On January 25, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported the publication of two new studies in Nature Medicine evaluating Natera’s personalized and tumor-informed molecular residual disease (MRD) test, Signatera (Press release, Natera, JAN 25, 2024, View Source [SID1234639490]).

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The first study shows results from the single-arm, phase I AMPLIFY-201 trial evaluating the ELI-002 cancer vaccine. The study enrolled a total of 25 patients (20 pancreatic, 5 colorectal), 21 of whom were Signatera-positive after locoregional treatment. Signatera dynamics were also used as a secondary endpoint to assess tumor biomarker response, together with serum tumor antigens. This study is the first of its kind to have utilized circulating tumor DNA (ctDNA)-positivity in conjunction with other tumor biomarkers for enrollment, highlighting the use of Signatera for detecting early evidence of anti-tumor activity of a drug candidate to help assess for a dose response.

The study reported that tumor biomarker responses were observed in 21/25 patients (84%), and ctDNA clearance was observed in 6/25 patients (24%). In contrast, serum tumor antigens declined but did not clear, highlighting the potential utility of ctDNA to be used as a reliable surrogate biomarker for treatment efficacy.

"We are excited about our partnership with Natera, which has resulted in a successful prospective, phase I clinical trial focused on trial enrichment by enrolling Signatera-positive patients and monitoring therapy response in patients receiving a cancer vaccine," said Christopher Haqq, MD, PhD, Elicio Therapeutic, Inc’s executive vice president, head of research and development, and chief medical officer. "We are optimistic about the potential for this study to improve outcomes for patients with pancreatic and colorectal cancer, who face clinical challenges and are often incurable when ctDNA is detected after treatment."

A second study published in Nature Medicine, called PANDA, is a single-arm, open-label, phase II study that investigated preoperative atezolizumab plus chemotherapy in patients with resectable, non-metastatic gastric and gastroesophageal junction adenocarcinoma. The study included 20 patients who underwent surgery and were evaluated for safety, pathologic response, and survival endpoints, and Signatera was used to detect and monitor ctDNA dynamics in all 20 patients.

The PANDA study found that ctDNA clearance after neoadjuvant therapy correlated with pathologic response in 11/11 patients, while 3/6 patients with poor pathologic response remained ctDNA-positive (P=0.029). None of the patients with complete pathologic response (pCR) were ctDNA-positive, and among the nonresponders who were ctDNA negative (n=3), the study reported superior long-term outcomes. Additionally, ctDNA-positivity at the MRD and follow-up time points was associated with a recurrence rate of 100%.

"We’re pleased to see these excellent results from the PANDA study which demonstrate the strong correlation between ctDNA and pathologic response pre-surgery and the therewith associated recurrence risk, highlighting the potential utility of Signatera in gastric and gastroesophageal cancers," said Myriam Chalabi MD, PhD, medical oncologist, Netherlands Cancer Institute, and principal investigator of the PANDA study.

"PANDA and AMPLIFY-201 add to the growing number of studies supporting the use of Signatera across various GI indications, showing the promise of tumor-informed ctDNA testing to help personalize treatment strategies," said Alexey Aleshin, general manager of oncology and early cancer detection at Natera. "These studies also point to the valuable insights longitudinal ctDNA monitoring can provide in the evaluation of novel therapies."

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard-of-care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

On January 25, 2024 Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative positron emission tomography (PET) radiopharmaceuticals, reported results from a sub-analysis of data from the Phase 3 SPOTLIGHT trial (NCT04186845) which investigated the use of POSLUMA (flotufolastat F 18) PET in suspected biochemical recurrence of prostate cancer (Press release, Blue Earth Diagnostics, JAN 25, 2024, View Source [SID1234639489]). The sub-analysis assessed the impact of POSLUMA on treatment plans for patients with recurrent prostate cancer after curative-intent primary therapy. POSLUMA (flotufolastat F 18) injection (formerly referred to as 18F-rhPSMA-7.3) is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.

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Results highlights:

Flotufolastat F 18 PET imaging was positive for recurrent prostate cancer in 84% (81/97) of patients in the sub-analysis.
In 89% (86/97) of patients, management plans were changed following review of the flotufolastat F 18 PET scan results.
91% (78/86) of changes were considered major, defined as a change in the treatment modality.
75% (6/8) of patients whose plans were changed in favor of watchful waiting had a negative flotufolastat F 18 scan.
All patients with management plans that were revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic flotufolastat F 18-avid lesions.
"Recurrent prostate cancer presents challenges, and the ability to determine the extent and location of recurrent disease to inform appropriate clinical management is key for physicians and their patients, as up to 40% of patients who undergo radical prostatectomy, and up to 50% of patients who undergo radiation therapy will develop local or distant recurrences within 10 years," said Przemyslaw Twardowski, MD, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, Calif., on behalf of the SPOTLIGHT Study Group. "The SPOTLIGHT study investigated the diagnostic performance of POSLUMA PET imaging as a potential decision-making aid in assessing suspected biochemical recurrence of the disease. This sub-analysis further examined the impact of POSLUMA PET imaging on patients’ management plans. Results showed that POSLUMA identified recurrence sites in the majority of patients, frequently resulting in major changes to previously planned management plans. Patient treatment based on visualization of POSLUMA-avid lesions has the potential to facilitate optimal targeting of recurrence sites and help patients avoid futile salvage therapy."

"We are very pleased to present these results to the oncology community at ASCO (Free ASCO Whitepaper) GU," said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Diagnostics. "POSLUMA represents a new class of high-affinity PSMA-targeted radiopharmaceuticals based on novel radiohybrid technology, and provides physicians with clinically useful information based on its performance at low PSA levels, PSMA binding and low urinary bladder activity. Our product has been added to nationally recognized clinical oncology guidelines for prostate cancer, alongside and for all the same categories as the other currently FDA-approved PSMA PET radiopharmaceuticals. POSLUMA is labeled with the radioisotope fluorine-18 (18F) to leverage high image quality and to enable broad, readily available geographic access for patients via the manufacturing and distribution network of our commercial U.S. manufacturer and distributor, PETNET Solutions Inc, A Siemens Healthineers Company."

The findings were discussed in a moderated poster presentation at the ASCO (Free ASCO Whitepaper) GU 2024 Genitourinary Cancers Symposium (ASCO GU) on January 25, 2024. "Impact of 18F-flotufolastat PET on management of patients with recurrent prostate cancer: Data from the SPOTLIGHT study," was presented by Przemyslaw Twardowski, MD, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, Calif., on behalf of the SPOTLIGHT Study Group. Full session details are available in the ASCO (Free ASCO Whitepaper) GU online program here.

About the study

The sub-analysis of SPOTLIGHT data from the 389 patient study assessed the impact of flotufolastat F 18 on planned treatment after curative-intent primary therapy. The present analysis focused on patients who had a flotufolastat F 18 scan and sufficient data for management plan evaluation. Onsite investigators recorded patients’ management plans before and after flotufolastat F 18 PET. Plans were then categorized as "no change," "major change,"" other change," "additional information required" or "intended plan not valid." A "major change" was defined as a change in treatment modality (e.g., salvage radiation to systemic therapy), while "other change" represented a change within a modality (e.g., modified radiation therapy field). All imaging data were then submitted for blinded image evaluation by 3 central readers.

In total, 97 patients (median [range] PSA: 0.08 [0.09-134.6]] ng/mL) had an evaluable flotufolastat F 18 PET scan and sufficient data to evaluate management plan changes. Most patients, 86/97 (89%) had a change to their management plan post-scan. A "major change" was noted for 78 (80%) patients, while 8 (8.2%) had an "other change." Onsite imaging reads showed that both positive and negative flotufolastat F 18 scans influenced management planning. While 88% of revisions occurred after a positive scan, 75% of those whose management plans were revised to watchful waiting had negative scans. All patients with management plans revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic flotufolastat F 18-avid lesions.
No serious adverse reactions were attributed to flotufolastat F 18 in the SPOTLIGHT study. Overall, 16/389 (4.1%) patients had at least one treatment-emergent adverse event that was considered possibly related/related to flotufolastat F 18. The most frequently reported events were: hypertension: 1.8% (n=7); diarrhea: 1.0% (n=4); injection site reaction: 0.5% (n=2), and headache: 0.5% (n=2).
About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) compounds consist of a radiohybrid ("rh") Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells, and they may be radiolabeled with imaging isotopes for PET imaging, or with therapeutic isotopes for therapeutic use – providing the potential for creating a true theranostic technology. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Diagnostics received U.S. Food and Drug Administration approval for its radiohybrid PET diagnostic imaging product for use in prostate cancer in 2023. rhPSMA compounds for potential therapeutic use are investigational and have not received regulatory approval.

Indication and Important Safety Information About POSLUMA

INDICATION

POSLUMA (flotufolastat F 18) injection is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer

with suspected metastasis who are candidates for initial definitive therapy
with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level
IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with POSLUMA PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of POSLUMA for imaging metastatic pelvic lymph nodes in patients prior to initial definitive therapy seems to be affected by serum PSA levels and risk grouping. The performance of POSLUMA for imaging patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. Flotufolastat F 18 uptake is not specific for prostate cancer and may occur in other types of cancer, in non-malignant processes, and in normal tissues. Clinical correlation, which may include histopathological evaluation, is recommended.
Risk of Image Misinterpretation in Patients with Suspected Prostate Cancer Recurrence: The interpretation of POSLUMA PET may differ depending on imaging readers, particularly in the prostate/prostate bed region. Because of the associated risk of false positive interpretation, consider multidisciplinary consultation and histopathological confirmation when clinical decision-making hinges on flotufolastat F 18 uptake only in the prostate/prostate bed region or only on uptake interpreted as borderline.
POSLUMA use contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Advise patients to hydrate before and after administration and to void frequently after administration. Ensure safe handling to minimize radiation exposure to the patient and health care providers.
The adverse reactions reported in ≥0.4% of patients in clinical studies were diarrhea, blood pressure increase and injection site pain.
Drug Interactions: androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F 18 in prostate cancer. The effect of these therapies on performance of POSLUMA PET has not been established.
To report suspected adverse reactions to POSLUMA, call 1-844-POSLUMA (1-844-767-5862) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full POSLUMA prescribing information is available at www.posluma.com/prescribing-information.pdf.

On January 25, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported the closing of its previously announced underwritten public offering of 32,379,667 shares of its common stock, which includes 5,325,000 shares sold and issued upon the exercise in full by the underwriters of their option to purchase additional shares of common stock, and, in lieu of common stock to certain investors, pre-funded warrants to purchase 8,445,333 shares of common stock (Press release, Adicet Bio, JAN 25, 2024, View Source [SID1234639488]). The shares of common stock were sold at a public offering price of $2.40 per share and the pre-funded warrants were sold at a public offering price of $2.3999 per pre-funded warrant, which represents the per share public offering price of each share of common stock minus the $0.0001 per share exercise price for each pre-funded warrant. The aggregate gross proceeds from the offering, before deducting underwriting discounts and commissions and offering expenses, were approximately $98.0 million. All of the securities in the offering were sold by Adicet.

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Jefferies and Guggenheim Securities acted as joint book-running managers for the offering. Truist Securities also acted as a joint bookrunner. Wedbush PacGrow and JMP Securities, A Citizens Company acted as co-managers.

The securities described above were offered by Adicet pursuant to a shelf registration statement that was previously filed with, and subsequently declared effective on May 9, 2022 by, the U.S. Securities and Exchange Commission ("SEC"). A final prospectus supplement and accompanying prospectus relating to and describing the terms of the offering was filed with the SEC on January 24, 2024. Copies of the final prospectus supplement and the accompanying prospectus relating to the offered securities may be obtained from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected] or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On January 25, 2024 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported the presentation of updated dose escalation data from its Phase 1/2 study evaluating masofaniten (formerly EPI-7386) in combination with enzalutamide at the 2024 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium, taking place January 25 – 27, 2024, in San Francisco, CA (Press release, ESSA, JAN 25, 2024, View Source [SID1234639487]). Masofaniten is a first-in-class N-terminal domain androgen receptor ("AR") inhibitor that suppresses androgen activity through a novel mechanism of action and is being developed for the treatment of prostate cancer. The poster presentation is available on the "Publications" section of the Company’s website at www.essapharma.com.

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"The maturing data from the Phase 1 dose escalation study evaluating masofaniten in combination with enzalutamide continue to demonstrate that the combination is well tolerated, accompanied by deep and durable reductions in circulating prostate-specific antigen ("PSA") levels. While the data are still immature, the durability of the PSA responses is encouraging with a median time to PSA progression currently at 16.6 months. The Phase 2 dose expansion head-to-head portion of the study is underway and is designed to evaluate the proportion of patients with a PSA decline on combination therapy compared to single agent enzalutamide," said David Parkinson, MD, President and CEO of ESSA. "We look forward to evaluating the potential long-term benefits of masofaniten in patients with metastatic castration-resistant prostate cancer ("mCRPC") and to providing future updates."

Poster presentation details:

Title: Phase 1/2 trial of oral EPI-7386 (masofaniten) in combination with enzalutamide (Enz) compared to Enz alone in patients with metastatic castration-resistant prostate cancer (mCRPC): Phase 1 (P1) results and phase 2 (P2) design.
Presenting Author: Christos Kyriakopoulos, MD, University of Wisconsin-Madison Carbone Cancer Center
Abstract #: 141
Date and time: Thursday, January 25, 2024; 11:30-1:00 p.m. PT

Data summary: This Phase 1/2 multicenter, open-label clinical trial enrolled patients with mCRPC who have received androgen deprivation therapy and who are naïve to second-generation antiandrogens but may have been treated previously with one line of prior chemotherapy in the metastatic hormone-sensitive prostate cancer setting. The data presented today include 18 patients across four cohorts in the Phase 1 dose escalation portion of the study. Masofaniten has no effect on enzalutamide exposure, thus allowing the use of full dose per label (160mg) of enzalutamide in combination. Enzalutamide reduces masofaniten exposure but twice daily dosing of masofaniten appears to mitigate the reduction and maintains clinically relevant drug exposures.

In patients evaluable for safety (n=18), masofaniten combined with enzalutamide, continues to be well-tolerated at the dose levels tested through 25 cycles of dosing in some patients. Most frequent adverse events were Grades 1 and 2, related to either AR inhibition or gastrointestinal tract irritation. In Cohort 4, one patient experienced a Grade 3 rash, which was observed immediately following administration of masofaniten combined with enzalutamide and deemed probably related, resulting in the expansion of the cohort from four to seven patients. No additional dose-limiting toxicities (DLTs) were observed, therefore the maximum tolerated dose (MTD) was not reached. The recommended Phase 2 combination doses (RP2CDs) were identified as masofaniten 600 mg twice daily (BID) in combination with enzalutamide 160 mg once daily (QD).

In the patients evaluable for efficacy (n=16), rapid, deep and durable reductions in PSA were observed, regardless of previous chemotherapy status, including in patients who received lower than the full dose of enzalutamide (120 mg). Across all dose cohorts, 88% of patients (14 of 16) achieved PSA50, 81% of patients (13 of 16) achieved PSA90, 69% of patients (11 of 16) achieved PSA90 in less than 90 days, and 63% of patients (10 of 16) achieved PSA <0.2ng/mL. While the data for disease PSA progression are still maturing with a current median follow up of 11.1 months, the median time to PSA progression is at 16.6 months.

The randomized, open-label, two arm, Phase 2 dose expansion portion of the study is underway and is designed to evaluate the combination of masofaniten and enzalutamide versus single agent enzalutamide in patients with mCRPC naïve to second generation anti-androgens. The study is currently enrolling at approximately 25 sites in the USA, Canada and Australia. Expansion to European sites is in progress.

About Masofaniten
Masofaniten (formerly known as EPI-7386) is a first-in-class investigational, highly selective, oral, small molecule inhibitor of the N-terminal domain ("NTD") of the androgen receptor ("AR"). Masofaniten’s unique mechanism of action disrupts the AR signaling pathway, the primary pathway that drives prostate cancer growth, by selectively binding to the NTD, a region of the AR that is not currently targeted by other therapies. Masofaniten is currently being studied in an open-label, randomized Phase 2 clinical trial (NCT05075577) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) naïve to second-generation antiandrogens. ESSA is also conducting a Phase 1 monotherapy study (NCT04421222) in patients with mCRPC whose tumors have progressed on standard-of-care therapies. The U.S. Food and Drug Administration has granted Fast Track designation to masofaniten for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA retains all rights to masofaniten worldwide.

On January 25, 2024 Asieris Pharmaceuticals (Stock Code: 688176.SH), a global biopharmaceutical company specializing in discovering, developing, and commercializing innovative drugs for the treatment of genitourinary tumors and other related diseases, reported that the interim analysis data from the Phase II clinical trial of oral APL-1202 in combination with PD-1 inhibitor tislelizumab as neoadjuvant therapy for muscular invasive bladder cancer (MIBC) will be presented for the first time in the form of a rapid oral presentation abstract (Abstract No. 632) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) (Press release, Asieris Pharmaceuticals, JAN 25, 2024, View Source [SID1234639486]).

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Dr. Matt D. Galsky, MD, FASCO, from the Tisch Cancer Institute, Division of Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai, will be the speaker.