On June 5, 2023 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported updated results from BRACELET-1, a randomized phase 2 trial in HR+/HER2- metastatic breast cancer, which include data featured in an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, as well as additional new data and analyses (Press release, Oncolytics Biotech, JUN 5, 2023, View Source [SID1234632475]).

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BRACELET-1 enrolled 48 patients, including 45 that were randomized and well-balanced across three cohorts evaluating: (1) paclitaxel monotherapy; (2) paclitaxel in combination with pelareorep; and (3) paclitaxel plus pelareorep in combination with the anti-PD-L1 checkpoint inhibitor, avelumab (Bavencio). A three-patient safety run-in was also conducted with patients receiving pelareorep, paclitaxel, and avelumab prior to randomization. All participants enrolled in the trial had previously progressed on at least one hormone-based therapy with a CDK 4/6 inhibitor. No patients in BRACELET-1 received chemotherapy for metastatic disease prior to enrolling in the trial.

Updated data from BRACELET-1 showed a median progression-free survival (mPFS) of 9.5 months in the paclitaxel plus pelareorep cohort vs. 6.3 months in the paclitaxel monotherapy cohort for a hazard ratio of 0.29 as of a March 3, 2023 cut-off date. Confirmed overall response rate (ORR) in these cohorts was 37.5% and 13.3%, respectively. As previously reported, ORR at week-16 (the trial’s primary endpoint) in the pelareorep plus paclitaxel and paclitaxel monotherapy cohorts was 31.3% and 20%, respectively. Overall survival data from the trial continue to mature.

"BRACELET-1’s positive results complement prior phase 2 data showing a statistically significant increase in overall survival when pelareorep was combined with paclitaxel by demonstrating similar robust improvements in PFS and ORR in less heavily pre-treated patients," said Dr. Matt Coffey, President and Chief Executive Officer. "Given this exciting finding, our next step is to discuss our data with the FDA to investigate incorporating dual PFS and OS endpoints into our breast cancer program’s registrational study. Including a PFS endpoint could substantially reduce the time to a pivotal readout from the registrational trial, thereby accelerating pelareorep’s path to potential approval as we work to address the urgent needs of HR+/HER2- breast cancer patients."

A summary of response and PFS data from all 48 patients enrolled in BRACELET-1 is shown below.

Additional updated BRACELET-1 data 1:

Paclitaxel (PTX) Monotherapy (n=15) PTX + Pelareorep (n=16)
PTX + Pelareorep + Avelumab (n=17)2
Confirmed ORR Over Course of Trial 2 (13.3%) 6 (37.5%) 3 (17.6%)
mPFS (months)
6.3
(95% CI: 3.9, NR)
9.5
(95% CI: 6.5, NR)
6.2
(95% CI: 4.0, NR)
PFS Hazard Ratio vs. PTX Monotherapy -
0.29
(95% CI: 0.09, 0.98)
1.31
(95% CI: 0.47, 3.65)
12-month PFS Rate (%)
0
(95% CI: -, -)
32.8
(95% CI: 11.7, 92.4)
0
(95% CI: -, -)
1. Data from a March 3, 2023 cut-off date. Numbers presented may change as they are derived from an unlocked database.
2. Data include all patients enrolled in trial. Response data presented by Clark et al. at ASCO (Free ASCO Whitepaper) 2023 included the 45 randomized patients and excluded participants in the three-patient safety run-in in cohort 3.
CI: Confidence interval; NR: Not reached.

Key biomarker and safety findings from BRACELET-1 include:

•Association between T cell expansion and efficacy measures: A statistically significant increase in T cell fraction, a measure of T cell expansion, was observed in cohort 2 (paclitaxel + pelareorep) but not cohort 3 (paclitaxel + pelareorep + avelumab)
•Generally favorable and manageable safety profile: Pelareorep displayed a manageable safety profile consistent with what has been observed in prior clinical trials that have collectively treated over 1,100 patients

Dr. Thomas Heineman, Chief Medical Officer, commented, "BRACELET-1’s impressive initial results are maturing quite favorably. While five patients in the pelareorep-paclitaxel group had partial responses at week 16, six patients in total had confirmed responses. This includes two patients who improved from stable disease to partial responses at later times, consistent with pelareorep’s immunologic mechanism of action. Moreover, the compelling ORR and PFS hazard ratio achieved align with translational results showcasing pelareorep’s immune-mediated mechanism of action and complement additional data that support the combination therapy’s generally favorable safety profile. Collectively, these results bolster an expansive clinical dataset supporting the potential of pelareorep-paclitaxel combination therapy in HR+/HER2- metastatic breast cancer and are expected to propel our program to a pivotal licensure-enabling study."

A copy of slides from the ASCO (Free ASCO Whitepaper) oral presentation on BRACELET-1, titled "BRACELET-1 (PrE0113): Inducing an Inflammatory Phenotype in Metastatic HR+/HER2- Breast Cancer with the Oncolytic Reovirus Pelareorep in Combination with Paclitaxel and Avelumab," is available on the Posters & Publications page of Oncolytics’ website (LINK). Additional data and analyses from BRACELET-1 beyond those reported at the ASCO (Free ASCO Whitepaper) Annual Meeting will be available in the most recent investor presentation available by clicking here. Details of the key opinion leader webinar are shown below.

Key Opinion Leader Webinar
Oncolytics will host a key opinion leader (KOL) webinar featuring Richard Vile, Ph.D., (Mayo Clinic), Aleix Prat, M.D., Ph.D. (Clínic Barcelona), and Martine J. Piccart, M.D., Ph.D. (Université Libre de Bruxelles) today, June 5, 2023 at 8:00 a.m. ET. During the webinar, the KOLs and members of the Oncolytics management will discuss the current treatment landscape for HR+/HER2- metastatic breast cancer, as well as BRACELET-1’s results. A live question and answer session will follow a formal presentation and roundtable discussion with the KOLs. To register for the event, please click here.

About BRACELET-1
The BRACELET-1 (BReast cAnCEr with the Oncolytic Reovirus PeLareorEp in CombinaTion with anti-PD-L1 and Paclitaxel) study is an open-label, phase 2, randomized study in patients with HR+/HER2-, endocrine-refractory metastatic breast cancer. The study randomized 45 patients 1:1:1 into three cohorts. A three-patient safety run-in was also conducted with patients receiving pelareorep, paclitaxel, and avelumab prior to randomization. The three cohorts are treated as follows:

•Cohort 1: paclitaxel

•Cohort 2: paclitaxel + pelareorep

•Cohort 3: paclitaxel + pelareorep + avelumab (Bavencio)

Patients in cohort 1 receive paclitaxel on days 1, 8, and 15 of a 28-day cycle. Patients in cohort 2 receive the same paclitaxel regimen as cohort 1, plus pelareorep on days 1, 2, 8, 9, 15 and 16 of the 28-day cycle. Patients in cohort 3 receive the same combination and dosing regimen as cohort 2, plus avelumab on days 3 and 17 of the 28-day cycle. The primary endpoint of the study is overall response rate at week 16. Exploratory endpoints include progression-free survival, peripheral and tumor T cell clonality, inflammatory markers, and safety and tolerability assessments.

On June 5, 2023 Nerviano Medical Sciences S.r.l. (NMS), a clinical-stage biotechnology company member of NMS Group S.p.A. (NMS group), the largest cancer research and development company in Italy, reported signing of a license agreement and right of option with Solve Therapeutics, Inc. (SolveTx) to develop and commercialize novel antibody-drug conjugates (ADCs) for up to four cancer targets selected by SolveTx (Press release, Nerviano Medical Sciences, JUN 5, 2023, View Source [SID1234632474]).

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NMS is focused on discovery and development of innovative therapies for the treatment of cancer based on proprietary kinase and ADC linker-payload platforms, with approved targeted drugs licensed to pharma companies and proprietary innovative small molecules undergoing clinical studies. The development program will leverage NMS’s proprietary innovative linker-payload platform technology and SolveTx’s antibody-based oncology therapeutics technology. NMS’s linker-payload platform is carefully designed to generate more stable, efficacious, and safer ADCs to treat heterogenous and chemotherapy-resistant solid tumors. The licensed linker-payload includes optimized features; it can be readily conjugated to targeting antibodies, is highly active in preclinical in vitro and in vivo studies, shows bystander activity in heterogeneous tumors, promotes immune system recognition of tumor cells to induce immunogenic cell death, and demonstrates activity in chemotherapy-resistant and poorly proliferating tumors while maintaining a wide therapeutic index.

"We are excited to partner with SolveTx to extend our pipeline beyond our world-famous kinase platform and clinical assets to create novel drugs designed to target tumors more precisely and deliver more potent anticancer agents with our next‑generation linker-payload technology. The SolveTx team has a proven track record of developing transformative anticancer drug candidates and we are pleased that they have selected our linker-payload system for integration into their novel ADCs." said Hugues Dolgos, PharmD, Chief Executive Officer of NMS and NMS Group.

David Johnson, Founder and Chief Executive Officer of SolveTx, added "SolveTx is eager to explore use of NMS’s linker-payload as components of our ADCs. We feel that the NMS technology holds promise to overcome the limitations of current linker-payload systems and look forward to rapidly advancing our ADCs to benefit cancer patients in need."

Under the terms of the agreement, SolveTx will use NMS’s proprietary linker-payload technology to develop novel ADC product candidates for up to four targets selected by SolveTx. SolveTx will be responsible for the generation of targeting antibodies and all nonclinical, clinical, and commercialization activities relating to any resulting product candidates.

On June 5, 2023 IN8bio, Inc. (Nasdaq: INAB), a leading clinical-stage biopharmaceutical company focused on innovative gamma-delta T cell therapies, reported updated data from the ongoing Phase 1 clinical trial of INB-200 in patients with newly diagnosed glioblastoma multiforme (GBM) (Press release, In8bio, JUN 5, 2023, View Source [SID1234632473]). The data were featured as one-of-four oral presentations and the only Phase 1 study during the immunotherapy section of the Central Nervous System Tumors session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting in Chicago, Illinois.

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"The standard-of-care for GBM over the past twenty years falls short, with a median progression-free survival of just 4 to 7 months and overall survival of only 14 to 16 months. We are thrilled to see that two patients who have received three doses of INB-200 remain progression-free, clinically asymptomatic and off treatment for a prolonged period of time," said Trishna Goswami, M.D., Chief Medical Officer of IN8bio. "Further, the use of multiple doses in later cohorts have not led to a change in the toxicity profile, which may enable patients to stay on treatment longer and, ultimately, improve outcomes."

The oral presentation at ASCO (Free ASCO Whitepaper) includes efficacy and safety data as of a data cutoff of April 30, 2023. Eight patients have been treated with INB-200: three in Cohort 1 (single dose), four in Cohort 2 (three doses) and one in Cohort 3 (six doses). As of May 19, 2023 key findings from the ongoing study include:

Cohort 1 patients remained progression-free at 8.3, 11.9, and 7.4 months, with respective overall survival (OS) of 15.6, 17.7, and 9.6 months.
Two patients in Cohort 2 remain alive and progression-free at 23.5 and 19.4 months, respectively, exceeding median OS of GBM patients without progression.
In Cohort 3, the first patient dosed received five of six planned doses of gamma-delta T cells and had a progression-free survival (PFS) of 7.1 months and OS of 11.8 months with no evidence of additional toxicities. This patient who had an LZRT1 mutation experienced a rare leptomeningeal relapse, along with widespread relapse in their liver, lungs and pelvis. However, there was no progression in their brain, where INB-200 was administered.
No treatment-related deaths have been reported in any cohort. Six deaths were observed, three due to progression of disease and three unrelated to either treatment or progression (the deaths were due to sepsis, a cardiac event and pulmonary embolism).
No treatment-related serious adverse events (SAEs), dose-limiting toxicities (DLTs) cytokine release syndrome (CRS), infusion reactions, or immune effector cell-associated neurotoxicity syndrome (ICANS) have been reported in any cohort.
The most common treatment emergent adverse events (TEAEs) were white blood cell and platelet count decreases related to standard-of-care temozolomide, asthenia, headache and hydrocephalus, mostly Grade 1-2.
Three additional patients have been consented in Cohort 3 to date and are advancing through treatment.
"INB-200 has proven to be a safe and feasible method of delivering an innovative cell-based immunotherapy for newly diagnosed glioblastoma patients," said Dr. Burt Nabors, director of the Division of Neuro-Oncology in the University of Alabama at Birmingham Marnix E. Heersink School of Medicine.

The Company expects to provide further clinical updates later this year as study enrollment continues. The ASCO (Free ASCO Whitepaper) presentation titled "INB-200 Phase I Study of Gene Modified Autologous Gamma-Delta (γδ) T Cells in Patients with Newly Diagnosed Glioblastoma Multiforme (GBM) Receiving Maintenance Temozolomide (TMZ)" (Abstract #2007) can be found at View Source

About INB-200

INB-200 is a genetically modified autologous drug resistant immunotherapy (DRI) product candidate for the treatment of solid tumors. This novel platform utilizes genetic engineering to generate chemotherapy resistant gamma delta T cells which can be administered concurrently with standard-of-care treatment in solid tumors. This is a powerful, synergistic treatment approach is intended to enable gamma-delta T cells to persist in the presence of chemotherapy, and maintain their natural ability to recognize, engage and kill cancer cells.

INB-200 is the first genetically engineered gamma-delta T cell therapy to be administered to patients with solid tumors and our initial indication is in GBM.

On June 5, 2023 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, reported data from the Phase 3 ROMAN trial demonstrating avasopasem manganese (avasopasem) improved preservation of kidney function and reduced cisplatin-related chronic kidney disease (CKD) in patients with head and neck cancer (HNC) at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Galera Therapeutics, JUN 5, 2023, View Source [SID1234632472]). Patients in the ROMAN trial received standard-of-care radiation therapy with concurrent cisplatin. These kidney results are in addition to the ROMAN data showing a significant reduction in severe oral mucositis (SOM) in these patients, which form the basis of the avasopasem New Drug Application (NDA) currently under priority review with the U.S. Food and Drug Administration (FDA).

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"The demonstrated improvement in kidney function and reductions in cisplatin-related CKD following treatment suggest that avasopasem has the potential to significantly reduce known kidney toxicities associated with cisplatin and other platinum-based chemotherapies," said Mel Sorensen, M.D., Galera’s President and CEO. "In addition to a reduction in reported renal toxicity adverse events during treatment, benefits to kidney function were observed soon after cessation of cisplatin therapy, with CKD reduced by 50 percent in the avasopasem treatment arm at one year, regardless of cisplatin dosing schedule. Our Phase 3 ROMAN trial demonstrated avasopasem’s ability to reduce SOM, a debilitating toxicity induced by radiotherapy, and our NDA for this indication is currently under FDA priority review. The pre-specified exploratory analysis of CKD presented at ASCO (Free ASCO Whitepaper) suggests a potential additional protective clinical benefit for patients undergoing treatment with cisplatin in multiple cancers."

Highlights from the Phase 3 ROMAN data presented at ASCO (Free ASCO Whitepaper):

Avasopasem was associated with significant improvements in preservation of kidney function compared to placebo based on mean change in estimated Glomerular Filtration Rate (eGFR) compared to baseline, beginning by 3 months through the one-year end of follow-up
Avasopasem was associated with a significant reduction in incidence of grade 3+ CKD according to KDIGO1 criteria (eGFR <60 mL/min/1.73m2)
10% of patients treated with avasopasem had grade 3+ CKD, compared to 20% of patients in the placebo arm at one-year follow-up (relative risk 0.55, p=0.0043)
Reductions in CKD were consistent across cisplatin dosing schedules
Avasopasem was associated with reduced incidence of cisplatin-related renal adverse events during treatment
This prospectively-defined exploratory analysis of the Phase 3 ROMAN trial included patients undergoing the standard-of-care regimen of intensity-modulated radiation therapy (IMRT) with concurrent cisplatin. The effect of avasopasem on kidney function was assessed throughout treatment and every three months for one year following seven weeks of therapy. Grade 3+ CKD was defined as eGFR <60 mL/min/1.73m2.

The presentation is available on Galera’s website at View Source

About Avasopasem
Avasopasem manganese 90 mg (avasopasem, or GC4419) is a selective dismutase mimetic in development for the reduction of radiotherapy-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (HNC) and for the reduction of radiotherapy-induced esophagitis in patients with lung cancer. The FDA has granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of SOM induced by radiotherapy. Avasopasem is currently under FDA priority review for radiotherapy-induced SOM in patients with HNC undergoing standard-of-care treatment.

On June 5, 2023 Domain Therapeutics ("Domain" or "the Company"), a clinical-stage biopharmaceutical company developing innovative drug candidates in immuno-oncology targeting G Protein-Coupled Receptors (GPCRs), reported the nomination of a drug candidate, a Negative Allosteric Modulator (NAM) of protease-activated receptor 2 (PAR2), DT-9045, with first-in-class potential for immuno-oncology, particularly for fibrotic tumors (Press release, Domain Therapeutics, JUN 5, 2023, View Source [SID1234632471]).

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Domain carefully selects its immuno-oncology assets using its proprietary cross-validation platform that includes preclinical and clinical data to identify and validate GPCR targets involved in immunosuppressive mechanisms. Through this precision research strategy, backed by two decades of deep-expertise in understanding GPCRs, the Company has developed a novel series of potent and selective PAR2 NAMs. PAR2 is a novel therapeutic target in oncology and immuno-oncology, involved in several processes such as tumor proliferation, resistance to immunotherapy and fibrosis.

Domain nominated DT-9045 as a first-in-class PAR2 NAM clinical candidate based on its added-value, unique properties and greater therapeutic potential in comparison to biologics targeting PAR2 currently in the clinic by several competitors. DT-9045 has demonstrated proof-of-concept efficacy in syngeneic models potentiating the anti-tumor activity of an anti-PD1 treatment.

The Company’s PAR2 NAM approach is particularly advantageous compared to competitors due to its unique pharmacological features:

G-protein biased NAM activity on PAR2 (with no impact on the b-Arrestin pathway and ligand-induced receptor internalization),
unsurmountable property enabling preservation of efficacy even at high concentrations of ligand that could be found in the tumor microenvironment
activity maintained at acidic pH, typical to inflammatory and tumoral environment
Domain has established a clear biomarker strategy guiding the clinical positioning for DT-9045 and with pre-IND studies in progress, the Company’s expectations are for Phase I ascending dose studies in recurrent or metastatic solid tumors to start by mid-2025.

Dr. Pascal Neuville, CEO of Domain Therapeutics, commented: "The nomination of our first-in-class PAR2 NAM drug candidate, DT-9045, is an exciting step forward for Domain Therapeutics and for cancer treatment in general. With its unique features of modulating the immune system response and playing a role in immunosuppression triggered by the tumor, this asset shows unmatched potential to expand the responsiveness of immunotherapy and increase the success rate of non-responding patients. Applying our precision research, we are making steady progress in building our portfolio of assets with best-in-class and first-in-class potential. We look forward to bringing DT-9045 to the clinic by mid-2025 as we work to unlock new cancer treatment possibilities."

Dr. John Stagg, Principal investigator at the Centre Hospitalier de l’Université de Montréal (CHUM), Canada and Member of Domain Therapeutic’s Scientific Advisory Board, commented: "Working closely with Domain, we were able to identify the PAR2 therapeutic target that can potentially pave the way to new GPCR-based immunotherapies and deliver more efficient therapeutic strategies for cancer patients. I look forward to advising the team through the next stages to progress the clinical development of DT-9045 through our fruitful collaboration."

Furthermore, Cancer Associated Fibroblasts (CAF) are involved in fibrosis mediated immunoresistance leading to failure of several therapies in the clinic. The role of PAR2 in CAF modulation opens a novel therapeutic avenue for the treatment of solid tumors, including those involving fibrosis such as pancreatic or lung cancers.