediting the clinical development process to secure timely market authorization.

In previous releases, Rznomics noted that RZ-001 has received Fast Track designations and Phase I/IIa IND approval for RZ-001 from the FDA and the South Korean Ministry of Food and Drug Safety (MFDS) in Glioblastoma and the clinical trial has been investigating the safety, tolerability, and efficacy of RZ-001 in patients with GBM. A clinical trial has recently commenced, marking the start of RZ-001 administration.

On November 25, 2024 Arvinas, Inc. (Nasdaq: ARVN) reported that three posters for vepdegestrant, including clinical data, will be presented at the 2024 San Antonio Breast Cancer Symposium (SABCS), being held December 10-13, 2024, in San Antonio, Texas (Press release, Arvinas, NOV 25, 2024, View Source [SID1234648600]). Vepdegestrant is a novel investigational PROTAC estrogen receptor (ER) degrader that is being jointly developed by Arvinas and Pfizer for the treatment of patients with early and locally advanced or metastatic estrogen receptor positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.

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Poster session details are as follows:

Poster Title: Evaluation of the Combination of Vepdegestrant, a PROTAC Estrogen Receptor (ER) Degrader, Plus Palbociclib in CDK4/6 Inhibitor-Resistant WT ER and ER Y537S Mutant Patient Derived Xenograft (PDX) Models
Poster Session 3 (ID: P3-01-16)
Date: Thursday, December 12
Time: 12:30 p.m. – 2:00 p.m. CT

Poster Title: Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, Plus Abemaciclib in ER-Pos/Human Epidermal Growth Factor Receptor 2 (HER2) Negative Advanced or Metastatic Breast Cancer: TACTIVE-U Prelim Phase 1b Results
Poster Session 4 (ID: P4-12-03)
Date: Thursday, December 12
Time: 5:30 p.m. – 7:00 p.m. CT

Poster Title: Evaluating CYP3A4-Mediated Drug Interaction Risks for Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, in Combination with Cyclin Dependent Kinase (CDK)4/6 Inhibitors and Everolimus
Poster Session 4 (ID: P4-08-13)
Date: Thursday, December 12
Time: 5:30 p.m. – 7:00 p.m. CT

For copies of the abstracts, please visit the official SABCS website here.

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 (HER2) negative (ER+/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 November 25, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that management will participate in the following investor conferences in December (Press release, ORIC Pharmaceuticals, NOV 25, 2024, View Source [SID1234648616]):

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7th Annual Evercore HEALTHCONx Conference – Participating in a fireside chat on Wednesday, December 4, 2024, at 2:35 p.m. ET

Citi’s 2024 Global Healthcare Conference – Participating in the "Novel Mechanisms in Oncology II" panel on Thursday, December 5, 2024, at 11:00 a.m. ET

Live webcasts of the discussions will be available through the investor section of the company’s website at www.oricpharma.com. Replays of the webcasts will be available for 90 days following the events.

On November 25, 2024 Agendia, Inc., reported that new data on its early-stage breast cancer genomic tests and their ability to inform treatment selection decisions will be presented at the San Antonio Breast Cancer Symposium 2024 (SABCS), taking place in San Antonio, TX, December 10th – 13th, 2024 (Press release, Agendia, NOV 25, 2024, View Source [SID1234648633]).

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The presented data highlights Agendia’s continued focus on expanding clinical utility of the tests and optimizing breast cancer management throughout the patient’s treatment journey. These studies further enhance the robust body of clinical research supporting the clinical utility of Agendia’s MammaPrint and BluePrint in providing reliable guidance for therapeutic decisions in early-stage breast cancer.

Five Agendia abstracts have been accepted, including two poster spotlight presentations and one late-breaking poster. The following are details of the abstracts that have been accepted, which can also be found on the SABCS website here:

Poster Spotlight Presentations:

MammaPrint and BluePrint Predict Pathological Response to Neoadjuvant Chemotherapy in Patients with HR+HER2- Early-Stage Breast Cancer Enrolled in FLEX.
Authors: O’Shaughnessy, J., et al.
Session: Poster Spotlight Session 4: Prediction of Chemotherapy Response
Date/Time: Wednesday, December 11 | 7:00 AM – 8:30 AM CST
Abstract #: 2091
Association of MammaPrint with Gene Expression Pathways Predictive of Resistance to Cyclin Dependent Kinase Inhibition
Authors: Brufsky, A., et al.
Session: Poster Spotlight Session 2: Personalizing CDK 4/6 Inhibitor Therapy for Patients with Metastatic Breast Cancer: Survival, QOL and Biomarkers
Date/Time: Thursday, December 12 | 7:00 AM – 8:30 AM CST
Abstract #: SESS-2068
Poster Presentations:

Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine – Biology is Still King
Authors: Rahman, R., et al.
Session: Poster Session 1
Date/Time: Wednesday, December 11 | 12:30 PM – 2 PM CST
Abstract #: 1879
FLEX: A Real-World Evidence, Full Transcriptome Study in 30,000 Patients with Early-Stage Breast Cancer
Authors: Maganini, R.
Session: Poster Session 2
Date/Time: Wednesday, December 11 | 5:30 PM – 7:00 PM CST
Abstract #: 2160
Late-Breaking Poster:

Prediction of Chemotherapy Benefit by MammaPrint in HR+HER2- Early-Stage Breast Cancer Revealed by the FLEX Registry of Real-World Data
Authors: Brufsky, A., et al.
Session: Poster Session 2
Date/Time: Wednesday, December 11 | 5:30 PM – 7:00 PM CST
Abstract #: 3660
In addition, William Audeh, MD, MS, Chief Medical Officer of Agendia, will be presenting at Agendia’s Product Theater session, titled "How Can Genomic Information From A Single Core Biopsy Sample Inform Multiple Therapy Decisions For Early-Stage ER+ Breast Cancer?," demonstrating how MammaPrint and BluePrint can inform early-stage ER+ breast cancer treatment decisions. The educational session will take place on December 11th at 5:30 PM – 6:30 PM CST. Registration details can be found here.

More information about the full program can be found at the SABCS 2024 website.

On November 25, 2024 Astrazeneca reported that positive high-level results from the CAPItello-281 Phase III trial showed Truqap (capivasertib) in combination with abiraterone and androgen deprivation therapy (ADT) demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of radiographic progression-free survival (rPFS) versus abiraterone and ADT with placebo in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC) (Press release, AstraZeneca, NOV 25, 2024, View Source [SID1234648601]).

Overall survival (OS) data were immature at the time of this analysis; however, the Truqap combination showed an early trend towards an OS improvement versus abiraterone and ADT with placebo. The trial will continue as planned to further assess OS as a key secondary endpoint.

Prostate cancer is the second most prevalent cancer in men and the fifth leading cause of male cancer death globally.1 Only one third of patients with metastatic prostate cancer survive five years after diagnosis.2 Newly diagnosed mHSPC is an aggressive form of the disease associated with poor outcomes and survival.3,4 Approximately 200,000 patients are diagnosed with mHSPC each year, and one in four have PTEN-deficient tumours.5 Patients with a tumour biomarker of PTEN deficiency have a particularly poor prognosis.6

Karim Fizazi, MD, PhD, Institut Gustave Roussy, and University of Paris Saclay in Villejuif, France, and principal investigator for the trial said: "Patients with this aggressive form of prostate cancer with tumour PTEN deficiency currently face a particularly poor prognosis, and there is an urgent need for new treatments that improve upon current therapies. The results seen with capivasertib in combination with abiraterone-prednisone and androgen deprivation therapy in the CAPItello-281 trial represent a step forward for these patients."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "These results show for the first time, that adding an AKT inhibitor to a standard-of-care therapy can provide benefit to patients with a biomarker of PTEN-deficient metastatic hormone-sensitive prostate cancer. By targeting a key driver of the disease, we have been able to improve upon current therapies and demonstrate the potential role of this combination in an area of critical unmet need. It will be important to see greater maturity in key secondary endpoints including overall survival."

The safety profile of Truqap in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each medicine.

Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

Notes

Prostate cancer
Prostate cancer is the second most prevalent cancer in men and the fifth leading cause of male cancer death globally, with an incidence of more than 1.4 million and approximately 397,000 deaths in 2022.1

Metastatic prostate cancer is associated with a significant mortality rate, with only one third of patients surviving five years after diagnosis.2 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.7

Metastatic hormone-sensitive prostate cancer
In patients with mHSPC, also known as metastatic castration-sensitive prostate cancer (mCSPC), prostate cancer cells need high levels of androgens to drive cancer growth.4,7 Hormone therapies, such as ADT, are widely used to block the action of male sex hormones and lower the levels of androgens in the body.4,8 However, resistance to these therapies is common and there is a need to extend their use to delay disease progression and castration resistance, where the prostate cancer grows and spreads to other parts of the body despite the use of these therapies.3,4,8

In patients with de novo mHSPC, the cancer has spread to distant parts of the body at the time of first diagnosis.9

PTEN-loss or deficiency fuels the growth of cancer cells, leading to dysregulation of the PI3K/AKT pathway, and is associated with poor outcomes in patients with prostate cancer.6,10

CAPItello-281
CAPItello-281 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of Truqap in combination with abiraterone and ADT versus abiraterone and ADT in combination with placebo in the treatment of patients with PTEN-deficient de novo mHSPC.

The global trial enrolled 1,012 adult patients with histologically confirmed de novo hormone-sensitive prostate adenocarcinoma and PTEN deficiency as confirmed by central testing. The primary endpoint of the CAPItello-281 trial is rPFS as assessed by investigator, with OS as a secondary endpoint.

Truqap
Truqap is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). Truqap 400mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition.

Truqap is approved in the US, EU, Japan and several other countries for the treatment of adult patients with HR-positive (or ER-positive), HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN) following recurrence or progression on or after an endocrine-based regimen based on the results from the CAPItello-291 trial. Truqap is also approved in Australia for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine based regimen based on these trial results.

Truqap is currently being evaluated in Phase III trials for the treatment of breast cancer (CAPItello-292) and prostate cancer (CAPItello-280 and CAPItello-281) in combination with established treatments.

Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

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