Fruquintinib: further analyses from the FRESCO-2 study and exploratory combination studies
Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptor (“VEGFR”)-1, -2 and -3.1 Fruquintinib has been generally well tolerated in patients to date and is being investigated as a single agent and in combination with other anti-cancer therapies. 13 presentations and publications, including several investigator-initiated-trials (“IITs”), are listed in the table below.
Additional FRESCO-2 analyses: New analyses from the FRESCO-2 multi-regional clinical trial (MRCT) are being presented. FRESCO-2 is a key study supporting ongoing and upcoming submissions to the
CRC real-world data: Results from a prospective, 3,005-patient Phase IV study to evaluate the safety of fruquintinib in real-world clinical practice in
PD-1 combination in ccRCC: PFS results from an exploratory study of the fruquintinib and sintilimab (an anti-programmed cell death protein-1 [“PD-1”] antibody) combination in metastatic clear cell renal cell carcinoma (“ccRCC”) are available with longer term follow-up. At data cut-off on
IIT in 2L MSS CRC: A number of IITs are being presented, including initial results of an IIT for fruquintinib in combination with investigator's choice of chemotherapy in second-line metastatic CRC with microsatellite-stable (MSS) phenotype. At median follow up of 8.4 months, median PFS was not reached in 31 efficacy evaluable patients, disease control rate (DCR) was 90.3% and objective response rate (ORR) was 48.4%. Five patients received reduced doses of fruquintinib.
Surufatinib: exploratory results in combination with other agents
Surufatinib is a small-molecule inhibitor of VEGFR-1, -2 and -3, fibroblast growth factor receptor (“FGFR”)-1 and colony-stimulating factor 1 receptor (CSF-1R). Seven related presentations and publications, including IITs, are listed in the table below.
PD-1 combinations: We conducted an open-label, multi-cohort, single-arm Phase II study of surufatinib plus toripalimab (an anti-PD-1 antibody) in several advanced solid tumors. We reported the results from the advanced thyroid cancer and endometrial cancer cohorts (NCT04169672). Amongst efficacy evaluable radioactive iodine-refractory differentiated thyroid cancer patients, median PFS was 10.9 months and median OS was not reached (median follow-up duration was 22.1 months). Amongst efficacy evaluable endometrial cancer patients, median PFS was 5.4 months and 12-month OS rate was 71.0% (median follow-up duration was 16.8 months). In both cohorts, the combination showed a tolerable safety profile.
Combo IITs: A number of IITs are being presented for surufatinib in combination with other agents, including with chemotherapy as well as with camrelizumab (an anti-PD-1 antibody) plus different chemotherapy regimens.
Preliminary results in an ongoing IIT in treatment of patients with naïve metastatic pancreatic adenocarcinoma (PDAC) showed median PFS of 8.8 months in patients who received a combination of surufatinib, camrelizumab, nab-paclitaxel and S-1, compared to 5.8 months in patients who received gemcitabine in combination with nab-paclitaxel. Markers of immune cells were observed in an analysis of tissue samples from 13 (out of 20) patients who received S-1 in combination with surufatinib, camrelizumab and nab-paclitaxel. The combination safety profiles were manageable.
The IIT in previously treated CRC study completed the dose escalation phase of the study in 12 patients and enrolled a further 36 patients in the dose expansion phase of the study. The investigators found the combination of surufatinib with camrelizumab, irinotecan and GM-CSF to be well tolerated with a manageable safety profile. Median PFS was 7.2 months (95% CI 3.7-10.7).
The IIT in previously treated, advanced driver-gene negative, non-squamous, non-small cell lung cancer (“NSCLC”) in combination with chemotherapy. This study complements Phase II results previously presented for the surufatinib and toripalimab combination in patients with treatment naïve advanced NSCLC with positive PD-L1 expression.
HMPL-453: first in human results
FGFRs regulate numerous cellular processes. Dysregulation of FGFR signaling due to receptor fusion, mutation or amplification is observed across multiple cancer types, making activated FGFRs an important therapeutic target. HMPL-453 is a highly potent and selective inhibitor of FGFR-1, -2, and -3. Preclinical data presented at the
Here we present first-in-human data for HMPL-453 in patients with previously treated advanced intrahepatic cholangiocarcinoma (IHCC) harboring FGFR2 fusions. A Phase II registration intent cohort is currently enrolling such patients (NCT04353375).
Further details including the full abstracts are available at meetings.asco.org, as summarized below.
ABSTRACT PRESENTATION DETAILS
Abstract title | Presenter / Lead author | Presentation details |
FRUQUINTINIB | ||
Subgroup analyses of safety and efficacy by number and types of prior lines of treatment in FRESCO-2, a global phase III study of fruquintinib in patients with refractory metastatic colorectal cancer | Abstract # 3604 Poster Session Gastrointestinal Cancer–Colorectal and Anal | |
Analysis of fruquintinib adverse events of special interest from phase 3 of the FRESCO-2 study | Abstract # 3601 Poster Session Gastrointestinal Cancer–Colorectal and Anal | |
A phase IV study to evaluate the safety of fruquintinib in Chinese real-world clinical practice | Abstract # e15568 Publication Only Gastrointestinal Cancer–Colorectal and Anal | |
Fruquintinib plus sintilimab in patients with either treatment-naive or previously first line treated metastatic clear-cell renal cell carcinoma (ccRCC): Results from a multicenter, single-arm phase 2 study | Abstract # e16514 Publication Only Genitourinary Cancer—Kidney and Bladder | |
Efficacy and safety of fruquintinib plus investigator's choice of chemotherapy as second-line therapy in metastatic colorectal cancer: A multicenter, single-arm phase 2 trial | Abstract # 3582 Poster Session Gastrointestinal Cancer–Colorectal and Anal | |
Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric adenocarcinoma (FRUTINEOGA): a multicenter, phase II study. | Liucheng Wu, | Abstract # e16063 Publication Only Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary |
Association of neutrophil/lymphocyte ratio and IFN-γ with clinical response and survival in patients with MSS/pMMR mCRC treated with anti-PD-1 and VEGF inhibitors | Abstract # e14610 Publication Only Developmental Therapeutics—Immunotherapy | |
Efficacy and safety of radiation therapy combined with anti-angiogenic agents and immunotherapy for MSS/pMMR metastatic colorectal cancer: A real-world study | Abstract # e15559 Publication Only Gastrointestinal Cancer—Colorectal and Anal | |
A phase II study of fruquintinib in the first- (1L) or second-line (2L) treatment of unresectable metastatic soft tissue sarcoma | Abstract # e23547 Publication Only Sarcoma | |
Quality of life, effectiveness, and compliance of fruquintinib in the treatment of metastatic colorectal cancer: Results from a prospective real-world study. | Abstract # e15557 Publication Only Gastrointestinal Cancer–Colorectal and Anal | |
Fruquintinib versus fruquintinib combined with PD-1 inhibitors for metastatic colorectal cancer: Real-world data | Abstract # e15592 Publication Only Gastrointestinal Cancer–Colorectal and Anal | |
Phase II study of fruquintinib as second or further-line therapy for patients with advanced biliary tract cancer | Abstract # e16161 Publication Only Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary | |
A phase I/IIa study of cetuximab combined with fruquintinib in the previously treated RAS/BRAF wild-type metastatic colorectal cancer: Results of the CEFRU study | Abstract # e15558 Publication Only Gastrointestinal Cancer–Colorectal and Anal | |
SURUFATINIB | ||
A multicenter, single-arm phase 2 study of surufatinib plus toripalimab for patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer | Abstract # 6089 Poster Session Head and Neck Cancer | |
A multicenter, single-arm, phase 2 study of surufatinib plus toripalimab for patients with advanced endometrial cancer | Abstract # 5609 Poster Session Gynecologic Cancer | |
A phase 1b/2 study of surufatinib plus camrelizumab, nab-paclitaxel, and S-1 (NASCA) as first-line therapy for metastatic pancreatic adenocarcinoma (mPDAC) | Abstract # 4142 Poster Session Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary | |
A phase Ib/II study to evaluate surufatinib combined with camrelizumab and chemotherapy in the second-line treatment of advanced colorectal cancer: Phase Ib results | Abstract # 3555 Poster Session Gastrointestinal Cancer–Colorectal and Anal | |
Phase 1b/2 study of surufatinib in combination with docetaxel as second-line treatment of advanced driver-gene negative non-squamous non-small cell lung cancer (NSCLC) | Abstract # e21087 Publication Only Lung Cancer—Non-Small Cell Metastatic | |
Pathologic exploration of neuroendocrine differentiation in carcinomas | Abstract # e16238 Publication Only Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary | |
A phase II study of surufatinib in patients with osteosarcoma and soft tissue sarcoma who have failed in standard chemotherapy | Abstract # e23540 Publication Only Sarcoma | |
HMPL-453 | ||
A phase 2 study of HMPL-453, a selective FGFR tyrosine kinase inhibitor (TKI), in patients with previously treated advanced cholangiocarcinoma containing FGFR2 fusions | Abstract # e16118 Publication Only Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary |
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1 Sun Q, et al. (2014) Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy, Cancer Biol Ther. 2014 15:12, 1635-1645. Doi: 10.4161/15384047.2014.964087 |
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