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])

On October 19, 2025 Taiho Pharmaceutical Co., Ltd. ("Taiho") and Arcus Biosciences, Inc. (NYSE:RCUS, "Arcus") reported that Taiho exercised its option to develop and, if approved, commercialize casdatifan (International Nonproprietary Name; development code: AB521), an investigational small molecule HIF (Hypoxia Inducible Factor)-2α inhibitor, in Japan and certain other territories in Asia (excluding mainland China). This option exercise is based on a 2017 option and license agreement between Taiho and Arcus. This is the fifth option exercise by Taiho to an Arcus program.

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In exchange for the exclusive license to casdatifan, Taiho will make an option exercise payment, as well as additional payments upon achievement of clinical, regulatory and commercialization milestones, and, if any products from the program are approved, will pay royalties on net sales of such products.

Casdatifan is an investigational small molecule compound developed by Arcus. Arcus is currently conducting an ongoing global, registrational Phase 3 study, PEAK-1,* comparing the combination therapy of casdatifan and a VEGFR-targeted tyrosine kinase inhibitor (TKI) to monotherapy using a VEGFR-targeted TKI alone in patients with clear cell renal cell carcinoma (ccRCC). Japan is also expected to participate in the study starting in the first half of 2026.

*PEAK-1: A Randomized, Placebo-Controlled, Double-Blind, Multicenter Phase 3 Trial of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients with Advanced Clear Cell Renal Cell Carcinoma

Through this collaboration, Taiho and Arcus are committed to delivering casdatifan as a potentially innovative new medicine to patients and healthcare professionals as swiftly as possible.

About Casdatifan (AB521)

Casdatifan is a small-molecule inhibitor of HIF-2α, a master switch that turns on hundreds of genes in response to low oxygen levels; when oxygen levels return to normal, HIF-2α is turned off. In a majority of people with the most common form of kidney cancer (clear cell renal cell carcinoma), this shut-off mechanism is deficient and HIF-2α remains activated even in the presence of oxygen, causing normal kidney cells to become cancerous. Casdatifan is designed to provide deeper and more durable inhibition of the HIF-2α pathway.

About clear cell renal cell carcinoma (ccRCC)

Kidney cancer is a disease with a rising worldwide incidence estimated at 400,000 new cases annually, and a worldwide mortality rate approaching 175,000 deaths per year. Current projections suggest incidence continuing to increase over the next decade, emphasizing the urgency of addressing this significant global health trend. ccRCC is the most common type of kidney cancer in adults, making up 75-80% of all cases.

(Press release, Taiho, OCT 19, 2025, View Source [SID1234656800])

On October 19, 2025 Astrazeneca and Daiichi Sankyo reported positive results from the TROPION-Breast02 Phase III trial showed Datroway (datopotamab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement for the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to investigator’s choice of chemotherapy as 1st-line treatment for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option.

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These late-breaking results will be presented today during a Proffered Paper session at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Berlin, Germany (abstract #LBA21).

Datroway demonstrated a 5.0-month improvement in median OS compared to chemotherapy (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.64-0.98; p=0.0291). Median OS was 23.7 months for patients treated with Datroway versus 18.7 months for those treated with chemotherapy.

Datroway reduced the risk of disease progression or death by 43% compared to chemotherapy (HR 0.57; 95% CI 0.47-0.69; p<0.0001) as assessed by blinded independent central review (BICR). Median PFS was 10.8 months for patients treated with Datroway versus 5.6 months for those treated with chemotherapy.

In addition to patients whose tumours did not express PD-L1, TROPION-Breast02 enrolled patients with PD-L1 expressing tumours for whom immunotherapy was not an option due to other factors.

Rebecca Dent, MD, FRCP, Professor and Deputy Chief Executive Officer, National Cancer Centre Singapore, and principal investigator for the trial, said: "In TROPION-Breast02, datopotamab deruxtecan meaningfully extended patients’ lives and nearly doubled their time without disease progression. These are significant outcomes for patients with metastatic triple-negative breast cancer who are not suitable candidates for immunotherapy, and remarkable results considering the trial included a subset of patients with highly aggressive disease who are often excluded from research in this setting."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "The TROPION-Breast02 results show for the first time that these triple-negative breast cancer patients may have an alternative to chemotherapy in the 1st-line setting that can both delay the progression of their disease and prolong their lives. For Datroway to have so significantly improved patient outcomes in the 1st-line metastatic setting as monotherapy also gives us great confidence in its potential in combination with Imfinzi, and in the early-stage, potentially curative setting where our next studies are ongoing."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "Patients with metastatic triple-negative breast cancer have one of the worst prognoses of any breast cancer subtype, and for those who are not candidates for immunotherapy, chemotherapy has long been the 1st-line standard of care. The TROPION-Breast02 results show Datroway has the potential to replace traditional chemotherapy in this setting and to meaningfully improve survival of patients."

Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Summary of efficacy results

Datroway (n=323)

ICC (n=321)

Median OS, months (95% CI)

23.7 (19.8-25.6)

18.7 (16.0-21.8)

HR (95% CI)

0.79 (0.64-0.98)

p-value

0.0291

Median PFS by BICR, months (95% CI)

10.8 (8.6-13.0)

5.6 (5.0-7.0)

HR (95% CI)

0.57 (0.47-0.69)

p-value

<0.0001

Median PFS by investigator, months (95% CI)

9.6 (7.4-11.2)

5.2 (4.2-5.6)

HR (95% CI)

0.56 (0.47-0.67)

Confirmed ORR, %

62.5

29.3

CR, % (n)

9.0 (29)

2.5 (8)

PR, % (n)

53.6 (173)

26.8 (86)

Median DoR, months (95% CI)

12.3 (9.1-15.9)

7.1 (5.6-8.9)

As of 25 August 2025, data cut-off, 45 patients (14%) remained on Datroway and 8 patients (3%) on chemotherapy.
BICR, blinded independent central review; CI, confidence interval; CR, complete response; DoR, duration of response; HR, hazard ratio; ICC, investigator’s choice of chemotherapy; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response

Patients receiving Datroway were on treatment more than twice as long as those receiving chemotherapy (median duration of treatment of 8.5 versus 4.1 months) and experienced a lower rate of treatment-related adverse events (TRAEs) associated with discontinuation (4% versus 7%). Grade 3 or higher TRAEs occurred in 33% and 29% of patients in the Datroway and chemotherapy arms, respectively. The most common Grade 3 or higher TRAEs were neutropenia (3%, 13%), stomatitis (8%, 0%), leukopenia (<1%, 4%), fatigue (3%, 3%), vomiting (1%, <1%), anaemia (2%, 3%), alopecia (0%, <1%), peripheral neuropathy (0%, 2%), dry eye (1%, 0%), nausea (<1%, <1%), decreased appetite (<1%, <1%) and constipation (<1%, 0%). There was one Grade 5 interstitial lung disease (ILD) event in the Datroway arm adjudicated as drug-related by an independent committee. This event was characterised as Grade 3 pneumonitis and cause of death was attributed to disease progression by the treating investigator.

AstraZeneca and Daiichi Sankyo will also present updated results from the BEGONIA Phase Ib/II trial at ESMO (Free ESMO Whitepaper) showing Datroway in combination with Imfinzi (durvalumab) continued to demonstrate robust anti-tumour activity as 1st-line treatment for patients with metastatic TNBC across PD-L1 expression levels and specifically in those with high PD-L1-expressing tumours. These results will be presented on Monday, 20 October (abstract #555MO).

AstraZeneca and Daiichi Sankyo are evaluating Datroway across stages and treatment settings of TNBC in three additional Phase III trials. TROPION-Breast03 is evaluating Datroway with or without Imfinzi in patients with Stage I-III TNBC with residual invasive disease after neoadjuvant systemic therapy. TROPION-Breast04 is evaluating neoadjuvant Datroway plus Imfinzi in patients with Stage II-III triple-negative or hormone receptor (HR)-low, HER2-low or -negative breast cancer. TROPION-Breast05 is evaluating 1st-line Datroway with or without Imfinzi in patients with metastatic TNBC whose tumours express PD-L1.

Notes

Triple-negative breast cancer
TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.1,2 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.3-5 Metastatic TNBC is the most aggressive type of breast cancer and has one of the worst prognoses, with median OS of just 12 to 18 months and only about 14% of patients living five years following diagnosis.3,6,7

While some breast cancers may test positive for oestrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.3 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.3 For patients with metastatic disease with PD-L1 expressing tumours, the addition of immunotherapy to chemotherapy has improved outcomes in the 1st-line setting.8,9 However, for the approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy remains the 1st-line standard of care.10,11

TROP2 is a protein broadly expressed in several solid tumours including TNBC.12 TROP2 is associated with increased tumour progression and poor survival in patients with breast cancer.13,14

TROPION-Breast02
TROPION-Breast02 is a global, multicentre, randomised, open-label Phase III trial evaluating the efficacy and safety of Datroway versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumours did not express PD-L1 as well as patients with PD-L1 expressing tumours who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrolment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as stable brain metastases.

The dual primary endpoints of TROPION-Breast02 are PFS as assessed by BICR and OS. Key secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response, disease control rate, pharmacokinetics and safety.

TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For more information, visit ClinicalTrials.gov.

Datroway
Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the US only) is a TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Datroway is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datroway is approved in more than 35 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on results from the TROPION-Breast01 trial.

Datroway is available in the US under accelerated approval for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy based on results from the TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. Datroway is approved in Russia for the same population.

(Press release, AstraZeneca, OCT 19, 2025, View Source [SID1234656785])

On October 19, 2025 Incyte (Nasdaq:INCY) reported the first clinical data evaluating its TGFβR2×PD-1 bispecific antibody (INCA33890) for patients with microsatellite stable (MSS) colorectal cancer; and its potent, selective and orally bioavailable KRAS G12D inhibitor (INCB161734) for patients with KRAS G12D mutations, specifically pancreatic ductal adenocarcinoma (PDAC). The data were featured in two oral sessions (Investigational immunotherapy; Abstract #1522MO and Developmental therapeutics; Abstract #916O, respectively) at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025.

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"The proof-of-concept data highlight the potential of INCA33890 and INCB161734 to address significant medical needs in patients with advanced solid tumors, including MSS colorectal cancer and PDAC," said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. "These results, including the favorable safety profiles as monotherapies, support continued clinical development. We look forward to exploring the development of these two novel targeted therapies in combination with current standard of care as frontline treatments."

INCA33890 (TGFβR2×PD-1)​

In an October 17, 2025, mini oral session at ESMO (Free ESMO Whitepaper), data were presented from the monotherapy arm (Part 1) of the INCA33890 Phase 1 trial, which included patients with advanced or metastatic solid tumors – including MSS colorectal cancer, ovarian cancer (OC), squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), gastric/gastroesophageal junction cancer (GC/GEJ) and PDAC – who experienced disease progression after receiving available therapies or were intolerant to, ineligible for or declined standard treatments, including immune checkpoint inhibitors. These patients received doses of INCA33890 ranging from 100 mg to 1,500 mg every two weeks (Q2W) to 900 mg intravenously (IV) every four weeks (Q4W) in continuous 28-day cycles. INCA33890 300 mg, 600 mg and 900 mg Q2W were selected as the recommended doses for expansion (RDE).

Initial data (cut-off July 25, 2025) showed promising clinical efficacy with INCA33890 treatment. This trial is ongoing, and the data will continue to mature. Of note:

INCA33890 demonstrated a manageable safety profile across all enrolled patients (n=260) – the occurrence and severity of immune related adverse reactions was similar to approved immune checkpoint inhibitors. The most common treatment-related adverse events (TRAEs) among individuals treated with INCA33890 across RDE (n=239) were fatigue (13.8%), pruritus (8.8%) and infusion-related reactions (8.4%).
Among patients with metastatic MSS colorectal cancer treated with INCA33890 at RDE (n=105), the vast majority (93.3%) had received more than two prior treatment regimens and 71.4% had active liver metastases at the time of treatment.
Within this cohort, 16 patients treated with INCA33890 responded (14 confirmed), with 15.2% achieving an objective response rate (ORR) and a median duration of therapy of 7.3 months.
The ORR among metastatic MSS colorectal cancer patients treated with INCA33890 was similar across RDE. Deep tumor responses were observed among patients with liver metastasis (n=9) – 12.0% achieved an ORR with a disease control rate (DCR) of 20.0%. Additionally, seven patients with no liver metastases treated with INCA33890 responded, achieving an ORR of 23.3% and DCR of 50.0%.
"Increased TGFβR2 expression is associated with poor prognosis in multiple solid tumor types, including colorectal cancer, which is third most common cancer and the second leading cause of cancer-related mortality worldwide," said Elena Garralda, M.D., Ph. D., Trial Investigator and Director of Early Drug Development at the Vall d’Hebron Institute of Oncology. "The efficacy data presented at ESMO (Free ESMO Whitepaper) in MSS colorectal cancer, coupled with tolerable safety profile, provide proof of concept for this differentiated approach of on-target inhibition of the TGF-β pathway. I look forward to seeing further development of this promising drug."

Evaluation of INCA33890 900 mg Q2W in combination with standard of care (SoC) treatments in patients with MSS colorectal cancer is ongoing. Dose escalation has been completed across combination therapy cohorts and no DLTs were identified. Incyte plans to initiate a registrational program for INCA33890 in MSS colorectal cancer in 2026.

INCB161734 (KRAS G12D)​

In an October 19, 2025, proffered paper session, data were presented from the monotherapy arm (Part 1) of the INCB161734 Phase 1 trial in patients with select advanced or metastatic solid tumors and documented KRAS G12D mutation – including PDAC, colorectal cancer, NSCLC, OC and other solid tumors – who received varying doses of INCB161734 ranging from 200 mg to 1,600 mg daily. The dose escalation portion of the study is complete – two doses, 600 mg daily and 1,200 mg daily, were selected for expansion.

Preliminary data (cut-off August 1, 2025) demonstrated evidence of clinical benefit in advanced or metastatic PDAC patients treated with INCB161734 (n=83). This trial is ongoing, and the data will continue to mature. Specifically:

INCB161734 demonstrated a manageable safety profile across all treated patients (n=136). No DLTs were reported in dose escalation, and the maximum tolerated dose (MTD) was not reached. No fatal adverse events (AEs) were considered related to treatment. The most common TRAEs across tumor types, nausea (58.1%), diarrhea (50.7%), vomiting (45.6%) and fatigue (17.4%), were mostly Grade 1.
PDAC patients receiving 600 mg (n=25) and 1,200 mg (n=29) INCB161734 daily demonstrated objective response rates (ORR; 20% and 34%) and high DCRs (64% and 86%). The study is ongoing for the majority of patients; data on durability of response is expected in the first half of 2026.
"PDAC is a highly aggressive cancer, and patients with G12D-mutated PDAC currently have an average five-year survival rate of less than ten percent," said Dr. Jayesh Desai, Tiral Investigator, Medical Oncologist and Associate Director of Clinical Research at the Peter MacCallum Cancer Centre. "It is encouraging to see promising antitumor activity and strong molecular response with INCB161734 monotherapy in this heavily pretreated patient population, and I believe these data speak to the potential of INCB161734 to be an impactful, selective targeted therapy for PDAC."

Evaluation of the data for INCB161734 in patients with PDAC is ongoing with results expected in 2026. Based on the findings, the company will conduct a comprehensive review of the data to inform next steps for the program, including discussions with regulatory authorities.

More information regarding the 2025 ESMO (Free ESMO Whitepaper) Congress and the data from Incyte’s oncology portfolio being featured at the meeting can be found on the ESMO (Free ESMO Whitepaper) website: View Source

Analyst Event and Webcast
The data from the ESMO (Free ESMO Whitepaper) oral presentations and additional results from INCA33890 in patients with MSS colorectal cancer and INCB161734 in patients with PDAC will also be discussed at an in-person analyst and investor event on Sunday, October 19, 2025, from 1:30 – 3:00 p.m. ET (7:30 – 9:00 p.m. CEST) at ESMO (Free ESMO Whitepaper).

The event will be webcasted and can be accessed via the Events and Presentations tab of the Investor section of Incyte.com and it will be available for replay for 30 days.

More information regarding the 2025 ESMO (Free ESMO Whitepaper) Congress can be found at: View Source

About INCA33890
INCA33890 is an investigational, TGFβR2×PD-1 bispecific antibody, developed in collaboration with Merus using their Biclonics antibody platform, engineered to block TGF-β–mediated signaling in T cells co-expressing TGF-β and PD-1. TGFβ is known to promote cancer immune evasion and predicts poor response to PD-(L)1 targeted therapies. INCA33890 aims to spare tissues where TGF-β signaling is important for normal function, avoiding the known toxicity of a broad blocking of the TGF-β pathway. INCA33890 offers a promising targeted treatment strategy for patients with advanced or metastatic solid tumors, including microsatellite stable colorectal cancer.1,2,3,4

The open-label, multicenter Phase 1 study (NCT05836324) is evaluating the safety, tolerability, dose-limiting toxicities (DLTs), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of INCA33890 when administered as a monotherapy and in combination with other standard-of-care treatments (i.e., bevacizumab, bevacizumab and FOLFIRI, bevacizumab and FOLFOX, and cetuximab) in adults (≥18 years old) with advanced or metastatic solid tumors.

The study includes Part 1 evaluating INCA33890 as a monotherapy with Part 1A (dose escalation) and Part 1B (dose expansion). Inclusion criteria for Part 1 requires patients to have experienced disease progression after receiving available therapies or that they were intolerant to, ineligible for or declined standard treatment. Part 2 will evaluate INCA33890 administered in combination with other protocol-defined treatment(s) based on cohort assignment and also includes dose escalation (Part 2A) and dose expansion (Part 2B).

Primary endpoints include evaluating DLTs up to 28 days and safety/tolerability. Key secondary endpoints focus on preliminary efficacy (i.e., objective response rate [ORR], disease control rate [DCR], duration of response [DOR]) up to two years and PK parameters.

For more information about the study, please visit: View Source

About INCB161734
INCB161734 is an investigational novel, selective and orally bioavailable small molecule inhibitor targeting G12D-mutated KRAS. KRAS is one of the most frequently altered driver oncogenes in solid tumors. The G12D mutation, which represents approximately 40% of oncogenic KRAS mutations in patients with PDAC, is associated with aggressive tumor phenotypes and poor clinical outcomes.

The open-label, dose-escalation and dose-expansion Phase 1 study (NCT06179160) is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of INCB161734 when administered as monotherapy and in combination with other anticancer therapies in patients with advanced or metastatic solid tumors harboring the KRAS G12D mutation. The study includes Part 1 evaluating INCB161734 as a monotherapy, with Part 1A (dose escalation), Part 1B (cohort dose expansion), Part 1C (pharmacodynamics) and Part 1D (food-effect). Part 2 will evaluate INCA161734 administered in combination with other protocol-defined treatment(s) based on cohort assignment and also includes dose escalation (Part 2A) and dose expansion (Part 2B).

Primary endpoints include DLTs and TEAEs. Key secondary endpoints include objective ORR, DCR, DOR and PK parameters.

For more information about the study, please visit: View Source

(Press release, Incyte, OCT 19, 2025, View Source [SID1234656801])