On September 22, 2025 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from the phase III evERA study evaluating investigational giredestrant in combination with everolimus in people with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy (Press release, Hoffmann-La Roche, SEP 22, 2025, View Source [SID1234656151]). The study met both co-primary endpoints, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in both the intention-to-treat and ESR1-mutated populations, compared with standard-of-care endocrine therapy plus everolimus. Overall survival (OS) data were immature, but a clear positive trend was observed. Follow-up continues to the next OS analysis. The giredestrant combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments, and no new safety signals were observed. This is the first positive head-to-head phase III trial investigating an all-oral selective oestrogen receptor degrader-containing regimen versus a standard of care combination.

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"These results show that the giredestrant combination provided a meaningful benefit for ER-positive breast cancer patients whose disease has progressed following treatment with a CDK inhibitor," said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. "We look forward to discussing these results with regulatory authorities with the goal of making this giredestrant-based regimen available to many people with advanced ER-positive breast cancer."

ER-positive breast cancer accounts for approximately 70% of breast cancer cases.2 Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity.3 Resistance to endocrine therapies, particularly in the post-CDK inhibitor setting, increases the risk of disease progression and is associated with poor outcomes.2,4 Combination therapies, such as giredestrant plus everolimus, could address this by targeting two different signalling pathways, with the potential for improved patient outcomes.3 Additionally, as an all-oral combination, this regimen could help minimise the impact of treatment on people’s lives without the need for injections.5

Our extensive giredestrant clinical development programme spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.

Data from the evERA study will be submitted to health authorities with the view of bringing this potential treatment option to patients as soon as possible.

About the evERA Breast Cancer study
evERA Breast Cancer [NCT05306340] is a phase III, randomised, open-label, multicentre study evaluating the efficacy and safety of giredestrant in combination with everolimus versus standard-of-care endocrine therapy in combination with everolimus in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase 4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.1

The co-primary endpoints are investigator-assessed progression-free survival in the intention-to-treat and ESR1-mutated populations, defined as the time from randomisation to the time when the disease progresses or a patient dies from any cause. The trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to 40% of people with ER-positive disease have ESR1 mutations4. Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and safety.1

About giredestrant
Giredestrant is an investigational, oral, next-generation selective oestrogen receptor degrader (SERD) and full antagonist.6

Giredestrant is designed to block oestrogen from binding to the oestrogen receptor (ER), triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.7,10-12

Giredestrant has an extensive clinical development programme and is being investigated in five company-sponsored phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)13
Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)1
Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)14
Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor versus fulvestrant plus a CDK 4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)15
Giredestrant plus Phesgo (pertuzumab, trastuzumab, and hyaluronidase subcutaneous) versus Phesgo in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)16
About oestrogen receptor (ER)-positive breast cancer
Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year.17 Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.18

ER-positive breast cancer accounts for approximately 70% of breast cancer cases.2 A defining feature of ER-positive breast cancer is that its tumour cells have receptors that attach to oestrogen, which can contribute to tumour growth.19

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity.3 Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy.3,20 There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

On September 22, 2025 Sartar therapeutics reported it was recently granted an new orphan drug designation (ODD) by the U.S. Food & Drug Administration (FDA) for the treatment of soft tissue sarcomas using its SAR003 drug candidate (Press release, Sartar Therapeutics, SEP 22, 2025, View Source [SID1234656150]). This is a great milestone for its team and a significant regulatory protection for SAR003 program. Sartar has previously received ODDs for SAR003 for the treatment of gastrointestinal stromal tumours (GIST) by both EMA and FDA.

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Now it has the ODD protection for SAR003 for the treatment of all soft tissue sarcomas in the US.

On September 22, 2025 Haystack Oncology, a Quest Diagnostics (NYSE: DGX) company, reported a research collaboration with the Rutgers Cancer Institute to evaluate the use of Haystack MRD, a highly sensitive circulating tumor DNA (ctDNA) minimal residual disease (MRD) test, to help optimize postoperative therapy decisions in patients with stage II/III non-small cell lung cancer (NSCLC) (Press release, Quest Diagnostics, SEP 22, 2025, View Source [SID1234656149]). Rutgers Cancer Institute together with RWJBarnabas Health is the state’s only National Cancer Institute-designated Comprehensive Cancer Center.

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"Trial of ctDNA Guidance to Determine Post Operative Radiation Therapy (PORT) for Minimal Residual Disease (MRD) for Lung Cancer: the MRD-PORT Trial (NCT06979661)" is a prospective phase II study that will use the Haystack MRD test to assess whether the presence of residual tumor DNA after surgery can help guide the use of radiation and systemic therapies.

"Circulating tumor DNA is a pivotal marker to figure out how best to individualize patient care for lung cancer," said Salma Jabbour, MD, Vice Chair of Clinical Research and Faculty Development, Department of Radiation Oncology and Associate Director Faculty Affairs and Development, Rutgers Cancer Institute. "Studying new ways to detect this marker are important for helping improve patient outcomes."

Personalizing postoperative therapy in NSCLC

The study will evaluate ctDNA in patients with stage II/III NSCLC in the adjuvant setting. Patients who test positive for ctDNA after surgery—indicating potential residual disease—will be considered for adjuvant radiation and systemic therapy, including chemotherapy, immunotherapy, or targeted therapy, based on tumor biology and clinical context.

"The ability to identify residual disease following curative-intent treatment opens the door to more precise, personalized interventions, moving us closer to truly individualized cancer care," said Dan Edelstein, Vice President and General Manager of Haystack Oncology. "While existing data supports the prognostic value of ctDNA in lung cancer, this innovative study will now address the question of how ctDNA-based testing can guide and optimize adjuvant treatment decisions."

The study is the second by Rutgers Cancer Institute involving Haystack MRD. In 2023, the two parties announced a study to evaluate the test for use in patients being treated for early-stage triple-negative breast cancer.

Why ctDNA MRD matters

A growing body of research underscores the potential role of ctDNA MRD tests to identify residual or recurring cancer in patients with solid tumors. In April 2025, a study1 published in The New England Journal of Medicine (NEJM) found that ctDNA testing, using Haystack MRD, was a "reliable liquid biopsy surrogate" that identified clinical complete response at a median of 1.4 months compared to over 6 months using imaging tests. Nearly all oncologists (96%) in a recent survey2 by Harris Poll for Quest Diagnostics said MRD testing has the potential to identify cancer recurrence earlier than other current methods. In August 2025, the FDA granted Breakthrough Device Designation to Haystack MRD for identifying MRD-positive patients with stage II colorectal cancer following curative-intent surgical treatment who may benefit from adjuvant therapy in accordance with therapeutic product labeling.

About Lung Cancer

Lung cancer is the leading cause of cancer-related deaths in the U.S3. Despite advances in surgery and systemic therapies, recurrence rates remain high, especially for patients with stage II and III NSCLC.4 Studies show that patients who test positive for ctDNA after surgery have dramatically worse progression-free survival and overall survival compared to ctDNA-negative patients.

On September 22, 2025, Nuvalent, Inc. reported the completion of its New Drug Application submission to the U.S. Food and Drug Administration for zidesamtinib in tyrosine kinase inhibitor pre-treated patients with advanced ROS1-positive non-small cell lung cancer (Press release, Nuvalent, SEP 22, 2025, View Source [SID1234656148]).

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On September 22, 2025 IMUNON, Inc. (Nasdaq: IMNN), a clinical-stage company in Phase 3 development with its DNA-mediated immunotherapy, reported the presentation of new positive translational data from the Phase 2 OVATION 2 Study of IMNN-001, its investigational gene-based interleukin-12 (IL-12) immunotherapy based on the Company’s proprietary TheraPlas technology platform, for the treatment of newly diagnosed advanced ovarian cancer (Press release, IMUNON, SEP 22, 2025, View Source [SID1234656147]). Results were highlighted in a presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference in Cancer Research: Advances in Ovarian Cancer Research held in Denver, Colorado.

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The Phase 2 OVATION 2 Study assessed 112 participants treated with IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus standard-of-care (SoC) neoadjuvant and adjuvant chemotherapy (N/ACT). IMUNON reviewed translational data on the changes induced by the local administration of IL-12 and its downstream effectors in the tumor micro-environment (TME) from paired samples (pre- and post-treatment) from study participants. Results presented at the AACR (Free AACR Whitepaper) Special Conference demonstrated:

Positive shift in the local TME to favorable immune stimulatory T cell ratios in the majority of participants treated with IMNN-001, including favorable ratios of CD8+/T regulatory (Treg) cells, CD8+/IDO+ cells, and CD8+/CD4+ cells.
TME shift in favor of decreased immunosuppression cells (IDO+, PDL1+, Treg, CD4+) and increased immunostimulatory cells (CD8+, CD8+ effector, myeloid dendritic cells) in the majority of participants post-treatment.
IMNN-001 treatment creates a "hot" anti-TME by increasing the recruitment of anti-tumor CD8+ and myeloid dendritic cells in 50-80% of the paired samples and decreasing immunosuppressive markers (IDO, PDL1, Treg cells) in 65-80% of the samples.
IMNN-001 continues to show a favorable safety profile.
"These new translational data are very encouraging and strongly reinforce and are consistent with the unprecedented positive overall survival results previously reported from the OVATION 2 Study," said Douglas V. Faller, M.D., Ph.D., Chief Medical Officer of IMUNON and study presenter at the AACR (Free AACR Whitepaper) conference. "Results from the study continue to validate our TheraPlas technology and the broad impact of IMNN-001 on important cancer-fighting cytokines, effectively turning the tumor microenvironment from "cold" to ‘hot’ by activating both innate and adaptive immune systems, with limited to no systemic toxicities. IMNN-001 has shown significant therapeutic potential in clinical trials thus far, and the robust survival benefits and favorable safety profile observed align with these translational findings, supporting our ongoing Phase 3 OVATION 3 trial. We look forward to advancing the Phase 3 trial as quickly as possible for the many women with advanced ovarian cancer who are in urgent need of new, innovative treatment options."

The OVATION 2 Study poster presentation is available on the "Scientific Presentations" page of IMUNON’s website at View Source

In July 2025, the Company announced treatment of the first patient in the pivotal Phase 3 OVATION 3 Study and is working with trial investigators to expand clinical sites and accelerate enrollment. Four sites have been activated to date and are open for patient enrollment.

About the OVATION 3 Study

OVATION 3 is IMUNON’s pivotal Phase 3 study of IMMN-001, an IL-12 gene-mediated immunotherapy, in women with advanced epithelial ovarian cancer. The study is supported with unprecedented overall survival (OS) data from a large, 112-patient, randomized Phase 2 study showing the following:

Median 13-month increase in OS (HR 0.70) and median 3-month increase in PFS (HR 0.79) in IMNN-001 treatment arm compared to standard of care alone.
Better therapeutic effect observed with IMNN-001 treatment compared to the control arm (p=0.0375), as shown by mean 6.5-month extension of time free of progression or death (PFS + OS) captured in totality of treatment effect.
Use of poly ADP-ribose polymerase (PARP) inhibitors as part of maintenance therapy further enhanced outcomes, with median OS not yet reached in the IMNN-001 treatment arm as patients surpass >5 years since randomization in the trial compared to 37 months on standard of care (HR 0.42).
The results from the OVATION 2 Study have resulted in invitations to present data from the Phase 2 Study at both the ASCO (Free ASCO Whitepaper) and ESMO (Free ESMO Whitepaper) annual meetings and in the peer-reviewed journal Gynecologic Oncology.

OVATION 3 is currently enrolling patients at four trial sites with up to 46 additional sites being considered for activation.

About the Phase 2 OVATION 2 Study

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (N/ACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following N/ACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare N/ACT plus IMNN-001 versus standard-of-care N/ACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to N/ACT. As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response score.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer. IMUNON previously reported positive results from the recently completed Phase 2 OVATION 2 Study, which assessed IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (N/ACT) of paclitaxel and carboplatin compared to standard-of-care N/ACT alone in 112 patients with newly diagnosed advanced ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.