What is IBI354 and how does it work against HER2-positive breast cancer?

IBI354 is a novel antibody-drug conjugate (ADC) comprised of trastuzumab conjugated to a camptothecin derivative. It selectively binds to tumors, internalizes, releases a cytotoxic payload, inhibits topoisomerase 1 activity, and induces a bystander effect to kill neighboring cancer cells.

What are the common side effects associated with IBI354 treatment?

the moast common treatment-emergent adverse events (TEAEs) included any-grade adverse effects, which occurred in 97.6% of patients. Grade 3 or higher TEAEs were observed in 39.1% of patients. Treatment-related interstitial lung disease was reported in 1.9% of patients.

What is the disease control rate (DCR) observed with IBI354 treatment?

The disease control rate (DCR) was 90.9% in evaluable patients with HER2-positive breast cancer. In patients treated with IBI354 at a dose of 9 mg/kg once every 3 weeks, the DCR was 89.7%.

Who is the lead author of the IBI354 study presented at ASCO 2025?

The lead study author is Charlotte Rose Lemech, BSc, FRACP, MBBS, of Scientia Clinical Research at UNSW Sydney in Australia.

What is raludotatug deruxtecan (R-DXd)?

Raludotatug deruxtecan (R-DXd) is an antibody-drug conjugate (ADC) designed to target and treat ovarian cancer cells expressing cadherin-6 (CDH6). It combines a humanized anti-CDH6 antibody with a TOPO I inhibitor payload.

What were teh key findings of the phase 1 trial of R-DXd in platinum-sensitive ovarian cancer?

The phase 1 trial demonstrated a confirmed overall response rate (ORR) of 72.2% in patients with platinum-sensitive ovarian cancer treated with R-DXd. In patients who had progressed on a prior PARP inhibitor, the ORR was 58.3%.

What is platinum-sensitive ovarian cancer?

Platinum-sensitive ovarian cancer refers to cancer that initially responds to platinum-based chemotherapy but later relapses more than six months after the completion of treatment.

what are the common side effects associated with raludotatug deruxtecan treatment?

The most common treatment-emergent adverse events (TEAEs) associated with R-DXd include nausea, anemia, fatigue, and urinary tract infection. Some patients also experienced more serious side effects such as decreased neutrophil count and interstitial lung disease.

What is the meaning of CDH6 expression in ovarian cancer?

Cadherin-6 (CDH6) is a protein expressed in a important percentage of ovarian cancers, making it a potential target for therapies like raludotatug deruxtecan. However, the study did not show a strong correlation between CDH6 expression levels and clinical benefit.

What is the next step in the growth of raludotatug deruxtecan for ovarian cancer?

Based on the promising results of the phase 1 trial, further development and exploration of raludotatug deruxtecan in platinum-sensitive ovarian cancer is warranted. additional studies are expected to further evaluate it's efficacy and safety.

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antibody-drug conjugate

Q: What were the key findings of the phase 1 trial for IBI354 in HER2-positive breast cancer?

The phase 1 trial demonstrated that IBI354 was safe and exhibited antitumor activity in patients with pretreated HER2-positive advanced breast cancer. The overall response rate (ORR) was 59.1% in evaluable patients.

Q: What is the overall response rate (ORR) observed with IBI354 treatment?

In evaluable patients with HER2-positive breast cancer, the overall response rate (ORR) was 59.1%.In a subset of patients treated with a 9 mg/kg dose of IBI354, the ORR was even higher at 72.4%.

Health

Antibody-drug conjugate in progressive metastatic castration-resistant prostate cancer

by Dr. Michael Lee – Health Editor October 13, 2025

written by Dr. Michael Lee – Health Editor

FOR46 ⁢Shows ‍Promise in Advanced Prostate Cancer, Phase I Trial⁤ Reports

A first-in-human phase I study⁢ indicates the antibody-drug conjugate FOR46 demonstrates encouraging clinical activity and a manageable safety profile in patients with metastatic, castration-resistant prostate cancer (mCRPC) who have progressed following treatment with androgen pathway signaling inhibitors. The⁢ findings, recently presented, ‌suggest FOR46 warrants further examination.

FOR46 is a fully human antibody linked to the cytotoxic agent monomethyl auristatin E. It specifically targets CD46, a protein overexpressed on mCRPC cells. Preclinical studies demonstrated⁤ strong activity of FOR46 in models of enzalutamide-resistant CRPC.

The phase I trial enrolled 56 patients, initially receiving a 0.1 mg/kg loading dose of FOR46 intravenously every three weeks.The‍ study’s primary‌ goal was to determine the maximum ⁣tolerated dose (MTD).‌ Researchers utilized whole blood mass cytometry to analyze ⁣the peripheral‍ immune response and assessed CD46 expression in ‌tumor tissue via central pathology review.

Dose-limiting toxicities observed included ⁢neutropenia in four patients, febrile neutropenia in one, and fatigue in one. The established MTD was 2.7‍ mg/kg. Across all dose levels,‌ the most frequently reported adverse events⁤ (Grade ≥3) were ⁢neutropenia (59%), leukopenia⁤ (27%), lymphopenia (7%), anemia (7%), and ⁢fatigue (5%). One instance of grade 3 febrile neutropenia occurred; no treatment-related deaths were reported.

Analysis of an efficacy-evaluable⁣ subgroup-40⁣ patients with adenocarcinoma treated ‌with a starting dose‍ of ≥1.2 mg/kg-revealed a median radiographic progression-free survival of 8.7 months (range: 0.1-33.9). Among 39 patients with evaluable data, 36% (14 patients) experienced‌ a ≥50% reduction in prostate-specific antigen (PSA). The confirmed overall response rate,based on RECIST criteria,was 20% (5 ⁤of 25 assessable patients),with‍ a median⁢ duration of response ⁤of 7.5 months.

Notably,responders exhibited a considerably higher frequency of circulating effector ‌CD8⁺-T cells during treatment.Researchers concluded that targeting CD46 with⁣ FOR46 appears to stimulate an ⁣immune response correlated with⁤ clinical benefit.

October 13, 2025 0 comments

Health

IBI354 ADC Shows Promise in HER2+ Breast Cancer After Prior Treatment

by Dr. Michael Lee – Health Editor June 28, 2025

written by Dr. Michael Lee – Health Editor

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IBI354 Shows promise in Treating HER2-Positive Breast Cancer: ASCO 2025 Update

Table of Contents

IBI354 Shows promise in Treating HER2-Positive Breast Cancer: ASCO 2025 Update

Chicago, IL – Updated findings from a phase 1 clinical trial, presented at the 2025 ASCO Annual Meeting, reveal that the novel antibody-drug conjugate (ADC) IBI354 demonstrates both safety and meaningful antitumor activity in patients with pretreated HER2-positive advanced breast cancer. The data offers a beacon of hope for individuals with limited treatment options for this aggressive form of cancer.

IBI354 Efficacy in HER2-Positive Breast Cancer

The trial, identified as NCT05636215, evaluated the efficacy of IBI354 in patients with HER2-positive breast cancer. The results are encouraging. Evaluable patients (n = 88) achieved an overall response rate (ORR) of 59.1% (95% CI, 48.1%-69.5%). This included a complete response rate of 4.5% and a partial response (PR) rate of 54.5%. The stable disease (SD) and progressive disease (PD) rates were 31.8% and 9.1%, respectively. The disease control rate (DCR) was a notable 90.9% (95% CI, 82.9%-96.0%).

Did You Know? The five-year survival rate for metastatic HER2-positive breast cancer has considerably improved over the past two decades, rising from approximately 20% to over 40%, thanks to targeted therapies like trastuzumab and pertuzumab, according to a 2023 report in the journal *Targeted Oncology*.

Notably, in a subset of patients with HER2-positive breast cancer treated with IBI354 at a dose of 9 mg/kg once every 3 weeks (n = 29), the ORR climbed to 72.4% (95% CI, 52.8%-87.3%), comprised exclusively of PRs. The SD and PD rates were 17.2% and 10.3%, respectively, and the DCR was 89.7% (95% CI, 72.6%-97.8%).

Safety Profile of IBI354

The safety population of the trial (n = 368) included patients with breast cancer and other HER2-positive solid tumors. Any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.6% of patients, and 39.1% of patients experienced grade 3 or higher TEAEs. The rates of any-grade and grade 3 or higher treatment-related AEs (TRAEs) were 90.8% and 27.4%, respectively. Serious AEs and treatment-related serious AEs occurred at rates of 20.7% and 9.0%, respectively.

TEAEs led to treatment interruption,treatment reduction,and treatment discontinuation in 26.9%, 2.7%, and 1.9% of patients, respectively. One patient (0.3%) died due to TEAEs, but no deaths were attributed to TRAEs.Treatment-related interstitial lung disease was reported in 1.9% of patients.

Pro Tip: Patients undergoing treatment with IBI354 should be closely monitored for any signs of adverse events, notably respiratory symptoms, and should promptly report any concerns to their healthcare provider.

IBI354: Mechanism of Action

IBI354 is a novel ADC composed of trastuzumab (Herceptin) conjugated to a camptothecin derivative. Its mechanisms of action include selective binding of the antibody to the tumor, internalization of the agent, lysosomal degradation, release of the cytotoxic payload, inhibition of topoisomerase 1 activity to induce DNA damage and cell apoptosis, and a bystander effect to kill neighboring cancer cells.

Trial Design and Patient Population

The global, multicenter, phase 1 study enrolled patients with advanced breast cancer and other solid tumors with HER2 expression or gene alterations who had progressed on or were intolerant to standard therapies. Breast cancer patients needed to have a HER2 expression of immunohistochemistry (IHC) 2+/in situ hybridization+ or IHC 3+.

Enrolled patients received IBI354 at doses ranging from 0.8 mg/kg to 18 mg

June 28, 2025 0 comments

Business

Raludotatug Deruxtecan: Hope for Platinum-Sensitive Ovarian Cancer

by Priya Shah – Business Editor June 21, 2025

written by Priya Shah – Business Editor

Raludotatug Deruxtecan Shows Promise in treating Ovarian Cancer

Table of Contents

Raludotatug Deruxtecan Shows Promise in treating Ovarian Cancer

New data from a phase 1 clinical trial indicates that raludotatug deruxtecan (R-DXd) is a potentially effective treatment for platinum-sensitive ovarian cancer.The study, presented at the ESMO Gynaecological Cancers Congress 2025, showed promising results in heavily pretreated patients, offering a new avenue for those with limited options.

Significant Response Rates Observed

The trial (NCT04707248) subgroup analysis focused on patients with platinum-sensitive ovarian cancer, a condition where the cancer responds to initial platinum-based chemotherapy but later relapses. The results were encouraging:

In the platinum-sensitive subgroup (n = 18), the confirmed overall response rate (ORR) was 72.2% (95% CI, 46.5%-90.3%), consisting entirely of partial responses (PRs).
the stable disease (SD) rate was 16.7%.
For patients with platinum-sensitive disease who had previously progressed on a PARP inhibitor (n = 12), the ORR was 58.3% (95% CI, 27.7%-84.8%),also consisting of all PRs.

Kathleen Moore, MD, from the University of Oklahoma Health Sciences Center, highlighted the significance of these findings, stating that the data supports further inquiry of raludotatug deruxtecan in this patient population.

Did You Know? ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. The American Cancer Society estimates that in 2024,about 19,710 women will receive a new diagnosis of ovarian cancer,and about 12,730 women will die from ovarian cancer. American Cancer Society

Understanding Raludotatug Deruxtecan (R-DXd)

Raludotatug deruxtecan is an antibody-drug conjugate (ADC) that targets cadherin-6 (CDH6), a protein expressed in a significant proportion (65% to 85%) of ovarian cancers. The ADC consists of a humanized anti-CDH6 monoclonal antibody linked to a TOPO I inhibitor payload via a cleavable linker.

The phase 1 trial was conducted in two parts: a dose-escalation phase (part A) and a dose-expansion phase (part B). Patients with previously treated ovarian cancer received varying doses of R-DXd. The primary goals were to assess safety, tolerability, and determine the recommended dose for expansion. Secondary endpoints included pharmacokinetics, overall response rate, duration of response, and disease control rate.

Pro Tip: Antibody-drug conjugates (ADCs) represent a cutting-edge approach in cancer therapy, combining the specificity of antibodies with the potent cell-killing ability of cytotoxic drugs. This targeted delivery minimizes damage to healthy cells, potentially reducing side effects.

Trial Design and Patient Eligibility

The phase 1 trial enrolled patients with advanced or metastatic ovarian cancer who had received prior taxane and platinum-based chemotherapy. Patients were required to have an ECOG performance status of 0 to 1 and could not have received prior CDH6-targeting agents or ADCs linked to a TOPO I inhibitor.

the study evaluated different dose levels of R-DXd,ranging from 1.6 mg/kg to 9.6 mg/kg in the dose-escalation phase and 4.8 mg/kg to 6.4 mg/kg in the dose-expansion phase. R-DXd was administered intravenously every three weeks.

Efficacy and Safety Data

The subgroup analysis presented at the ESMO Gynaecological cancers Congress focused on 18 patients with platinum-sensitive disease who received R-DXd at 4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg. Key efficacy outcomes included:

Disease control rate (DCR): 88.9% (95% CI, 65.3%-98.6%)
Clinical benefit rate (CBR): 77.8% (95% CI, 52.4%-93.6%)
Median time to response (TTR): 1.4 months (95% CI, 1.2-2.7)
median duration of response (DOR): 5.7 months (95% CI, 4.2-NE)
Median progression-free survival (PFS): 8.1 months (95% CI, 4.1-NE)

In patients who had progressed on a prior PARP inhibitor, the DCR was 83.3%, the CBR was 66.7%, the median TTR was 1.4 months, the median DOR was 5.1 months, and the median PFS was 7.1 months.

Regarding safety, all platinum-sensitive patients experienced treatment-emergent adverse events (TEAEs), with 77.8% experiencing grade 3 or higher TEAEs. The most common TEAEs included nausea, anemia, and fatigue. One patient experienced grade 2 treatment-related interstitial lung disease/pneumonitis.

Key Efficacy Outcomes in Platinum-Sensitive Ovarian Cancer
Outcome	Platinum-Sensitive (n=18)	Prior PARP Inhibitor Progression (n=12)
Overall Response Rate (ORR)	72.2%	58.3%
Disease Control Rate (DCR)	88.9%	83.3%
Median Progression-Free Survival (PFS)	8.1 months	7.1 months

Moore noted that the safety profile in the platinum-sensitive subgroup was consistent with the overall study population.

What are the potential long-term benefits of raludotatug deruxtecan for ovarian cancer patients? How might these findings influence future treatment strategies?

Ovarian Cancer: An evergreen Perspective

Ovarian cancer is often diagnosed at a late stage because early symptoms can be vague and easily overlooked. This late diagnosis contributes to poorer outcomes. Standard treatment involves surgery followed by platinum-based chemotherapy. Tho, many patients experience recurrence, necessitating further lines of therapy.

The development of targeted therapies like raludotatug deruxtecan represents a significant advancement in ovarian cancer treatment. By targeting specific proteins expressed on cancer cells, these therapies offer the potential for more effective and less toxic treatment options. the ongoing research and development in this field are crucial for improving outcomes for women with ovarian cancer.

Frequently asked Questions About Raludotatug Deruxtecan and Ovarian Cancer

What is the prognosis for women with platinum-sensitive recurrent ovarian cancer?

The prognosis for women with platinum-sensitive recurrent ovarian cancer varies depending on several factors, including the time as their last platinum-based chemotherapy, their overall health, and the specific characteristics of their cancer. While platinum-based chemotherapy can be effective in these cases, resistance often develops over time, leading to the need for alternative treatment options.

how does raludotatug deruxtecan compare to other treatments for recurrent ovarian cancer?

Raludotatug deruxtecan is a novel antibody-drug conjugate that targets CDH6, a protein frequently expressed in ovarian cancer cells. Unlike customary chemotherapy, which affects all rapidly dividing cells, raludotatug deruxtecan is designed to selectively target and kill cancer cells expressing CDH6, potentially leading to fewer side effects and improved efficacy.

What are the potential benefits of participating in clinical trials for ovarian cancer?

Participating in clinical trials offers several potential benefits for ovarian cancer patients. It provides access to cutting-edge treatments that are not yet widely available, contributes to the advancement of medical knowledge, and may improve outcomes for both current and future patients. Clinical trials are carefully designed to ensure patient safety and are conducted under strict ethical guidelines.

How can women reduce their risk of developing ovarian cancer?

While there is no guaranteed way to prevent ovarian cancer, several factors have been associated with a reduced risk. These include using oral contraceptives, having a tubal ligation or hysterectomy, and breastfeeding. Women with a family history of ovarian or breast cancer shoudl consider genetic testing to assess their risk and discuss preventive measures with their healthcare provider.

What resources are available for women with ovarian cancer and their families?

There are numerous resources available for women with ovarian cancer and their families, including support groups, educational materials, and financial assistance programs.Organizations such as the Ovarian Cancer Research Alliance (OCRA) and the National Ovarian Cancer Coalition (NOCC) provide valuable data and support to patients and their loved ones.

Disclaimer: This article provides information about a clinical trial and potential treatment options for ovarian cancer.It is indeed not intended to provide medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment recommendations.

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June 21, 2025 0 comments