1stOncology™: Cancer Intelligence Service – Page 3370 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Sermonix Pharmaceuticals Shares Pharmacokinetic and Baseline Genomic Clinical Data Tied to ELAINE Lasofoxifene Trials of Patients With ESR1 Mutations

On December 12, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC) harboring ESR1 mutations, reported the three poster presentations examining clinical data tied to Sermonix’s Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) studies (Press release, Sermonix Pharmaceuticals, DEC 12, 2023, View Source [SID1234638576]). The presentations were initially shared last week at the 2023 San Antonio Breast Cancer Symposium (SABCS).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"Secondary analysis of our ELAINE study results reveals reassuring pharmacokinetic data, further confidence in lasofoxifene’s ability to be effectively combined with abemaciclib, and a better understanding of the baseline genomic alterations found in patients with ESR1 mutations," said Dr. Paul Plourde, Sermonix vice president for clinical oncology development. "We are delighted to be actively screening and enrolling patients into our Phase 3 ELAINE-3 registrational trial at institutions across the U.S., and with the EU to closely follow."

One poster addressed pharmacokinetics (PK) of lasofoxifene as a monotherapy and in combination with Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib (Verzenio). Key takeaways included:

PK data for lasofoxifene 5 mg/day were consistent with previous clinical trials, resulting in similar steady-state concentrations in patients across several studies.
Addition of abemaciclib to lasofoxifene did not appear to alter the PK of lasofoxifene in ELAINE-2 compared with monotherapy in ELAINE-1, suggesting little to no drug-drug interaction.
Abemaciclib concentrations in ELAINE-2 were consistent with previous monotherapy data, suggesting no impact of lasofoxifene on abemaciclib PK.
A second poster discussed baseline genomic alterations and the activity of lasofoxifene and abemaciclib during the ELAINE-2 study. Key results/conclusions included:

In 26 of the 29 patients (median age 60 years) enrolled, ESR1 mutations were identified at baseline by the Guardant360 CDx test. The profiling demonstrated that other genomic alterations are frequently detected concurrently with ESR1 mutations in the endocrine-resistant setting, in line with previous findings among patients with hormone receptor-positive mBC.
Co-alterations in ESR1 and other genes associated with treatment resistance did not appear to compromise the efficacy of lasofoxifene plus abemaciclib in ELAINE-2.
A third poster offered a trial-in-progress update on ELAINE-3, a 400-patient Phase 3 study assessing the efficacy and safety of lasofoxifene in combination with abemaciclib in treating locally advanced or ER+/HER2- mBC with an ESR1 mutation. ELAINE-3 enrollment is now underway.

To learn more about Sermonix Pharmaceuticals and lasofoxifene, visit View Source For more information about the ELAINE studies, visit View Source

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

Obsidian Therapeutics Announces Positive Interim Top-Line Clinical Data for OBX-115 Engineered TIL Cell Therapy in Advanced or Metastatic Melanoma Post-Anti-PD1 Therapy

On December 12, 2023 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported positive top-line results from the ongoing first-in-human, Phase 1 clinical trial evaluating the safety and efficacy of OBX-115, Obsidian’s lead engineered tumor-infiltrating lymphocyte (TIL) cell therapy candidate, in patients with metastatic melanoma that has relapsed and/or is refractory to prior immune checkpoint inhibitor (ICI) therapy (NCT05470283) (Press release, Obsidian Therapeutics, DEC 12, 2023, View Source [SID1234638520]).

OBX-115 is an investigational novel IL2-sparing engineered TIL cell therapy armed with pharmacologically regulatable membrane-bound IL15 designed to enhance persistence, anti-tumor activity, and clinical safety of TIL cell therapy relative to unengineered TIL therapy plus high-dose IL2.

The first six patients treated with OBX-115 were enrolled by Rodabe Amaria, M.D., professor of Melanoma Medical Oncology and principal investigator of the study at The University of Texas MD Anderson Cancer Center. Patients were heavily pre-treated, and all had progressed on anti–PD-1 and anti–CTLA-4 therapy with disease that was primary-resistant to ICI therapy. At a median follow-up of 18 weeks (December 1st, 2023 data cut-off), a 50% investigator-assessed objective response rate (ORR) using RECIST 1.1 criteria was observed. Two complete responses and one partial response were achieved, with a disease control rate (DCR) of 100%.

To date, no dose-limiting toxicities have been observed, and the treatment-emergent adverse event profile was consistent with that of lymphodepletion. OBX-115 was manufactured from core-biopsies of tumors for the majority of patients by CTMC, a joint venture between MD Anderson and National Resilience, Inc. Additionally, early data from the study support validation of Obsidian’s cytoDRiVE technology for the pharmacologic regulation of membrane-bound IL15 to enable controlled proliferation, enhanced persistence and anti-tumor activity of adoptive T-cell therapies.

"The OBX-115 data show its potential to be a meaningful advancement in the treatment of metastatic melanoma and TIL cell therapy," said Parameswaran Hari, M.D., M.S., Chief Development Officer of Obsidian Therapeutics. "These initial topline results support the promise for OBX-115 to drive responses in this heavily pre-treated patient population and facilitate the expansion of TIL cell therapy in melanoma to a broad group of patients without the need for IL2."

In addition, Obsidian announced today that it has enrolled the first patient in its multicenter Phase 1/2 study of advanced or metastatic melanoma resistant to ICI therapy. This study allows multiple centers to have access to OBX-115 and is currently enrolling patients. Additional details may be found at clinicaltrials.gov, using identifier: NCT06060613.

"These positive results underscore the potential for OBX-115 TIL cell therapy to offer patients with metastatic melanoma a differentiated TIL therapy without the need for IL2," said Madan Jagasia, M.D., M.S., CEO of Obsidian Therapeutics. "Furthermore, the emerging profile of OBX-115 indicates it will allow expansion of TIL cell therapy into a broad patient population, including those who may not be able to tolerate IL2 or choose not to receive it. As we look to the future, we are exploring additional indications, including non-small cell lung cancer."

About OBX-115
Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-infiltrating lymphocyte (TIL) cell therapy armed with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, anti-tumor activity, and clinical safety of TIL cell therapy. OBX-115 is being investigated in two ongoing and enrolling clinical trials in advanced or metastatic melanoma (NCT05470283 and NCT06060613).

Toragen, Inc. Announced Positive Safety Data Update from Cohort 2 and the Initiation of its Dose Expansion of its Phase 1 Trial in Patients with Human Papillomavirus-Induced Cancer

On December 12, 2023 Toragen Inc., a San Diego-based clinical-stage biotechnology company focused on developing uniquely selective drugs targeting cancers caused by viruses, reported positive safety data from Cohort 2 of its Phase 1 trial of TGN-S11, its first drug candidate, in patients with HPV-associated cancers (Press release, Toragen, DEC 12, 2023, View Source [SID1234638519]).

This Phase 1 trial is an open-label, non-randomized study in cohorts of patients with relapsed, resistant, or metastatic HPV-associated cancers. The study is being conducted in two parts: a dose escalation part and dose expansion part. The dose escalation consists of five Cohorts of three to six patients. The dose expansion will now begin in parallel with Cohort 3 of the dose escalation. Level 1 of the dose expansion part of the Phase 1 trial will be in combination with a PD-1 checkpoint inhibitor.

"Having this early safety signal for our dose escalation portion of our Phase 1 trial is yet another early milestone for Toragen," said Dr. Sandra Coufal, Toragen’s CEO. "By beginning the dose expansion portion of the Phase 1 trial in an accelerated timeframe, we bring hope of meeting an unmet medical need for HPV-cancer patients by possibly enhancing the efficacy of the PD-1 checkpoint inhibitor."

Ankyra Therapeutics Announces Pre-Clinical Research Published in December JCI Insight Demonstrating Potent Anti-Tumor Activity of Anchored IL-12 in Multiple Murine Cancer Models

On December 12, 2023 Ankyra Therapeutics, an emerging clinical-stage biotechnology company pioneering anchored immunotherapies to treat cancer, reported results from a preclinical study demonstrating potent anti-tumor activity of its lead program ANK-101 were published in the December issue of the Journal of Clinical Investigation Insight (JCI Insight) (Press release, Ankyra Therapeutics, DEC 12, 2023, View Source [SID1234638518]). The research paper is titled "Intratumoral aluminum hydroxide-anchored IL-12 drives potent antitumor activity by remodeling the tumor microenvironment."

ANK-101 is a novel tumor-directed anchored immune medicine (AIM) composed of interleukin-12 (IL-12) linked to aluminum hydroxide.

"One of the key challenges of intratumoral administration is retention within the tumor, both for efficacy and to limit systemic exposure," said Howard L. Kaufman, M.D., President and Chief Executive Officer of Ankyra Therapeutics. "Our pre-clinical data indicates that anchored immunotherapy retains active IL-12 at the tumor site for weeks, versus just hours with unanchored recombinant IL-12. This results in potent immune activation with limited systemic exposure, indicating the potential to improve patient outcomes while reducing side effects. We are excited to continue to advance this program and look forward to initiating our Phase 1 clinical study in humans in early 2024."

Data published in JCI showed:

Ankyra’s anchored immunotherapy platform achieves retention of the drug ANK-101 at the injected site for approximately four weeks
One or two intratumoral injections of a murine ANK-101 analogue induced single-agent anti-tumor activity across a diverse range of syngeneic mouse models
Local treatment with the drug induced tumor regressions of distant, non-injected lesions demonstrating abscopal effects, which were enhanced when combined with systemic checkpoint blockade
Anti-tumor activity mediated by the drug was associated with recruitment of immune cells and remodeling the tumor microenvironment
Human ANK-101, when tested in cynomolgus macaques, was well tolerated
About ANK-101
ANK-101 is an anchored drug complex composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local delivery of functional IL-12 to the tumor microenvironment where it remains biologically active for several weeks, but does not diffuse into the systemic circulation, thereby avoiding systemic toxicity. Treatment with ANK-101 in animal models has been associated with recruitment of CD8+ T cells, NK cells and M1 macrophages activating innate and adaptive anti-tumor immunity. ANK-101 is being evaluated for the treatment of advanced solid tumors alone and in combination with anti-PD-1 agents.

City of Hope presents pivotal clinical trial data at American Society of Hematology (ASH) conference on revumenib, a potential new targeted therapy for high-risk subtypes of acute leukemias

On December 12, 2023 City of Hope, one of the largest cancer research and treatment organizations in the United States, reported that 23% of patients with relapsed or treatment-resistant KMT2Ar AML, ALL and mixed phenotype leukemia who took revumenib in the AUGMENT-101 multicenter clinical trial had a complete remission (CR) — the cancer went into remission with complete recovery of peripheral blood counts — or a CRh — the cancer went into remission and there was partial recovery of peripheral blood counts (Press release, City of Hope, DEC 12, 2023, View Source [SID1234638517]). The data was presented as a late-breaking abstract at ASH (Free ASH Whitepaper) and in a press briefing. Revumenib is a highly selective inhibitor of the menin-KMT2A binding interaction that is being developed by Syndax Pharmaceuticals.

"We look forward to submitting a new drug application to the U.S. Food and Drug Administration for revumenib for the treatment of R/R KMT2Ar acute leukemia by year-end, with the goal of efficiently bringing this treatment to patients who need it most."

Post this
These 13 patients with CR or CRh also stayed in remission for an average of 6.4 months, with six patients still remaining in remission at the time the data was collected. Trial participants had an overall response rate (ORR) of 63%, or 36 out of 57 patients, meaning they had a partial or complete clearance of the leukemia in response to the therapy with or without blood count recovery.

"The only current treatment plan for adult and pediatric patients with these types of relapsed or treatment-resistant leukemias is chemotherapy to achieve temporary remission as a path to a bone marrow or stem cell transplant. But fewer than 10% of these patients respond to the chemotherapy, and the expectation for survival is in the range of three months," said Ibrahim Aldoss, M.D., City of Hope associate professor in the Division of Leukemia within the Department of Hematology & Hematopoietic Cell Transplantation and principal investigator for the AUGMENT-101 trial. "What this trial demonstrates is that revumenib did work safely and effectively in varying degrees in a majority of trial participants and had induced deep remissions in the majority of responders, giving us hope about the prospect of an additional, urgently needed treatment option, as well as a therapy that can help these patients to receive a curative bone marrow or stem cell transplant."

Thirty-nine percent of patients who had ORR, or 14 total, were able to successfully receive a bone marrow or stem cell transplant — the only treatment that can cure these leukemia types — while their cancer was in remission with the therapy. Aldoss explained that this finding is important since patients with these leukemias cannot have a transplant if their bone marrow continues to have disease. In addition, half of transplanted patients took revumenib after a transplant as a maintenance therapy to reduce the chance of leukemia relapsing.

The study enrolled 92 patients with KMT2Ar leukemias, including children, adults and older adults, with various leukemia subtypes (AML, ALL and mixed phenotype leukemia). Fifty-seven patients in the largest group had their KMT2Ar finding confirmed by a central laboratory, and they were considered for the study’s efficacy endpoint.

"We are thrilled to present additional detail on the positive results for revumenib in KMT2Ar acute leukemia that continue to demonstrate its consistently compelling clinical profile as a potential monotherapy for these heavily pretreated patients with high unmet need," said Michael A. Metzger, chief executive officer of Syndax. "We look forward to submitting a new drug application to the U.S. Food and Drug Administration for revumenib for the treatment of R/R KMT2Ar acute leukemia by year-end, with the goal of efficiently bringing this treatment to patients who need it most."

Aldoss noted that revumenib produced comparable response rates in patients of different ages and leukemia subtypes.

Tatum Demontmorency, 19, participated in the clinical trial at City of Hope after she was diagnosed with leukemia in 2021. The Bakersfield, California, resident began to feel weak and fatigued, and at first, doctors suspected a viral infection like mononucleosis. Demontmorency later started to experience severe stomach pain.

After more bloodwork and a computed tomography (CT) scan, she was diagnosed with AML with KMT2Ar. She was treated with standard chemotherapy, but unfortunately her leukemia returned later. Demontmorency and her family were advised to travel to Los Angeles for cancer treatment, and she eventually sought care at City of Hope’s Children’s Cancer Center, where she enrolled in the revumenib trial. The therapy, an oral pill that is taken twice a day in a 28-day cycle, cleared all her detectable cancer, and Demontmorency was able to receive a stem cell transplant from her brother, Trey.

Demontmorency is now a sophomore at Bakersfield College, has her eye on a career in health care, possibly as an ultrasound technician, and has returned to playing volleyball. She also coaches the team at her old high school.

"Tatum’s story is truly inspirational, and our hope is that revumenib will continue to make it possible for our patients with these types of leukemias to continue with their lives," Aldoss added.

Among trial participants, the therapy was safe and tolerable, with the most common side effects of nausea, differentiation syndrome and reversible changes in electrocardiogram. Patients tolerated these and other side effects well as only 6% of patients left the trial due to treatment-related adverse effects.

If approved for use by the FDA, the product would be the first therapy to target what’s known as the menin-KMT2A interaction. Menin is a protein that binds to KMT2A, a genetic defect, and this interaction causes KMT2Ar AML and ALL to accumulate abnormal cells in the bone marrow and blood. Revumenib can prevent this interaction from occurring, leading to possible cancer remission.