On October 19, 2025 SystImmune Inc. (SystImmune), a clinical-stage biotechnology company, reported positive topline results from the BL-B01D1-301 trial. The trial has met one of the dual primary endpoints (BICR-assessed ORR) as iza-bren has demonstrated a statistically significant and clinically meaningful improvement in BICR-assessed ORR in recurrent or metastatic NPC patients who had progressed after at least two prior lines of chemotherapy, including platinum-based chemotherapy and a PD-1/PD-L1 inhibitor. These results were presented today in a late-breaking oral presentation at the 2025 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

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Iza-bren is a potentially first-in-class topoisomerase 1 inhibitor-based bispecific antibody-drug conjugate (ADC) which targets both epidermal growth factor receptor and human epidermal growth factor receptor 3 (EGFRxHER3). It is being developed by Biokin in China and jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement in territories outside of China.

Iza-bren has shown a BICR-assessed ORR of 54.6% vs. 27.0% (Odds Ratio 3.3; 95% confidence interval 1.9-5.8; p<0.0001). Median duration of response (DoR) was 8.5 months for iza-bren versus 4.8 months for physician’s choice of chemotherapy (Hazard ratio 0.43; 95% CI 0.22 to 0.83). Furthermore, median progression-free survival (PFS) was 8.38 months with iza-bren compared to 4.34 months for chemotherapy (hazard ratio of 0.44; 95% confidence interval 0.32-0.62). The ORR and PFS benefits were consistent across all subgroup analysis. At the time of this analysis, the overall survival (OS) data were immature.

Iza-bren was well-tolerated with a manageable safety profile. The most common adverse events were hematological toxicities, which were effectively managed with standard supportive care. Two patients in the iza-bren arm experienced Grade 2 interstitial lung disease (ILD), whereas two patients in the chemotherapy arm experienced Grade 3 ILD. The safety profile in the BL-B01D1-303 study was consistent with the known profiles of the therapy with no new safety signals identified.

"The positive topline results from the first registrational trial of iza-bren presented at ESMO (Free ESMO Whitepaper) demonstrated clear clinical benefits of iza-bren compared to traditional chemotherapy. These data add to the growing body of clinical evidence that continues to reinforce our confidence in iza-bren’s mechanism of action and therapeutic potential. We believe iza-bren can deliver clinically meaningful benefit by targeting key cancer biological pathways to improve outcomes for patients across a broad range of advanced malignancies," added Dr. Jonathan Cheng, Chief Medical Officer of SystImmune.

The New Drug Application (NDA) for iza-bren for the treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC) has been submitted by Biokin to the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) in China.

About BL-B01D1-303

BL-B01D1-303 is a phase III, randomized, open-label, multicenter study in China to evaluate the efficacy and safety of BL-B01D1 in patients with recurrent or metastatic nasopharyngeal carcinoma who have failed PD-1/PD-L1 monoclonal antibody and at least two lines chemotherapy (one line must contain platinum-based chemotherapy). For more detailed information, please visit clinical.trials.gov (NCT06118333).

About Nasopharyngeal Carcinoma (NPC)

Nasopharyngeal Carcinoma (NPC) is a type of head and neck cancer that originates in the nose. NPC is uncommon globally, but is endemic in southern China, southeast Asia and parts of Africa, and is rising among the immigrant population in US and Europe. NPC is strongly associated with EBV infection. There is a significant unmet need as 5-year overall survival rate is generally less than 10% in the later line metastatic setting.

About iza-bren

SystImmune, in collaboration with BMS outside of China, is developing iza-bren (BL-B01D1), a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3, which are highly expressed in various epithelial cancers and are known to be associated with cancer cell proliferation and survival. Iza-bren’s dual mechanism of action blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. In addition, upon antibody mediated internalization, iza-bren’s therapeutic novel Topo1i payload is released causing cytotoxic stress that leads to cancer cell death.

(Press release, SystImmune, OCT 19, 2025, View Source [SID1234656797])

On October 19, 2025 Gilead Sciences, Inc. (Nasdaq: GILD) reported positive data from the Phase 3 ASCENT-03 study demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) for Trodelvy (sacituzumab govitecan-hziy) compared to chemotherapy as first-line treatment in patients with metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitors. These findings will be presented today during a late-breaking oral session at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Abstract #LBA20) and simultaneously published in The New England Journal of Medicine.

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ASCENT-03 successfully met its primary endpoint of PFS with a 38% reduced risk of disease progression or death for Trodelvy versus chemotherapy (HR: 0.62; p<0.0001). Median PFS with Trodelvy was 9.7 months versus 6.9 months for chemotherapy. The PFS results for Trodelvy versus chemotherapy were consistent across prespecified subgroups, including among patients with poorer prognosis (such as those whose cancer recurred less than one year after treatment in the curative setting) and regardless of chemotherapy chosen.

"Patients with metastatic TNBC who are ineligible for immunotherapy face an especially poor prognosis, with limited treatment options and fast disease progression," said Dr. Javier Cortés, Head of the International Breast Cancer Center in Spain and principal investigator of the ASCENT-03 study. "The ability of sacituzumab govitecan to significantly delay death and progression could represent the first major treatment advance for this patient population in the 20 years since TNBC was defined, marking an historic shift and establishing a potential new standard of care."

The objective response rate (ORR) was 48% with Trodelvy and 46% with chemotherapy. Median duration of response (DOR) was substantially longer with Trodelvy. Among patients with confirmed complete or partial responses, DOR for Trodelvy was 12.2 months compared to 7.2 months with chemotherapy.

Overall survival (OS) data were not mature at the time of PFS primary analysis. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analysis planned.

These results complement the recent presentation of ASCENT-04/KEYNOTE-D19, which showed a significant PFS benefit for Trodelvy plus Keytruda (pembrolizumab) in PD-L1+ first-line metastatic TNBC. Gilead is engaging with the U.S. Food and Drug Administration and other global regulators regarding both data sets.

"ASCENT-03 is the second Phase 3 trial with a Trodelvy-based regimen to show superior progression-free survival over chemotherapy in first-line metastatic TNBC, highlighting its potential to improve outcomes for patients with limited treatment options," said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. "With these potentially practice-changing results, Trodelvy is poised to transform the first-line metastatic TNBC treatment landscape, offering a much-needed alternative to chemotherapy."

Summary of Key ASCENT-03 Results

Efficacy: Intent-to-Treat Population

Trodelvy (n=279)

Chemotherapy (n=279)

Median PFS

9.7 months (95% CI: 8.1-11.1)

6.9 months (95% CI: 5.6-8.2)

PFS hazard ratio and p-value

0.62 (95% CI: 0.50-0.77); p<0.0001

ORR

48% (95% CI: 42-54)

46% (95% CI: 40-52)

DOR

12.2 months (95% CI: 9.7-13.8)

7.2 months (95% CI: 5.7-8.4)

The safety profile of Trodelvy in the ASCENT-03 study was consistent with prior studies, and no new safety signals were identified in this patient population. The most frequent grade ≥3 treatment-emergent adverse events were neutropenia (43%) and diarrhea (9%) with Trodelvy and neutropenia (41%) and anemia (16%) with chemotherapy. Fewer patients discontinued treatment due to adverse events on Trodelvy than with chemotherapy (4% vs. 12%).

Healthcare professionals have well-established experience with Trodelvy, with more than 60,000 breast cancer patients treated across 50+ countries over the past five years. It remains the only Trop-2-directed antibody-drug conjugate (ADC) to demonstrate meaningful survival benefits in both 2L+ metastatic TNBC and pre-treated HR+/HER2- metastatic breast cancer. It is also the only ADC with four positive Phase 3 trials in HER2- mBC (IHC 0, IHC 1+, or IHC 2+/ISH–).

The use of Trodelvy plus Keytruda in patients with first-line PD-L1+ metastatic TNBC and Trodelvy as monotherapy in patients with first-line metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitors are investigational, and the safety and efficacy of these uses have not been established.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Triple-Negative Breast Cancer (In Patients Who Are Not Candidates for PD-1/PD-L1 inhibitors)

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC disproportionately impacts younger, pre-menopausal as well as Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of metastatic breast cancer.

Chemotherapy remains the mainstay of treatment in first-line metastatic TNBC patients who are not candidates for PD-1/PD-L1 inhibitors, and the need to improve outcomes continues to be high as there has not been a clinically meaningful advance for this patient population in over 20 years. In metastatic TNBC overall, ~50% of patients do not receive treatment beyond the first-line setting, demonstrating a need for additional effective earlier-line treatment options.

About the ASCENT-03 Study

The ASCENT-03 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of Trodelvy compared with treatment of physician’s choice in patients with previously untreated, locally advanced, inoperable, or metastatic triple-negative breast cancer whose tumors do not express PD-L1, or who are PD-L1 positive and previously treated with a PD-(L)1 inhibitor in the curative setting. 558 patients were enrolled across multiple study sites worldwide.

Patients were randomized 1:1 to receive either Trodelvy (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) or treatment of physician’s choice, which included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. Patients randomized to chemotherapy were eligible to cross over to Trodelvy upon disease progression.

The primary endpoint of the study is progression-free survival (PFS) as assessed by BICR according to RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs) and safety.

More information about ASCENT-03 is available at ClinicalTrials.gov: NCT05382299.

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer.

(Press release, Gilead Sciences, OCT 19, 2025, View Source [SID1234656782])

Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer—including in curative settings—as well as in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.

INDICATIONS

TRODELVY (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
IMPORTANT SAFETY INFORMATION

BOXED WARNING: NEUTROPENIA AND DIARRHEA

TRODELVY can cause severe, life-threatening, or fatal neutropenia. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Primary prophylaxis with G-CSF is recommended for all patients at increased risk of febrile neutropenia. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
TRODELVY can cause severe diarrhea. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to TRODELVY.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur as early as the first cycle of treatment and may require dose modification. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm3 on Day 1 of any cycle or below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 of USPI.

Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤ Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions.

Nausea and Vomiting: TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

ADVERSE REACTIONS

In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY.

UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY.

Please see full Prescribing Information, including BOXED WARNING.

On October 19, 2025 Multitude Therapeutics, Inc., a clinical stage biopharmaceutical company focused on the development of ADC drugs, reported interim results from its ongoing Phase I/II open-label, multicenter dose escalation and expansion study evaluating AMT-253, a MUC18-directed antibody-drug-conjugate (ADC), in patients with melanoma and other advanced solid tumors. The data are being presented on October 19th at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting being held in Berlin, Germany.

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Phase I/II clinical trials are ongoing in both Australia and China. This first-in-human study will evaluate the Maximum Tolerated Dose (MTD) / the Recommended Phase II Dose (RP2D), safety, tolerability, anti-tumor activity, pharmacokinetics, pharmacodynamics and immunogenicity of AMT-253, in patients with advanced solid tumors. The Phase Ia portion will determine the recommended doses for expansion, and the Phase Ib/II portion will focus on further characterizing safety and efficacy in select tumor types.

As of September 8th, 2025, safety data are available for 170 patients who have received AMT-253 once every three weeks (Q3W) at doses ranging from 1.6 to 5.6 mg/kg. Primary tumor types are melanoma, endometrial cancer, cervical squamous cancer and uterine leiomyosarcoma. In heavily pretreated melanoma patients, with prior lines of therapy ranging from 1-7, promising efficacy was observed without MUC18 preselection. The overall response rate (ORR) was 28.6% in all melanomas (16/56, 15 confirmed, 1 unconfirmed still on-treatment) across all dose levels. In melanoma patients without prior chemotherapy, ORR was 35% (7/20, all confirmed), 50% (5/10; 4 confirmed, 1 unconfirmed still on-treatment), and 33.3% (1/3, confirmed) for the cutaneous, acral, and mucosal subtypes, respectively; preliminary mPFS was 8.6, 8.3, and 11.0 months. Among 18 cutaneous melanoma patients at the potential expansion doses, ORR was 38.9% (7/18, all confirmed), and preliminary mPFS was 8.6 months. Preliminary antitumor activity was also observed in endometrial cancer, cervical squamous carcinoma and uterine leiomyosarcoma patients. Responses were observed across MUC18 expression levels in all tumor patients evaluated. AMT-253 showed a safety profile consistent with other topoisomerase-1 (TOP1) inhibitor–based ADCs, with manageable hematologic toxicities as the most common treatment-related adverse events. No treatment-related cases of neuropathy or pneumonitis were observed as of the data cutoff.

"We are excited by the durable antitumor activity observed in the early clinical results of AMT-253, particularly in unselected, late-line metastatic melanoma patients, where the unmet medical need remains high," said Dr. Shu-Hui Liu, Co-founder and CSO of Multitude Therapeutics. "These initial data, together with our previously published preclinical findings*, highlight the potential of AMT-253 to offer meaningful outcome improvement to patients who have exhausted standard-of-care options. We look forward to further clinical confirmation of these results and to fully exploring the potential of this novel ADC for greater patient benefit."

*Shi et al., (2023) Cancer Research 83:3783-95

Poster Presentation Details:

Title: Ongoing Phase I trial results of AMT-253, a first-in-class MUC18-targeting antibody-drug conjugate in patients with melanoma and other advanced solid tumors
Session Title: Developmental therapeutics
Date and Time: October 19th – 09:00-17:00
Poster Number: 997P
Location: Hall 25, Level 2

About AMT-253

AMT-253, a MUC18 ADC, is composed of a proprietary antibody with high MUC18 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is designed to complement the exatecan payload, enabling a stable and homogenous ADC. The payload is a weak substrate for BCRP/P-gp, which are drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, this linker-payload has been shown to have an increased "bystander effect" compared to the equivalent of competitor ADCs**. AMT-253 has a drug-to-antibody ratio of eight. AMT-253 is being evaluated in a Phase I/II study in patients with melanoma and other advanced solid tumors. Additional information on the AUS PhI(NCT05906862) and China PhI/II (NCT06209580) trials can be found at clinicaltrials.gov.

(Press release, Multitude Therapeutics, OCT 19, 2025, View Source [SID1234656798])

On October 19, 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 new late-breaking data from its pivotal Phase 3 ROSELLA trial of relacorilant plus nab-paclitaxel in patients with platinum-resistant ovarian cancer at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2025 Annual Meeting. The data demonstrated a progression-free survival (PFS) benefit for patients who experienced disease progression while on or after taking a PARP inhibitor (PARPi), a patient population with particularly poor prognosis. The presentation slides can be found here. The company also announced expansion of the Phase 2 BELLA trial in a poster session at ESMO (Free ESMO Whitepaper), found here.

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New relacorilant data presented at ESMO (Free ESMO Whitepaper) demonstrated a consistent benefit in PARPi subgroups to overcome chemotherapy resistance. Relacorilant plus nab-paclitaxel showed a PFS benefit in patients with prior PARPi treatment (hazard ratio: 0.60; p-value: 0.0035) and in patients whose disease progressed while on a PARPi (hazard ratio: 0.56; p-value: 0.0046), with a median PFS of 7.36 months for both subgroups. Relacorilant plus nab-paclitaxel was well-tolerated in the PARPi subgroups, consistent with its known safety profile. Importantly, the type, frequency and severity of adverse events in the combination arms were comparable to those in the nab-paclitaxel monotherapy arms. Relacorilant conferred its benefit without increasing the safety burden of the patients who received it.

"These new ROSELLA data substantiate the significant benefit of relacorilant plus nab-paclitaxel in platinum-resistant ovarian cancer, an extremely difficult-to-treat cancer," said Domenica Lorusso, M.D., Ph.D., Director of the Gynaecological Oncology Unit at Humanitas Hospital San Pio X, Milan, and Full Professor of Obstetrics and Gynaecology, Humanitas University, Rozzano, European Network of Gynaecological Oncological Trial groups Principal Investigator in the ROSELLA trial and ESMO (Free ESMO Whitepaper) presenter. "These findings are especially promising for patients with an exceptionally poor prognosis and necessitate further research of relacorilant and its potential benefit in earlier treatment lines of gynecological cancers."

Corcept also announced the expansion of the recently initiated Phase 2 BELLA trial to three study arms to evaluate the efficacy and safety of: (i) relacorilant plus nab-paclitaxel and bevacizumab to treat patients with platinum-resistant ovarian cancer; (ii) relacorilant plus nab-paclitaxel and bevacizumab to treat patients with platinum-sensitive ovarian cancer whose disease progressed while on a PARPi and (iii) relacorilant plus nab-paclitaxel to treat patients with endometrial cancer who had received one or two prior lines of therapy. Initial results are expected in late 2026.

"The ROSELLA data give us confidence to expand the BELLA trial to include patients with ovarian cancer whose disease is platinum sensitive (an earlier stage of tumor progression), as well as patients with endometrial cancer," said Bill Guyer, PharmD, Corcept’s Chief Development Officer. "With the FDA’s recent acceptance of our New Drug Application for relacorilant in platinum-resistant ovarian cancer and the expansion of our BELLA trial, we are closer than ever to bringing new and vital treatment to patients in need. We are grateful to all the patients and investigators for participating in our ongoing trials."

Corcept previously announced that ROSELLA met its primary endpoint of improved PFS, with no need for biomarker selection. Patients who received relacorilant in addition to nab-paclitaxel chemotherapy experienced a 30 percent reduction in the risk of disease progression compared to patients who received nab-paclitaxel monotherapy (hazard ratio: 0.70; p-value: 0.0076). 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 (hazard ratio: 0.69; p-value: 0.0121).

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 developing relacorilant in ovarian cancer and a variety of other serious disorders, including endogenous hypercortisolism 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. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of December 30, 2025 for relacorilant as a treatment for patients with hypercortisolism, and a PDUFA date of July 11, 2026 for relacorilant as a treatment for patients with platinum-resistant ovarian cancer. Corcept also recently submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for relacorilant to treat patients with platinum-resistant ovarian cancer.

About Cortisol’s Role in Oncology

Cortisol plays a role in tumor growth through several mechanisms. It helps solid tumors resist chemotherapy by inhibiting cellular apoptosis — the tumor-killing effect chemotherapy is meant to stimulate. In some cancers, cortisol promotes tumor growth by activating oncogenes in the cells to which it binds. Cortisol also suppresses the body’s immune response, which weakens its ability to fight all diseases, including cancer.

About Ovarian Cancer

Ovarian cancer is the fifth most common cause of cancer death in women. Patients whose disease returns six months after receiving platinum-containing therapy have "platinum-sensitive" disease and those with disease progression of less than six months have "platinum-resistant" disease. There are few treatment options for these women. Approximately 20,000 women with platinum-resistant disease and 13,000 women with platinum-sensitive disease are candidates to start a new therapy each year in the United States, with at least an equal number in Europe.

(Press release, Corcept Therapeutics, OCT 19, 2025, https://ir.corcept.com/news-releases/news-release-details/corcept-presents-esmo-2025-late-breaker-relacorilant [SID1234656765])

On October 19, 2025 Carsgen therapeutcis reported primary plasma cell leukemia (pPCL) is a rare and highly aggressive plasma cell malignancy, often associated with complex genetic abnormalities. There is currently no standard treatment regimens, and conventional therapies for multiple myeloma are typically used. While targeted agents and autologous hematopoietic stem cell transplantation can slightly extend the overall survival of pPCL patients to 1.5–3 years, relapsed/refractory pPCL after multiple lines of therapy presents a significant clinical challenge due to the extremely limited treatment options and rapid disease progression, making it difficult to re-induce remission with existing therapies.

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CT0596 is an allogeneic BCMA-targeted CAR-T therapy developed using CARsgen’s proprietary THANK-u Plus platform. It is currently being evaluated in investigator-initiated trials for plasma cell malignancy. As of the data cutoff date (Oct 17, 2025), two patients with relapsed/refractory pPCL had been enrolled. Details are as follows:

pPCL-01:

A 62-year-old male with IgG-λ type experienced poor disease control and rapid progression despite previous autologous hematopoietic stem cell transplantation and treatment with triple classes of drugs (proteasome inhibitor, immunomodulatory agent, and CD38 monoclonal antibody). By the screening period, his serum free light chain level had reached 10,374.86 mg/L. The patient underwent two CAR-T cell infusions approximately two months apart: he first received low-dose lymphodepletion and a relatively lower dose of CAR-T cells per protocol, then followed one cycle of bridge therapy. About one month after the failure of bridge therapy, he received a second CAR-T cell infusion. Following this infusion, he developed Grade 2 CRS, Grade 4 cytopenia, and a lung infection, but recovered after supportive treatment including tocilizumab, corticosteroids, autologous stem cell infusion, and anti-infective therapy. CAR-T cells expanded robustly, with a peak copy number (Cmax) of 161,971 copies/μg gDNA, and copy numbers remained at 10³ by Week 8. Efficacy assessments at both Week 4 and Week 8 post-infusion showed stringent complete response (sCR), and bone marrow minimal residual disease (MRD) was negative (< 10⁻⁶) at Week 4.

pPCL-02:

A 70-year-old male with κ light chain had previously been treated with triple classes of drugs (proteasome inhibitor, immunomodulatory agent, and CD38 monoclonal antibody). The patient developed Grade 1 CRS, Grade 4 neutropenia, and thrombocytopenia following lymphodepletion and CAR-T cell infusion. The CRS and cytopenias were resolved after treatment with tocilizumab and other supportive measures. CAR-T cells expanded robustly, with a Cmax of 151,654 copies/μg gDNA. The patient achieved sCR at the Week 4, Week 8, and Week 12 assessments post-infusion, with bone marrow MRD negative (< 10⁻⁶) at both Week 4 and Week 12.

Based on the current findings, CT0596 has exhibited robust and rapid efficacy in heavily pretreated patients with rapidly progressive relapsed/refractory pPCL. Both pPCL patients achieved sCR following CT0596 infusion, with peak CAR-T cell copy numbers exceeding 10⁵ copies/μg gDNA. Aside from expected CAR-T-associated toxicities such as CRS and hematologic adverse events, no significant organ toxicities were observed, indicating a manageable safety profile. These results lend strong support to the continued investigation of CT0596 across a broader spectrum of plasma cell neoplasms.

About CT0596

CT0596 is an allogeneic BCMA-targeted CAR-T therapy developed using CARsgen’s proprietary THANK-u Plus platform. It is currently being evaluated in investigator-initiated trials for relapsed/refractory multiple myeloma (R/R MM) or plasma cell leukemia (PCL). CT0596 demonstrated preliminary favorable tolerability and encouraging efficacy signals. Further investigation is planned in additional plasma cell malignancies and autoimmune diseases mediated by autoreactive plasma cells. The company anticipates submitting an Investigational New Drug (IND) application in the second half of 2025.

(Press release, Carsgen Therapeutics, OCT 19, 2025, View Source;preliminary-clinical-data-of-carsgens-allogeneic-bcma-car-t-product-ct0596-for-the-treatment-of-primary-plasma-cell-leukemia-302588331.html [SID1234656799])