On June 2, 2025 Genmab A/S (Nasdaq: GMAB) reported new data from cohort B2 of the Phase 1/2 RAINFOL-01 trial evaluating rinatabart sesutecan (Rina-S), an investigational folate receptor alpha (FRα)-targeted, TOPO1-inhibitor antibody-drug conjugate (ADC). The study showed that with a median on-study follow-up of 7.7 months, treatment with Rina-S 100 mg/m2 every 3 weeks (Q3W) resulted in a 50.0 percent confirmed objective response rate (ORR), including two complete responses (CR), in heavily pre-treated advanced endometrial cancer (EC) patients who experienced disease progression on or after treatment with platinum-based chemotherapy and an immune checkpoint inhibitor (Press release, Genmab, JUN 2, 2025, View Source [SID1234653606]). The median duration of response (mDOR) was not reached. These data are from the endometrial cancer monotherapy dose expansion B2 cohort of the multi-part RAINFOL-01 trial evaluating the safety and efficacy of Rina-S in solid tumors and were presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois.

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"Advanced stage and recurrent endometrial cancer often lead to resistance to standard of care options. When this occurs, prognosis worsens and treatment options become increasingly limited, leaving patients and clinicians to navigate difficult decisions," said Ira Winer, M.D., Ph.D., FACOG, study investigator and Professor, Division of Gynecologic Oncology and Phase I Developmental Therapeutics at the Karmanos Cancer Institute, Wayne State University. "These Phase 1/2 results demonstrate encouraging data with Rina-S in this patient population and support its further development as a potential therapy for patients with advanced and recurrent endometrial cancer."

The B2 cohort of the Phase 1/2 RAINFOL-01 study (NCT05579366) is a dose expansion cohort evaluating the efficacy and safety of Rina-S in patients with advanced or recurrent endometrial cancer. In the study, 64 patients with heavily pretreated advanced or recurrent endometrial cancer whose disease had progressed on or after an anti-PD-(L)1 and platinum-based chemotherapy were enrolled and treated with Rina-S. Patients were administered either 100 mg/m2 (n=22) or 120 mg/m2 (n=42) of Rina-S. In the 100 mg/m2 cohort, the confirmed ORR was 50.0 percent, including two CRs. Anti-tumor activity was also observed in patients treated with Rina-S 120 mg/m2 Q3W, which resulted in 47.1 percent confirmed ORR. The mDoR was not reached after a median follow-up of 7.7 months in the 100 mg/m2 cohort and a median follow-up of 9.8 months in the 120 mg/m2 cohort. Median age was 67.0 years and 69.5 years in the 100 mg/m2 and 120 mg/m2 cohorts, respectively. Study participants were previously treated with a median of three lines of therapy (range 1-8).

Common treatment emergent adverse events (TEAEs; all grades) included diarrhea, shortness of breath (dyspnea), urinary tract infection, headache, constipation, decreased appetite, vomiting, fatigue and nausea. Serious TEAEs (Grade 3 or higher) occurred in 31.8 percent and 50.0 percent of patients treated with Rina-S 100 mg/m2 and 120 mg/m2, respectively. Hematologic adverse events were manageable without significant dose reduction and with low rates of treatment discontinuation. No signals of ocular toxicities, neuropathy or Interstitial Lung Disease (ILD) were observed. Ocular toxicities and ILD are often reported as adverse events associated with ADCs i,ii,iii,iv.

"Rina-S represents the kind of innovation that defines our focus at Genmab, which is to develop wholly owned, novel antibody-based medicines that have the potential to transform the treatment of cancer and address an unmet need, including for patients with advanced endometrial cancer," said Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer of Genmab. "The encouraging early signals in endometrial cancer underscore our deep commitment to making a meaningful impact for women with gynecologic cancers, where treatment advances have long lagged behind the need."

About the RAINFOLTM -01 Trial
RAINFOL-01 (NCT05579366) is an open-label, multicenter Phase 1/2 study, designed to evaluate the safety and efficacy of rinatabart sesutecan (Rina-S) Q3W at various doses in solid tumors that are known to express FRα. The study consists of multiple parts including Part A monotherapy cohorts; Part B tumor-specific monotherapy dose-expansion cohorts; Part C platinum-resistant ovarian cancer (PROC) cohort; Part D combination therapy cohorts; and Part F a monotherapy endometrial cancer (EC) cohort.

About Endometrial Cancer
Endometrial cancer (EC) ranks as the second most prevalent gynecologic cancer globally, with increasing incidence and mortality ratesv,vi, highlighting the need for effective management strategies. Patients with advanced or recurrent EC have a relatively poor prognosis and treatment options are limited for those patients who have progressed following treatment with chemotherapy and immune checkpoint inhibitor. FRα is overexpressed on multiple tumors, including EC, making it a promising therapeutic target. Anti-tumor activity with Rina-S was observed across a broad range of FRα expression, and there are currently no approved FRα-targeting therapies approved for the treatment of endometrial cancer.

EC starts in the lining of the uterus, known as the endometrium.vii Patients with advanced or recurrent endometrial cancer have a high unmet need. Most (64-74 percent) patients with EC experience disease progression on immune checkpoint inhibitors (ICI) plus chemotherapy irrespective of biomarker status. Treatment options after progression on an ICI-regimen are very limited and consist of single-agent chemotherapy (ORR <16 percent and median progression-free survival [PFS] <5 months).

About Rinatabart Sesutecan (Rina-S; GEN1184)
Rinatabart sesutecan (Rina-S; GEN1184) is an investigational ADC. It is composed of a novel human monoclonal antibody directed at folate receptor α (FRα), a novel hydrophilic protease-cleavable linker, and exatecan, a topoisomerase I inhibitor payload. The clinical trial program for Rina-S continues to expand including ovarian, endometrial and other cancers of unmet need. In January 2024, the U.S. Food and Drug Administration granted Fast Track designation to Rina-S for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

Rina-S is advancing through late-stage development, supported by a growing portfolio of Phase 2 and Phase 3 trials, including further evaluation of single-agent Rina-S in patients with advanced endometrial cancer in Part F of the ongoing RAINFOL-01 trial and in a planned Phase 3 trial.

The safety and efficacy of rinatabart sesutecan has not been established. Please visit www.clinicaltrials.gov for more information.

On June 2, 2025 Enterome SA, a clinical-stage company developing first-in-class OncoMimics immunotherapies to treat cancer, reported it will present positive data from its Phase 1/2 clinical study with EO2463, its lead clinical program, as monotherapy and in combination with lenalidomide and/or rituximab to treat indolent Non-Hodgkin lymphoma (iNHL) at the International Conference on Malignant Lymphoma (ICML) in Lugano on June 21, 2025 (Press release, Enterome, JUN 2, 2025, View Source [SID1234653605]).

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As indicated by the data generated by Enterome’s ongoing SIDNEY study, EO2463 has the potential to become a frontline therapy in iNHL, either as monotherapy or in combination regimens, across all patient groups suffering from the disease, including in watch-and-wait settings, first-line therapy, and in relapsed/refractory settings.

The title of the peer-reviewed presentation is "EO2463 (EO) peptide immunotherapy in combination with lenalidomide (L) and rituximab (R) in patients (pts) with follicular (FL) and marginal zone lymphoma (MZL)", and will be presented by Dr Jose Caetano (JC) Villasboas Bisneto, principal study investigator at the Mayo Clinic in Rochester, MN, USA.

"We look forward to sharing these interim Phase 2 data, which suggest to us that our lead OncoMimics immunotherapeutic candidate EO2463 could have broad potential to benefit patients suffering from multiple clinical presentations of Follicular Lymphoma. Later this month, Dr Villasboas will present interim data obtained more specifically in iNHL patients with relapsed/refractory disease," said Pierre Bélichard, Chief Executive Officer of Enterome.

"Just this past weekend we presented positive Phase 1/2 data from the AUDREY trial in metastatic colorectal cancer with our second-most advanced OncoMimics immunotherapeutic candidate, EO4010, at ASCO (Free ASCO Whitepaper). OncoMimics represent a new therapeutic modality that has tremendous potential for cancer treatment."

Separately, Enterome recently held a positive Type-C meeting with the FDA, outlining a clear regulatory path to marketing approval for EO2463 in iNHL after constructive discussion with the regulator.

In addition, this week, Enterome will participate at the Jefferies Global Healthcare Conference in New York ( June 3 to 5). Pierre Bélichard and Chief Financial Officer Christelle Dumoussaud will meet with investors and industry partners during the event.

SIDNEY is a 12-month open label study that aims to assess safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in some 48 patients with follicular lymphoma and marginal zone lymphoma. The study is comprised of four cohorts: 1) relapsed/refractory iNHL patients, who received EO2463 monotherapy for 6 weeks, followed by combination with lenalidomide plus rituximab for 16 weeks; 2) EO2463 monotherapy in newly diagnosed untreated stage III/IV iNHL classified as "watch and wait"; 3) EO2463 monotherapy followed by combination with rituximab in newly diagnosed previously untreated stage III/IV iNHL patients classified with low tumor burden in need of therapy; 4) relapsed/refractory iNHL patients, having received at least one prior treatment. EO2463 and lenalidomide are given in combination from treatment inception with addition of rituximab at week 19.

Enterome has previously presented interim data from the study at major international conferences held by the European Hematology Association (EHA) (Free EHA Whitepaper), the American Society of Hematology (ASH) (Free ASH Whitepaper), and the American Society for Cancer and Oncology.

EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimic peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2).

The unique ability of EO2463 immunotherapy to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes. By ensuring broad target coverage across malignant B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune-resistance mechanisms such as antigen escape.

On June 2, 2025 Eli Lilly and Company (NYSE: LLY) reported new Phase 1 data showing that its folate receptor alpha (FRα) antibody-drug conjugate (ADC) (LY4170156) demonstrated an encouraging safety profile and anti-tumor activity across dose and FRα expression levels in women with heavily pre-treated platinum-resistant ovarian cancer, including patients previously treated with mirvetuximab soravtansine (Press release, Eli Lilly, JUN 2, 2025, View Source [SID1234653604]). A preliminary overall objective response rate (ORR) of 55% was observed at the potential recommended Phase 2 dose of 4 mg/kg. Lilly’s FRα targeting ADC is composed of an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker. These data will be presented today in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"ADCs have begun to change the treatment paradigm for some women with ovarian cancer, but a large proportion of patients still have a significant need for new therapies that improve outcomes regardless of FRα expression level," said Isabelle Ray-Coquard, M.D., Ph.D., president of the ENGOT (European Network of Gynecological Oncology Trial) group, medical oncologist at the Centre Léon Bérard Lyon France and principal investigator for the trial. "These initial data show activity across all doses and levels of FRα expression, including in patients previously treated with a FRα targeting treatment. Taken together with the emerging safety and tolerability profile, these data demonstrate early potential to meaningfully improve outcomes for women living with advanced ovarian cancer."

As of the March 9, 2025 data cutoff, the study enrolled 95 participants with high-grade serous ovarian cancer across four dose levels (2 – 6 mg/kg). Patients received a median of five prior systemic regimens (range 1-10), and 15% were previously treated with mirvetuximab soravtansine. Among the 95 patients, 51% had tumors with FRα expression less than 75%, 34% had FRα expression of 75% or higher, and 16% had expression results pending. Key endpoints were safety, pharmacokinetics, and anti-tumor activity per RECIST v1.1.

Efficacy results demonstrate responses at all dose levels, across all FRα expression levels, including in patients who progressed on prior mirvetuximab soravtansine. In the 58 efficacy-evaluable patients (37 patients remain ongoing prior to first response assessment and were therefore not yet efficacy-evaluable at the time of the data cutoff), the ORR was 45% (26/58 patients), and the disease control rate was 74% (43/58). At the potential recommended Phase 2 dose of 4 mg/kg, the ORR was 55% (11/20 patients). The most common treatment-emergent adverse events across all dose levels included nausea (64%), anemia (40%), fatigue (32%), vomiting (32%), diarrhea (28%), and neutropenia (27%). Treatment-emergent neuropathy and ocular toxicity has not been observed to date. No maximum tolerated dose has been established.

"We are excited to share these first clinical data for our FRα targeting ADC, demonstrating a promising tolerability and efficacy profile across all FRα expression levels," said David Hyman, M.D., Chief Medical Officer, Lilly. "Based on these results, we believe there is the potential to significantly expand the number of ovarian cancer patients who could benefit from a FRα ADC. We are now focused on rapidly advancing this potential new medicine into registrational Phase 3 clinical trials."

For more information on Lilly’s oncology pipeline click here.

About LY4170156
LY4170156 is an investigational, next-generation antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα). FRα is a cell-surface glycoprotein encoded by the gene FOLR1 that binds to the essential nutrients folic acid and reduced folates, bringing them into cells to facilitate cell division and growth.1,2 FRα is overexpressed in many solid tumors such as ovarian, non-small cell lung, and colorectal cancers.1,3,4

LY4170156 was designed to target FRα across expression levels with an improved therapeutic index. LY4170156 is composed of an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker (PSARlink). PSARlink’s unique structure "masks" the cytotoxic molecules enabling them to stay in the body longer, providing the potential to broaden the therapeutic index of ADCs. LY4170156 is currently being studied in patients with ovarian cancer as well as other FRα-expressing solid tumors, NCT06400472.

On June 2, 2025 Eli Lilly and Company (NYSE:LLY) reported it will participate in the Goldman Sachs 46th Annual Global Health Care Conference on June 10, 2025. Lucas Montarce, Lilly executive vice president and chief financial officer, will take part in a fireside chat at 8 a.m., Eastern time (Press release, Eli Lilly, JUN 2, 2025, View Source [SID1234653603]).

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A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.

On June 2, 2025 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, reported data from its pivotal Phase 3 ROSELLA trial of relacorilant plus nab-paclitaxel in patients with platinum-resistant ovarian cancer in a late-breaking oral presentation at the ASCO (Free ASCO Whitepaper) 2025 (American Society of Clinical Oncology) Annual Meeting (Press release, Corcept Therapeutics, JUN 2, 2025, https://ir.corcept.com/news-releases/news-release-details/corcept-presents-pivotal-clinical-data-asco-late-breaker [SID1234653602]).

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The presentation abstract can be found here and the presentation slides here. The data have been simultaneously published in The Lancet, titled "Relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): an open-label, randomised, controlled, phase 3 trial."

ROSELLA met its primary endpoint of improved progression-free survival as assessed by blinded independent central review (PFS-BICR). Patients who received relacorilant in addition to nab-paclitaxel chemotherapy experienced a 30 percent reduction in risk of disease progression compared to patients who received nab-paclitaxel monotherapy (hazard ratio: 0.70; p-value: 0.0076). Median PFS-BICR was extended to 6.5 months, compared to 5.5 months in patients who received nab-paclitaxel alone. In addition, PFS assessed by investigators was consistent with PFS-BICR, with a hazard ratio of 0.71 (p-value: 0.0030). An interim analysis of overall survival (OS), showed that the addition of relacorilant reduced the risk of death by 31 percent, substantially lengthening patients’ lives. Median OS for patients who received relacorilant was 16.0 months, compared to 11.5 months for patients who received nab-paclitaxel alone (hazard ratio: 0.69; p-value: 0.0121). These benefits were seen in all clinically relevant subgroups, including those with poor prognoses.

Relacorilant plus nab-paclitaxel was well-tolerated, with a comparable safety profile between treatment arms. The addition of relacorilant did not increase patients’ safety burden. In addition, patients treated with relacorilant plus nab-paclitaxel had a lower incidence of ascites (5.3 percent), than did patients who received nab-paclitaxel alone (10.5 percent). The occurrence of abdominal paracenteses during treatment was also lower for patients treated with relacorilant plus nab-paclitaxel (7.4 percent), compared to nab-paclitaxel alone (13.2 percent).

"For many patients with advanced, recurrent ovarian cancer, the tumor eventually becomes resistant to chemotherapy, and oncologists have few good treatment options. Relacorilant plus nab-paclitaxel may provide a powerful tool for improving progression-free and overall survival in patients with this disease," said Alexander B. Olawaiye, M.D., Director of gynecological cancer research at Magee-Women’s Hospital of the University of Pittsburgh and Principal Investigator in the ROSELLA trial. "The data presented at ASCO (Free ASCO Whitepaper) 2025 and published in The Lancet support this regimen becoming a new standard-of-care treatment."

"These data show that treatment with relacorilant can help patients with platinum-resistant ovarian cancer live longer, without adding to their safety burden. We plan to bring this treatment option to patients as quickly as possible and are working on our regulatory applications in the U.S. and Europe. We want to thank all the patients and investigators who participated in this trial," said Bill Guyer, PharmD, Corcept’s Chief Development Officer. "These data also illustrate the benefits of modulating cortisol activity in patients whose tumors express the glucocorticoid receptor. We have initiated a trial evaluating the benefit of adding relacorilant to a regimen of nab-paclitaxel and bevacizumab (BELLA Trial), and are considering additional clinical trials."

ROSELLA enrolled 381 patients with platinum-resistant ovarian cancer at sites in the United States, Europe, South Korea, Brazil, Argentina, Canada and Australia; biomarker selection was not required. Patients were randomized 1:1 to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone. ROSELLA has dual primary endpoints — PFS-BICR and OS. A positive outcome is achieved if either endpoint is met.

The ROSELLA trial is being conducted in collaboration with The GOG Foundation, Inc. (GOG-F), the European Network of Gynaecological Oncological Trial groups (ENGOT), the Asia-Pacific Gynecologic Oncology Trials Group (APGOT), the Latin American Cooperative Oncology Group (LACOG), and the Australia New Zealand Gynaecological Oncology Group (ANZGOG).

About Relacorilant

Relacorilant, an oral therapy, is a selective glucocorticoid receptor (GR) antagonist that modulates cortisol activity by binding to the GR but not to the body’s other hormone receptors. Corcept is studying relacorilant in a variety of serious disorders in addition to ovarian cancer, including endogenous hypercortisolism (Cushing’s syndrome) and prostate cancer. Relacorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents. It has been designated an orphan drug by the FDA and the European Commission (EC) for the treatment of hypercortisolism and by the EC for the treatment of ovarian cancer.

About Platinum-Resistant Ovarian Cancer

Ovarian cancer is the fifth most common cause of cancer death in women. Patients whose disease returns less than six months after receiving platinum-containing therapy have "platinum-resistant" disease. There are few treatment options for these women. Median overall survival following recurrence is approximately 12 months with single-agent chemotherapy. Approximately 20,000 women with platinum-resistant disease are candidates to start a new therapy each year in the United States, with at least an equal number in Europe.