lunbotinib (EP0031) / Sichuan Kelun Pharma, Ellipses Pharma - LARVOL DELTA

Efficacy and safety of lunbotinib (A400/EP0031), a next-generation selective RET inhibitor (SRI), from a pivotal phase II study in patients with advanced RET fusion–positive non–small cell lung cancer (NSCLC). (ASCO 2026) - P1/2 | "Lunbotinib demonstrated robust efficacy in pts with advanced RET-fusion positive NSCLC, with high ORR and prolonged PFS in both pre-treated and treatment-naïve populations, and notable intracranial activity. Safety profile was manageable, with no new signals identified. These data support the potential of lunbotinib as a valuable therapeutic option for this population."

Clinical • IO biomarker • Metastases • P2 data • Dry Eye Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ophthalmology • Solid Tumor • RET

A phase I study of KL590586, a next-generation selective RET inhibitor, in patients with RET-altered solid tumors. (ASCO 2023) - P1/2 | "KL590586 was well-tolerated, and associated with robust clinical activity in RET-altered tumors regardless of tumor type, including NSCLC pts with resistance to1st gen SRIs and with CNS mets. Pivotal studies are planned. Clinical trial information: NCT05265091."

Clinical • IO biomarker • P1 data • Cardiovascular • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pain • Pancreatic Cancer • Solid Tumor

EP0031-101: A Study of EP0031 (Lunbotinib) in Patients With Advanced RET-altered Malignancies (clinicaltrials.gov) - P1/2 | N=265 | Recruiting | Sponsor: Ellipses Pharma | Trial completion date: Jun 2027 ➔ Mar 2028 | Trial primary completion date: Dec 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Study 2: Efficacy and safety of lunbotinib (A400/EP0031), a next-generation selective RET inhibitor (SRI), from a pivotal phase Ⅱ study in patients with advanced RET-fusion positive non-small cell lung cancer (NSCLC) (PRNewswire) - "Kelun-Biotech to Present...in the Oral Presentation Session on Non-Small Cell Lung Cancer at ASCO 2026....As of October 29, 2025, 71 patients with prior platinum-based chemotherapy and immunotherapy (pre-treated patients) and 92 patients who had not received prior systemic therapy (treatment-naïve patients) were enrolled....The study demonstrated that: (i) Independent Review Committee (IRC)-assessed confirmed ORR was 87.1% (95% CI: 77.0-93.9) in pre-treated patients and 81.3% (95% CI: 71.8-88.7) in treatment-naïve patients; (ii) Median PFS was 27.5 months in pre-treated patients (immature) and NR in treatment-naïve patients, with 24-month PFS rates of 52.1% and 59.9%, respectively; (iii) Median OS was not reached in either group, with 24-month OS rates of 65.7% in pre-treated patients and 74.1% in treatment-naïve patients."

P2 data • Non Small Cell Lung Cancer

Kelun-Biotech Announces Three Clinical Study Results Selected for Oral Presentations at 2026 ASCO Annual Meeting (Businesswire) - "In this meeting, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (6990.HK) will present results from three clinical studies, including data from its TROP2 ADC sacituzumab tirumotecan (sac-TMT, next-generation selective RET inhibitor lunbotinib fumarate (A400/EP0031) and novel ADC SKB500."

P1 data • P2 data • P3 data • Non Small Cell Lung Cancer

A phase I/II study to evaluate EP0031 (lunbotinib), a next-generation selective RET inhibitor, as monotherapy and in combination with chemotherapy, in patients with advanced RET-fusion-positive NSCLC (AACR 2026) - P1/2 | "There is growing evidence that RET fusion-positive NSCLC is sensitive to pemetrexed-based chemotherapy and preclinical evidence confirms strong synergy between EP0031 and chemotherapy. Alonso G, et al. J Clin Oncol 2025: 43:16_suppl, 8598"

Clinical • Combination therapy • Metastases • Monotherapy • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Evaluation of the next-generation selective RET inhibitor EP0031/A400 (lunbotinib) +/- standard of care NSCLC chemotherapy regimens in preclinical models of RET-aberrated cancers (ELCC 2026) - P1/2 | "In cell viability assays LC-2/ad and TPC1 cells showed various degrees of sensitivity to cisplatin/carboplatin, pemetrexed and paclitaxel/docetaxel. In LC-2/ad cells, synergy was also observed with taxanes.Conclusions The unexpected synergy observed for EP0031 + SoC chemotherapy in vitro and the challenge of tumour heterogeneity, provides a strong rationale for evaluating this combination in the clinic. A trial of EP0031 + platinum/pemetrexed is ongoing in patients with RET-fusion positive NSCLC naïve to or previously treated with first-gen SRI (NCT05443126)."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCDC6 • RET

A phase I/II study of EP0031 (lunbotinib), a next-generation selective RET inhibitor, as monotherapy and in combination with chemotherapy, in advanced RET fusion-positive NSCLC (ELCC 2026) - P1/2 | "There is growing evidence that RET fusion-positive NSCLC is sensitive to pemetrexed-based chemotherapy and preclinical evidence confirms strong synergy between EP0031 and chemotherapy. Circulating tumour DNA is collected to evaluate the emergence of on- and off-target mutations. The study is recruiting across the US, Europe, and the UAE."

Combination therapy • Metastases • Monotherapy • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • RET

A phase I/II study to evaluate EP0031 (lunbotinib), a next generation selective RET inhibitor, as monotherapy and in combination with chemotherapy, in patients with advanced RET fusion positive NSCLC (BTOG 2026) - "Preclinical evidence indicates strong synergy between EP0031 and chemotherapy. In RET fusion-positive NSCLC, the combination of SRI with chemotherapymay therefore represent a promising strategy to overcome resistance and improve outcomes."

Clinical • Combination therapy • Metastases • Monotherapy • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • RET

A Study of KL590586 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=414 | Active, not recruiting | Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Trial completion date: May 2025 ➔ Dec 2026 | Trial primary completion date: May 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Biliary Tract Cancer • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor

Commercialization Accelerates: Sales & Market Access Expanding Footprint (PRNewswire) - "Sac- TMT, tagitanlimab and Cetuximab N01 have been successively launched, marking the full-scale initiation of commercialization. The Company expects to launch trastuzumab botidotin in the China market and file one NDA for A400 in the second half of 2025."

China filing • Launch non-US • Colorectal Cancer • HER2 Positive Breast Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

Kelun-Biotech's New Drug Application for Its Novel Next-generation Selective RET Inhibitor A400/EP0031 Accepted for Review by the NMPA for the Treatment of RET-fusion positive NSCLC (PRNewswire) - "This acceptance for review is based on the positive results from the two pivotal Phase 2 cohorts of the KL400-I/II-01 study for both 1L and 2L+ advanced RET-fusion positive NSCLC."

China filing • Non Small Cell Lung Cancer

Final results of a phase 1 study of EP0031, a next generation selective RET inhibitor (SRI) in patients with SRI naïve or pretreated advanced RET-altered tumors. (ASCO 2025) - P1/2 | "There is a need for new treatments for pts that progress on 1st gen SRIs. EP0031 was associated with durable responses in advanced RET altered solid tumors previously treated with SRI, including pts with brain mets, with a manageable safety profile. These data confirm that the first in class next gen SRI EP0031 has the potential to address a high unmet need."

Clinical • Metastases • P1 data • Anemia • Constipation • Endocrine Cancer • Fatigue • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hypertension • Keratitis • Lung Cancer • Metabolic Disorders • Nephrology • Non Small Cell Lung Cancer • Ocular Inflammation • Oncology • Ophthalmology • Pain • Pancreatic Cancer • Pulmonary Disease • Renal Disease • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma • Xerostomia • RET

Results from a Phase 1 study of KL590586 in patients with advanced RET-mutant medullary thyroid cancer (MTC) (The Manila Times) - P1/2 | N=414 | NCT05265091 | Sposnor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | "As of September 20, 2024, the confirmed ORR was 63.0% and the DCR was 100% for overall population. The confirmed ORR was 56.3% (9/16) and 62.5% (5/8) in patients with prior multikinase inhibitor (MKI) or treatment naïve, respectively. Median DoR was not reached, with the longest duration still ongoing at 25.8 months. Similarly, median PFS was not reached, with the 24-month PFS rate of 77.8%. All patients experienced TRAEs, with grade ≥3 TRAEs occurred in 22.2% of patients. No TRAEs led to treatment discontinuation or death."

P1 data • Thyroid Gland Medullary Carcinoma

Kelun-Biotech to Present Results of Six Clinical Studies at 2025 ASCO Annual Meeting (PRNewswire) - "Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd...announced that it will present results from six Kelun-led clinical studies at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago from May 30 to June 3. Results include data from its TROP2 antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT), anti-PD-L1 mAb tagitanlimab, and RET inhibitor KL590586 (A400/EP0031). The abstracts for these studies will be published on the ASCO's official website on May 22, 2025, local time."

Clinical data • Lung Non-Squamous Non-Small Cell Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Thyroid Gland Carcinoma • Triple Negative Breast Cancer

Ellipses Launches Pioneering Clinical Trial Programme in Middle East (Businesswire) - "Ellipses Pharma Limited...announced today it has inaugurated the first large-scale Phase 1/2 oncology clinical study of its kind in the United Arab Emirates, marking a significant milestone in the region’s healthcare landscape. Following approval by the UAE regulators and the Ministry and Department of Health, this study will be conducted initially at two major healthcare centres in Abu Dhabi - the Cleveland Clinic and Tawam Hospital. The inclusion of a third study centre is pending. Patient recruitment has commenced. The trial will focus on Ellipses' next generation selective RET inhibitor (SRI), EP0031/A400, a potential treatment of RET-altered tumours, most prevalent in non-small cell lung cancer and thyroid cancer."

Trial status • Non Small Cell Lung Cancer

EP0031 a next-generation selective RET inhibitor (SRI): Correlation of molecular and clinical responses in patients with RET alteration positive solid tumours naïve to or following prior SRI (ESMO 2024) - P1/2 | "There was encouraging evidence of clinical responses across the pt population, including pts naïve to or who had received prior SRI. Methylation-based ctDNA MR appears to show a strong correlation with the best clinical response. MR appears to be an early indicator of clinical response."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Kelun Biotech-B (06990), a leading biotech in the ADC field, joins hands with Merck to expand its global presence [Google translation] (Sina Corp) - "Kelun Biotech is a world-leading ADC Biotech, and joins hands with Merck to expand its global presence...A167 (PD-L1 monoclonal antibody) is expected to be approved for nasopharyngeal carcinoma in the second half of 2024. A400 (RET inhibitor) is expected to submit a marketing application in 2024."

Approval • Filing • Licensing / partnership • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

A Study of KL590586 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=414 | Active, not recruiting | Sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Metastases • Biliary Tract Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase-1 dose escalation and expansion study of EP0031, a next-generation selective RET inhibitor (SRI), in patients with SRI-naïve or pretreated advanced RET-altered NSCLC and other tumors. (ASCO 2024) - P1/2 | "These data add significantly to the large clinical data set reported for EP0031 from a trial of over 130 patients in China, most with advanced RET fusion +ve NSCLC. EP0031 has a manageable toxicity profile with promising activity in advanced NSCLC previously treated with or naïve to SRI, including those with brain metastases. This study is continuing at pace with Phase 2 expansion cohorts in SRI pre-treated and naïve patients."

Clinical • Metastases • P1 data • Anemia • Cardiovascular • Constipation • Endocrine Cancer • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Pancreatic Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma • RET

Ellipses' next generation selective RET inhibitor EP0031/A400 cleared to start Phase 2 (PRNewswire) - "Ellipses Pharma Limited...announced today the U.S. Food and Drug Administration (FDA) has confirmed the company's next generation selective RET inhibitor (SRI), EP0031/A400, is clear to progress into Phase 2 clinical development...The latest clinical data from the Ellipses Phase 1 study will be presented at ASCO in Chicago on June 3rd 2024."

P1 data • Trial status • Non Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

Ellipses' next generation selective RET inhibitor EP0031/A400 granted Fast Track designation by US Food and Drug Administration (Yahoo Finance) - "Ellipses Pharma...announced today that it has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for its next generation selective RET inhibitor EP0031/A400 for the potential treatment of RET-fusion positive Non-Small Cell Lung Cancer (NSCLC)....Data from the ongoing modular interventional phase 1/2 trial, which aims to assess the safety, side effects and effectiveness of EP0031/A400 in patients with advanced RET-altered malignancies, were submitted in support of the application, where for the first time EP0031/A400 showed tumour responses in NSCLC patients who were previously treated with first-generation SRIs."

Fast track designation • Non Small Cell Lung Cancer

A Study of EP0031-101 in Patients With Advanced RET-altered Malignancies (clinicaltrials.gov) - P1/2 | N=265 | Recruiting | Sponsor: Ellipses Pharma

Metastases • Trial completion date • Trial primary completion date • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Orphan Designation: Treatment of tissue-agnostic RET fusion-positive solid tumors (FDA) - Date Designated: 11/15/2023

Orphan drug • Oncology • Solid Tumor

Preliminary results from a phase I/II study evaluating the safety, tolerability, and efficacy of EP0031, a next generation selective RET inhibitor, in patients with advanced RET-altered malignancies. (AACR-NCI-EORTC 2023) - No abstract available

Clinical • Metastases • P1/2 data • Oncology