On October 20, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported new long-term data highlighting the sustained survival benefits of KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in treating non-small cell lung cancer (NSCLC). The results are based on the exploratory five-year analyses of KEYNOTE-671 evaluating KEYTRUDA as part of a neoadjuvant followed by adjuvant (perioperative) treatment regimen for patients with resectable NSCLC; and the eight-year analyses of KEYNOTE-024 and -042 and the 10-year analyses of KEYNOTE-001 and -010 evaluating KEYTRUDA as monotherapy in certain patients with locally advanced or metastatic NSCLC.

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"These long-term data mark a milestone for patients and their families and build upon the transformative progress we’ve already made in non-small cell lung cancer," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "Across the spectrum of earlier to advanced stages of disease, these results support the long-term survival benefit of KEYTRUDA in certain patients with NSCLC. We look forward to continued advancements and possibilities for KEYTRUDA in cancer treatment."

In the exploratory five-year follow-up data from the Phase 3 KEYNOTE-671 trial, KEYTRUDA in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery continued to show clinically meaningful improvements in overall survival (OS) and event-free survival (EFS) outcomes in certain patients with resectable stage II, IIIA or IIIB NSCLC, compared to neoadjuvant placebo plus chemotherapy followed by adjuvant placebo alone. The hazard ratio (HR) for OS for the KEYTRUDA regimen versus the chemotherapy-placebo regimen was 0.74 (95% CI, 0.59-0.92). For EFS, the HR for the KEYTRUDA regimen versus the chemotherapy-placebo regimen was 0.58 (95% CI, 0.48-0.69).

"The five-year benefit demonstrated across overall survival and event-free survival from KEYNOTE-671 supports the continued use of this pembrolizumab-based perioperative regimen as a standard of care for patients with resectable, earlier-stage non-small cell lung cancer," said Dr. Heather Wakelee, principal investigator for KEYNOTE-671, thoracic medical oncologist. "These consistent results are impactful, as they reflect the importance of intervening for certain patients with earlier stages of non-small cell lung cancer." Wakelee is also a professor of medicine at Stanford Medicine.

In the exploratory eight-year analyses from KEYNOTE-024 and KEYNOTE-042 and the exploratory 10-year analyses from KEYNOTE-001 and KEYNOTE-010, KEYTRUDA continued to improve OS in patients with locally advanced or metastatic NSCLC compared to chemotherapy.

In KEYNOTE-001, the median OS for patients receiving KEYTRUDA was 13.2 months (95% CI, 10.5-15.3) in those with any Tumor Proportion Score (TPS) and a median OS of 17.3 months (95% CI,13.7-24.8) in those with a TPS ≥50%. KEYNOTE-001 did not compare KEYTRUDA to another agent or placebo.
In KEYNOTE-010, the median OS for patients receiving KEYTRUDA with a TPS ≥1% was 11.8 months (95% CI, 10.3-13.0) versus 8.3 months (95% CI, 7.5-9.5) for chemotherapy (HR=0.66 [95% CI, 0.58-0.76]). For patients receiving KEYTRUDA, with a TPS ≥50%, the median OS was 16.6 months (95% CI, 12.1-21.2) versus 8.2 months (95% CI, 6.4-9.8) for chemotherapy (HR=0.55 [95% CI, 0.44-0.68]).
In KEYNOTE-024, the median OS for patients receiving KEYTRUDA with a TPS ≥50% was 26.3 months (95% CI,18.3-40.4) versus 13.4 months (95% CI, 9.4-18.3) for chemotherapy (HR=0.65 [95% CI, 0.50-0.83]).
In KEYNOTE-042, the median OS for patients receiving KEYTRUDA with a TPS ≥1% was 16.4 months (95% CI, 14.0-19.6) versus 12.1 months (95% CI, 11.3-13.3) for chemotherapy (HR=0.78 [95% CI, 0.69-0.88]). For patients receiving KEYTRUDA with a TPS ≥50%, the median OS was 20.0 months (95% CI, 15.9-24.2) versus 12.2 months (95% CI, 10.4-14.6) for chemotherapy (HR=0.70 [95% CI, 0.59-0.83]).
Participants from KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042 who achieved a complete response after taking KEYTRUDA and then had progressive disease were eligible for a subsequent anti-cancer therapy including a second course of KEYTRUDA monotherapy.

Additional details about the study designs and results from KEYNOTE-671, KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042, including selected results of previously reported primary analyses, are described below.

"Historically, patients with advanced non-small cell lung cancer faced a poor prognosis, with long-term survival considered unlikely," said Edward B. Garon, MD, MS, professor of medicine, principal investigator for KEYNOTE-001, David Geffen School of Medicine, the University of California, Los Angeles. "The long-term results from these four trials show that pembrolizumab has helped change what certain patients with advanced NSCLC can hope to achieve."

To date, KEYTRUDA monotherapy or combination regimens have demonstrated sustained survival benefits of five years or more across multiple types of cancer, including certain types of metastatic NSCLC (KEYNOTE-189, KEYNOTE-407), melanoma (KEYNOTE-006, KEYNOTE-054), advanced head and neck (KEYNOTE-048), bladder (KEYNOTE-045) and endometrial (KEYNOTE-775) cancers.

The late-breaking five-year data from KEYNOTE-671 were presented during a mini oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 (Presentation #LBA67). The eight-year data from KEYNOTE-024 and KEYNOTE-042 and 10-year data from KEYNOTE-001 and KEYNOTE-010 were presented during a poster session at the ESMO (Free ESMO Whitepaper) Congress 2025 (Presentation #3208P).

Study design and additional five-year data from KEYNOTE-671

KEYNOTE-671 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial (ClinicalTrials.gov; NCT03425643) evaluating KEYTRUDA in combination with neoadjuvant chemotherapy, followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent, versus placebo plus neoadjuvant chemotherapy, followed by resection and adjuvant placebo, in patients with resectable stage II, IIIA or IIIB (T3-4N2) NSCLC (per the eighth edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual). The trial’s dual primary endpoints are EFS and OS. Key secondary endpoints include pathologic complete response (pCR) and major pathological response (mPR). The study enrolled 797 patients who were randomly assigned (1:1) to receive either:

KEYTRUDA (200 mg intravenously [IV] every three weeks) plus chemotherapy (cisplatin [75 mg/m2 , IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2 , IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4-12 weeks following surgery, KEYTRUDA (200 mg) was administered every three weeks for up to 13 cycles, or;
Placebo (saline IV every three weeks) plus chemotherapy (cisplatin [75 mg/m2 , IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4‑12 weeks following surgery, placebo was administered every three weeks for up to 13 cycles.
After a median follow-up of 60.4 months (range, 42.6-85.8), the five-year OS rate was 64.6% (95% CI, 59.5%-69.2%) for the KEYTRUDA regimen versus 53.6% (95% CI, 48.3%-58.6%) for the chemotherapy-placebo regimen. Median OS was not reached (NR) (95% CI, NR-NR) for patients who received the KEYTRUDA regimen versus 70.7 months (95% CI, 53.7-NR) for patients who received the chemotherapy-placebo regimen.

The five-year EFS rate was 49.9% (95% CI, 44.6%-55.0%) for the KEYTRUDA regimen versus 26.5% (95% CI, 21.7%-31.5%) for the chemotherapy-placebo regimen. Median EFS was 57.1 months (95% CI, 38.0-NR) for patients who received the KEYTRUDA regimen versus 18.4 months (95% CI, 14.8-22.1) for patients who received the chemotherapy-placebo regimen.

At the five-year follow-up analysis, Grade ≥3 treatment-related adverse events (TRAEs) occurred in 45.2% of patients receiving the KEYTRUDA regimen and 37.8% of patients receiving the chemotherapy-placebo regimen. Grade ≥3 immune-mediated adverse events (AEs) and infusion reactions occurred in 6.3% of patients receiving the KEYTRUDA regimen and 1.8% of patients receiving the chemotherapy-placebo regimen.

At the study’s previously reported primary analysis, KEYNOTE-671 showed that treatment with the KEYTRUDA regimen reduced the risk of death by 28% (HR=0.72 [95% CI, 0.56-0.93]; p=0.0103) versus the chemotherapy-placebo regimen. For patients who received the KEYTRUDA regimen, median OS was not reached (95% CI, NR-NR) versus 52.4 months (95% CI, 45.7-NR) for patients who received the chemotherapy-placebo regimen. Additionally, the KEYTRUDA regimen reduced the risk of EFS events by 42% (HR=0.58 [95% CI, 0.46-0.72]; p<0.0001) versus the chemotherapy-placebo regimen. For patients who received the KEYTRUDA regimen, median EFS was not reached (95% CI, 34.1-NR) versus 17.0 months (95% CI, 14.3-22.0) for patients who received the chemotherapy-placebo regimen.

(Press release, Merck & Co, OCT 20, 2025, View Source [SID1234656818])

Long-term follow-up data from exploratory analyses of KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042

In KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042, KEYTRUDA continued to improve OS compared to chemotherapy. In these studies, data showed KEYTRUDA improved OS compared to chemotherapy in patients whose tumors expressed PD-L1 (TPS ≥50%). Overall survival results from these long-term follow-up analyses showed:

KEYTRUDA

Chemotherapy

KEYNOTE-001a,b,c

Any TPS

n/N = 54/550

N/A

10y OS rate (95% CI), %

11.3% (8.5%-14.5%)

N/A

Median OS (95% CI), months

13.2 (10.5-15.3)

N/A

TPS ≥50%

n/N = 25/165

N/A

10y OS rate

19.3% (13.1%-26.5%)

N/A

Median OS (95% CI), months

17.3 (13.7-24.8)

N/A

KEYNOTE-010b,d

TPS ≥1%

n/N = 53/690

n/N = 9/343

10y OS rate

9.3% (7.0%-12.1%)

1.9% (0.7%-4.6%)

Median OS (95% CI), months

11.8 (10.3-13.0)

8.3 (7.5-9.5)

HR (95% CI)

0.66 (0.58–0.76)

TPS ≥50%

n/N = 35/290

n/N = 6/152

10y OS rate

15.5% (11.1%-20.5%)

2.7% (0.7%-7.4%)

Median OS (95% CI), months

16.6 (12.1-21.2)

8.2 (6.4-9.8)

HR (95% CI)

0.55 (0.44-0.68)

KEYNOTE-024a

TPS ≥50%

n/N = 36/154

n/N = 14/151

8y OS rate

24.3% (17.6%-31.5%)

12.8% (7.6%-19.3%)

Median OS (95% CI), months

26.3 (18.3-40.4)

13.4 (9.4-18.3)

HR (95% CI)

0.65 (0.50-0.83)

KEYNOTE-042a

TPS ≥1%

n/N = 66/637

n/N = 27/637

8y OS rate

12.0% (9.5%-14.8%)

4.7% (3.1%-6.9%)

Median OS (95% CI), months

16.4 (14.0-19.6)

12.1 (11.3-13.3)

HR (95% CI)

0.78 (0.69-0.88)

TPS ≥50%

n/N = 41/299

n/N = 13/300

8y OS rate

16.6% (12.5%-21.1%)

6.8% (4.1%-10.5%)

Median OS (95% CI), months

20.0 (15.9-24.2)

12.2 (10.4-14.6)

HR (95% CI)

0.70 (0.59-0.83)

n/N, number of patients in KEYNOTE-587/number of patients in parent study.

afirst-line therapy

bsecond-line+ therapy

cIn KEYNOTE-001, KEYTRUDA was not compared to any other agent or placebo.

dtwo doses of pembrolizumab treatment were combined for these analyses

Limited additional lung cancer-specific deaths occurred since the previously reported five-year data across all four trials.

At the conclusion of these initial studies, participants were eligible to transition to the KEYNOTE-587 extension study for long-term follow-up. The primary endpoint for KEYNOTE-587 is OS. For patients in KEYNOTE-587, the median time from first treatment in KEYNOTE-001 or randomization in KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042 to data cutoff was 124.6 months (range, 118.5-142.2), 115 months (range, 108.8-124.6), 106.4 months (range, 102.4-114.3) and 99 months (range, 86.6-110.2), respectively.

Study design and additional data from KEYNOTE-001

Ten-year outcomes for KEYTRUDA were measured in the Phase 1b KEYNOTE-001 trial (ClinicalTrials.gov; NCT01295827), which evaluated 550 patients with treatment-naïve or previously treated advanced NSCLC. Patients received 2 mg/kg IV of KEYTRUDA every three weeks or 10 mg/kg IV of KEYTRUDA every two weeks or every three weeks. The primary endpoint was overall response rate (ORR) and secondary endpoints included progression-free survival (PFS) and OS.

At the study’s previously reported primary analysis, KEYNOTE-001 showed that KEYTRUDA demonstrated an ORR of 41% in patients with a TPS ≥50%; all responses were partial responses (95% CI, 29-54). Of the patients who responded, 84% continued to respond to treatment with KEYTRUDA, including 11 patients with ongoing responses of six months or longer.

Study design and additional data from KEYNOTE-010

Ten-year outcomes for KEYTRUDA were measured in the Phase 2/3 KEYNOTE-010 trial (ClinicalTrials.gov; NCT01905657), which evaluated patients with metastatic NSCLC whose tumors expressed PD-L1 (TPS ≥1%) that had progressed after platinum-containing chemotherapy and, if appropriate, targeted therapy for EGFR or ALK genomic tumor aberrations. The trial enrolled 1,033 patients who were randomized (1:1:1) to receive 2 mg/kg IV or 10 mg/kg IV of KEYTRUDA every three weeks or chemotherapy (docetaxel) every three weeks. The primary endpoints for this trial were OS and PFS, and secondary endpoints included ORR and duration of response (DOR).

At the study’s previously reported primary analysis, KEYNOTE-010 showed that 2 mg/kg of KEYTRUDA reduced the risk of death by 29% (HR=0.71 [95% CI, 0.58-0.88]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of death by 39% (HR=0.61 [95% CI, 0.49-0.75]; p<0.001) in patients with a TPS ≥1% versus chemotherapy. Two mg/kg of KEYTRUDA reduced the risk of disease progression or death by 12% (HR=0.88 [95% CI, 0.73-1.04]; p=0.068) and 10 mg/kg of KEYTRUDA reduced the risk of disease progression or death by 21% (HR=0.79 [95% CI, 0.66-0.94]; p=0.005) in patients with a TPS ≥1% versus chemotherapy. Additionally, the analysis showed that 2 mg/kg of KEYTRUDA reduced the risk of death by 46% (HR=0.54 [95% CI, 0.38-0.77]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of death by 50% (HR=0.50 [95% CI, 0.36-0.70]; p<0.001) in patients with a TPS ≥50% versus chemotherapy. Two mg/kg of KEYTRUDA reduced the risk of disease progression or death by 42% (HR=0.58 [95% CI, 0.43-0.77]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of disease progression or death by 41% (HR=0.59 [95% CI, 0.45-0.78]; p<0.001) in patients with a TPS ≥50% versus chemotherapy.

Study design and additional data from KEYNOTE-024

Eight-year outcomes for KEYTRUDA were measured in the Phase 3 KEYNOTE-024 trial (ClinicalTrials.gov; NCT02142738), which evaluated patients with previously untreated metastatic NSCLC whose tumors express high levels of PD-L1 (TPS ≥50%) with no EGFR or ALK genomic tumor aberrations. The trial enrolled 305 patients who were randomized (1:1) to receive 200 mg of KEYTRUDA every three weeks or platinum-based chemotherapy. The primary endpoint for this trial was PFS, and secondary endpoints included OS and ORR. In this study, 10.3% (209) of patients transitioned to KEYNOTE-587.

At the study’s previously reported primary analysis, KEYNOTE-024 showed that KEYTRUDA reduced the risk of disease progression or death by 50% (HR=0.50 [95% CI, 0.37-0.68]; p<0.001) versus chemotherapy. Additionally, KEYTRUDA reduced the risk of death by 40% (HR=0.60 [95% CI, 0.41-0.89]; p=0.005) versus chemotherapy.

Study design and additional data from KEYNOTE-042

Eight-year outcomes for KEYTRUDA were measured in the Phase 3 KEYNOTE-042 trial (ClinicalTrials.gov; NCT02220894), which evaluated patients with stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors expressed PD-L1 (TPS ≥1%) and who had not received prior systemic treatment for metastatic NSCLC. The trial enrolled 1,251 patients who were randomized (1:1) to receive 200 mg of KEYTRUDA every three weeks or platinum-based chemotherapy. The primary endpoint for this trial was OS in patients with a TPS ≥50%, ≥20% or ≥1% and secondary endpoints included PFS and ORR as assessed by blinded independent central review (BICR) according to RECIST v1.1 in patients with a TPS ≥50%, ≥20% or ≥1%. In this study, 4.4% (50) of patients transitioned to KEYNOTE-587.

At the study’s previously reported primary analysis, KEYNOTE-042 showed that KEYTRUDA reduced the risk of death by 31% (HR=0.69 [95% CI, 0.56-0.85]; p=0.0006) in patients with a TPS ≥50% and by 19% (HR=0.81 [95% CI, 0.71-0.93]; p=0.0036) in patients with a TPS ≥1% versus chemotherapy. Median OS was 20.0 months (95% CI, 15.4-24.9) for KEYTRUDA in patients with a TPS ≥50% versus 12.2 months (95% CI, 10.4-14.2) for chemotherapy, and 16.7 months (95% CI, 13.9-19.7) for KEYTRUDA in patients with a TPS ≥1% versus 12.1 months (95% CI, 11.3-13.3) for chemotherapy.

About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2025, the overall five-year survival rate for patients diagnosed with lung cancer was 27% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.

On October 20, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress held in Berlin, Germany, Results from a Phase 3 study of the Company’s human epidermal growth factor receptor 2 (HER2)-directed ADC trastuzumab botidotin (also known as A166) trastuzumab botidotin versus trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic BC was presented as an oral report by Professor Xichun Hu from Fudan University Shanghai Cancer Center (Presentation # LBA24, Proffered paper session 1: Breast cancer, metastatic).

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Trastuzumab botidotin is a HER2-targeted ADC composed of a cytotoxic drug (Duostatin-5, anti-microtubule agent) with site-specific conjugation to trastuzumab via a stable protease-cleavable valine-citrulline linker. The unique linker is stable in plasma and selectively cleaved by lysosomal cathepsin B that is up-regulated in cancer cells.

In this study, a total of 365 patients with HER2+ unresectable or metastatic BC who had received at least one prior anti-HER2 therapy were randomized (1:1) to receive trastuzumab botidotin or T-DM1. 53% of patients had received ≥2 lines of anti-HER2 therapy, 61% of patients had HER2 Immunohistochemistry (IHC) 3+, and 60% of patients had been treated with TKIs, particularly pyrotinib (56%). As of April 26, 2025, median follow-up was 14.9 months.

Median PFS was significantly longer in trastuzumab botidotin than in T-DM1 (11.1 months vs 4.4 months; HR: 0.39, 95% CI, 0.30-0.51, p<0.0001). PFS benefit with trastuzumab botidotin was consistently observed regardless of prior lines of anti-HER2 therapy (HR 0.36, 95% CI, 0.25-0.53, for 1 prior line; HR 0.39, 95% CI, 0.28-0.56, for ≥2 prior lines).

ORR by blinded independent central review (BICR) was 76.9% vs 53.0%.

A trend toward benefit in OS was observed in trastuzumab botidotin (HR 0.62; 95% CI, 0.38-1.03).

Grade ≥3 treatment emergent adverse events (TEAEs) occurred in 69.8% of patients in trastuzumab botidotin and 63.7% in T-DM1. The most common TEAEs associated with dose reduction were ocular AEs for trastuzumab botidotin, and were platelet count decreased for trastuzumab emtansine. Only two patients permanently discontinued trastuzumab botidotin due to TEAE. No on-treatment deaths were observed in trastuzumab botidotin, compared with 1.6% in T-DM1, all of which were considered unrelated to treatment.

As a conclusion, this second head-to-head trial comparing T-DM1 with other anti-HER2 regimens demonstrated that trastuzumab botidotin statistically improved PFS with an ORR of 76.9% vs 53.0%. PFS benefit with trastuzumab botidotin was consistently observed regardless of prior lines of anti-HER2 therapy. Ocular AEs were also manageable.

"Professor Xichun Hu, National Lead Principal Investigator from Fudan University Shanghai Cancer Center:"Trastuzumab botidotin effectively balances safety and efficacy through its unique molecular design, reducing the incidence of interstitial lung disease and hematologic toxicity. According to research data, trastuzumab botidotin demonstrated significant survival benefits in the pivotal Phase III trial, with an overall manageable safety profile, providing a new important treatment option for pretreated HER2+ BC patients. These positive results also offer robust evidence-based support for personalized treatment and updates to clinical practice guidelines."

About Trastuzumab botidotin

Trastuzumab botidotin is a differentiated HER2 ADC to treat advanced HER2+ solid tumors. As an innovative HER2 ADC developed by the Company, it conjugates a novel, monomethyl auristatin F (MMAF) derivative (a highly cytotoxic tubulin inhibitor, Duo-5) via a stable, enzyme-cleavable linker to a HER2 monoclonal antibody with a DAR of 2. Trastuzumab botidotin specifically binds to HER2 on the surface of tumor cells and is internalized by tumor cells, releasing the toxin molecule Duo-5 inside the cell. Duo-5 induces tumor cell cycle arrest in the G2/M phase, leading to tumor cell apoptosis. After targeting HER2, trastuzumab botidotin can also inhibit the HER2 signaling pathway; it has antibody-dependent cell-mediated cytotoxicity (ADCC) activity.

Based on the results of a multi-center, randomized, open-label, controlled, Phase 3 KL166-III-06 study, trastuzumab botidotin was approved for marketing by the NMPA in for adult patients with unresectable or metastatic HER2 positive BC who have received one or more prior anti-HER2 therapy. At a pre-specified interim analysis, trastuzumab botidotin demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of PFS as assessed by the BICR compared with T-DM1[; the beneficial trend for OS of trastuzumab botidotin was also observed.

Currently, the Company has initiated an open, multi-center Phase 2 clinical study of trastuzumab botidotin in the treatment of HER2+ unresectable or metastatic BC that previously received a topoisomerase inhibitor ADC.

(Press release, Kelun, OCT 20, 2025, View Source [SID1234656834])

On October 20, 2025 Iksuda Therapeutics (Iksuda), the developer of class leading, antibody drug conjugates (ADCs), reported the presentation of new data from its Phase 1 study of IKS014, a human epidermal growth factor receptor 2 (HER2)-directed ADC, in patients with advanced HER2+ solid tumours. The data was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Berlin, Germany.

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The Phase 1 study (NCT05872295) is a non-randomised, open-label, multicentre trial evaluating IKS014 in patients with locally advanced or metastatic solid tumours that express HER2. Part I, the dose escalation portion, is being conducted in sites in Australia and is designed to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) for IKS014 and provide initial safety, tolerability, efficacy, pharmacokinetic, pharmacodynamic and immunogenicity characteristics. Part II dose expansion studies will assess IKS014 in HER2+ breast cancer in patients who have previously received Enhertu, HER2-low breast cancer, HER2+-gastric/ GEJ cancers and other HER2+ tumours and mutated HER2-NSCLC. Dose expansion studies will be conducted in sites in the US, Australia, New Zealand and Singapore.

At the data cut-off date (31 July 2025), a total of 62 patients were enrolled in the study, with 55 patients evaluable for efficacy as measured by Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Anti-tumour activity was observed across all dose levels, with partial responses and unconfirmed partial responses observed in various tumour indications including breast, lung, oesophageal, ovarian, gastric, gallbladder and gastroesophageal junction cancers and in both HER2+ and HER2-low tumours.

Amongst 11 participants with breast cancer treated at doses >90mg/m2, seven responses were seen (objective response rate (ORR) 64%), including partial responses in all four patients with HER2+ disease. Three of these patients had previously received Enhertu. Additionally, amongst 10 patients with pre-treated, HER2+ oesophageal cancer that were enrolled across all dose levels, five achieved a response, including complete regression in one patient with non-measurable disease.

Treatment with IKS014 was generally well-tolerated at doses up to 120mg/m2 (~3.2 mg/kg), with anticipated adverse events including ocular surface AEs, pneumonitis and hypokalaemia, all of which were predominately Grade 1 and Grade 2.

An MTD was not reached per the study protocol. Dose selection for further evaluation in the expansion cohorts will be based on preliminary activity, safety, pharmacokinetic, pharmacodynamic profile and overall benefit-risk assessment from the dose escalation. The Phase 1 trial is expected to complete in H2 2026.

This data follows positive data from Phase 1 clinical trials through Fosun Pharma, which is now progressing FS-1502 (IKS014) through Phase 3 trials in China.1

Dr. Dave Simpson, Chief Executive Officer, Iksuda Therapeutics, commented: "We are hugely encouraged by these data, which illustrates the potential of IKS014 to improve outcomes and address the clinical unmet need across various HER-2 positive cancers, including treatment of those patients which are refractory to prior therapy options."

About IKS014

IKS014 is a potential best-in-class antibody drug conjugate, benefiting from tumour selective activation and release of the cytotoxic agent monomethyl auristatin F (MMAF). In preclinical trials, it displayed impressive activity in high- and low-HER2 expressing tumours with a favourable Therapeutic Index compared with other HER2-directed drugs. Iksuda gained exclusive world-wide rights (excluding Greater China and South Korea) to IKS014 from LigaChem Biosciences (View Source).

(Press release, Iksuda Therapeutics, OCT 20, 2025, View Source [SID1234656850])

On October 20, 2025 Redhill Biopharma, a specialty biopharmaceutical company, reported the signing of a strategic partnership with Cumberland Pharmaceuticals Inc. (Nasdaq: CPIX) ("Cumberland"), a specialty pharmaceuticals company with a strong gastrointestinal market presence, whereby Cumberland will invest $4 million for a 30% ownership stake in RedHill’s global Talicia business. The companies will share in the financial performance and operational support for the Talicia brand with RedHill retaining 70% ownership and joint control. All other aspects of RedHill’s business remain unchanged.

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RedHill and Cumberland have also entered into a U.S. Talicia co-commercialization agreement with an equal sharing of the product’s net revenues. Cumberland commits to significant additional investment to support Talicia’s U.S. business, providing the strength of its national sales force to feature and further enhance the brand’s marketing and promotional activities. The partnership is designed to deliver economies of scale and cost reductions through shared responsibility for Talicia’s U.S. sales, marketing, manufacturing, supply, regulatory and administrative operations.

"This strategic partnership provides an excellent growth opportunity for RedHill and for Cumberland, a highly capable and driven partner with a strong gastroenterology market presence, adding a market-leading approved product to its portfolio. We believe Cumberland can help drive prescriptions and deliver revenue growth, further strengthening Talicia’s U.S. market leadership," said Dror Ben-Asher, RedHill’s CEO. "The transaction highlights the significant standalone value and commercial strength of the Talicia business, and positions RedHill to accelerate growth, reinforce its financial position and reduce costs, while continuing to advance our broader strategic objectives."

"Talicia has an outstanding product profile and represents an excellent strategic fit for Cumberland, providing us with an important growth opportunity," said A.J. Kazimi, Cumberland’s CEO. "These arrangements with RedHill provide us with the only FDA-approved all-in-one, low-dose rifabutin-based therapy to address H. pylori antibiotic resistance in support of patient care. We can build on the excellent foundation RedHill has created for the product, representing a strong growth opportunity for both companies, and we are delighted to be working with them to pursue this potential."

"There is a real problem with H. pylori antibiotic resistance, with eradication treatment failure rates of up to 40% associated with clarithromycin-containing therapies3. Leading U.S. H. pylori treatment guidelines are explicit on the need to avoid using clarithromycin as part of any H. pylori treatment regimen without prior susceptibility testing," said Rick Scruggs, RedHill’s Chief Commercial Officer. "Moreover, H. pylori is a key risk factor for gastric cancer, a cause of approximately 11,000 U.S. deaths4 a year. This is despite it being reported that eradication of H. pylori can lead to a 75% decreased gastric cancer risk.5 The need for effective H. pylori treatment designed to address antibiotic resistance is clear."

The transaction also supports RedHill’s plan to regain compliance with Nasdaq’s minimum stockholders’ equity requirement and maintain its continued listing, supporting access to capital and long-term financial stability. Accordingly, as a result of this transaction, as of the date of this press release, the Company believes it has stockholder’s equity in excess of the $2.5 million requirement for continued listing pursuant to Nasdaq Listing Rule 5550(b)(1). The Company intends to notify Nasdaq of its compliance status so that Nasdaq can make a determination as to whether the Company has regained compliance with all applicable requirements for continued listing on The Nasdaq Capital Market. However, there can be no assurance that Nasdaq will determine that the Company has regained compliance with the Nasdaq continued listing standards.

RedHill is committed to expanding patient access to Talicia globally. This month we announced the licensing of Talicia for new Middle East markets in a deal worth potentially $1.8 million plus sales royalty payments, with efforts to further broaden market access and secure additional non-dilutive ex-U.S. licensing revenue streams ongoing.

Talicia is patent protected through 2042 and received eight years of U.S. market exclusivity under its Qualified Infectious Disease Product (QIDP) designation.

About H. pylori

H. pylori is a bacterial infection that affects approximately 35% of the U.S. adult population6 (an estimated 1.6 million U.S. patients are treated annually) rising to more than 50% globally7. Classified by the World Health Organization (WHO) as a Group 1 carcinogen, H. pylori is the strongest known risk factor for gastric cancer (between 70% to 90% of cases with more than 27,000 Americans diagnosed with gastric cancer annually8 and approximately 800,000 deaths globally per year), a major risk factor for peptic ulcer disease (90% of cases)9 and gastric mucosa-associated lymphoid tissue (MALT) lymphoma10. Eradication of H. pylori is becoming increasingly difficult, with current therapies failing in approximately 25-40% of patients who remain H. pylori-positive due to high resistance of H. pylori to antibiotics, especially clarithromycin, which is still commonly used in standard combination therapies11.

About Talicia

Approved by the FDA for the treatment of H. pylori infection in adults in November 2019, Talicia is a novel, fixed-dose, all-in-one oral capsule combination of two antibiotics (amoxicillin and rifabutin) and a proton pump inhibitor (omeprazole). Talicia received eight years of U.S. market exclusivity under its Qualified Infectious Disease Product (QIDP) designation and is also covered by U.S. patents extending patent protection through 2042 with additional patents and applications pending and granted in various territories worldwide. Talicia is also approved by the United Arab Emirates (UAE) Ministry of Health.

(Press release, RedHill Biopharma, OCT 20, 2025, View Source [SID1234656819])

On October 20, 2025 GlycoNex, Inc. (4168, hereinafter referred to as GNX), a clinical stage biotechnology company focused on the development of glycan-directed cancer immunotherapies, reported that an abstract describing preclinical research on its first-in-class antibody-drug conjugate (ADC), GNX1021, has been accepted for presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place October 22–26, 2025, in Boston, Massachusetts.

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The abstract, titled "Targeting branched Lewis B/Y glycans with GNX1021: A novel ADC approach for HER2-low gastric cancer," describes preclinical work characterizing GNX1021’s novel glycan-targeting mechanism. GNX1021 is engineered to recognize branched Lewis B/Y, a tumor-associated glycan highly expressed in gastric and other epithelial tumors but with limited expression in healthy tissue, potentially enabling a new level of tumor selectivity.

GlycoNex anticipates submitting an Investigational New Drug (IND) application in the first quarter of 2026 for a first-in-human clinical trial of GNX1021. The program builds on GlycoNex’s proprietary GlycoSH antibody bank and extensive expertise in glycan-directed antibody and ADC development.

Presentation Details:

Event:

American Association for Cancer Research (AACR) (Free AACR Whitepaper) NCI-EORTC
International Conference on Molecular Targets and Cancer Therapeutics
2025

Session:

Poster Session B

Abstract Title:

Targeting branched Lewis B/Y glycans with GNX1021: A novel ADC
approach for HER2-low gastric cancer

Date and Time:

Friday, October 24, 12:30-4:00 pm

Location:

Hynes Convention Center, Boston; Level 2, Exhibit Hall D

(Press release, GlycoNet, OCT 20, 2025, View Source [SID1234656835])