On May 25, 2023 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported preliminary Phase 1b data for ERAS-007 combinations in patients with GI malignancies from two poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Erasca, MAY 25, 2023, View Source [SID1234639355]). The posters will be available online at Erasca.com/science/presentations.

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"Early clinical data from HERKULES-3 continue to reinforce the potential to combine ERAS-007 with multiple agents and its potential as a backbone therapy to treat patients with GI malignancies. Importantly, these preliminary findings support a data-driven approach to refine the focus of our initial clinical development efforts on indications holding significant promise," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "Our initial evaluation of the ERAS-007 + EC combination in patients with BRAF-mutated metastatic CRC will focus on EC-naïve patients based on the preliminary activity observed in HERKULES-3. By evaluating efficacy and safety in a larger sample size of patients treated at the 100 mg BID-QW dose of ERAS-007 with EC, we believe we will be able to better assess whether the promising response rate and duration of treatment observed with the triplet can be maintained."

Poster Presentation Highlights

Abstract 3557 – Preliminary results from ERAS-007 plus encorafenib and cetuximab (EC) in patients (pts) with metastatic BRAF V600E-mutated colorectal cancer (CRC) in HERKULES-3 study: A phase 1b/2 study of agents targeting the mitogen-activated protein kinase (MAPK) pathway in pts with advanced gastrointestinal malignancies (GI cancers)

ERAS-007 in combination with encorafenib (BRAFTOVI) + cetuximab (ERBITUX) demonstrated promising preliminary clinical activity in EC-naïve patients with metastatic BRAF V600E-mutated CRC. EC is currently approved for the treatment of patients with metastatic BRAF V600E-mutated CRC, as detected by an FDA-approved test, after prior therapy; however, only approximately 20% of patients experience an objective response in the second and later line of treatment setting. Downstream ERK inhibition through ERAS-007 may prevent resistance to upstream BRAF/EGFR inhibition when combined with EC. As of the data cutoff date of March 23, 2023:

40% (2/5) response rate and 60% (3/5) disease control rate (complete response + partial response + stable disease) in EC-naïve response evaluable patients at the highest dose of ERAS-007 tested (100 mg BID-QW), with duration of exposure for both responders > 34 weeks as of the data cutoff date; across all dose levels in EC-naïve response evaluable patients, 29% (2/7) response rate and 57% (4/7) disease control rate
ERAS-007 + EC was generally well-tolerated with mostly low-grade adverse events at all combination doses tested
One dose-limiting toxicity (DLT) was reported for ERAS-007 100 mg BID-QW + EC (Grade 3 macular edema)
Pharmacokinetic (PK) exposures of ERAS-007, encorafenib, and cetuximab were comparable to monotherapy values, suggesting no clinically significant PK drug-drug interactions between the study drugs
Additional HERKULES-3 Phase 1b combination data in EC-naïve patients with BRAF-mutated CRC expected between H2 2023 and H1 2024

Abstract 3558 – Preliminary results from ERAS-007 plus palbociclib (palbo) in patients (pts) with KRAS/NRAS mutant (m) colorectal cancer (CRC) or KRASm pancreatic ductal adenocarcinoma (PDAC) in HERKULES-3 study: A phase 1b/2 study of agents targeting the mitogen-activated protein kinase (MAPK) pathway in pts with advanced gastrointestinal malignancies (GI cancers)

ERAS-007 in combination with palbociclib (IBRANCE) demonstrated a lack of clinical activity in patients with KRAS/NRAS mutant CRC and KRAS mutant PDAC. Palbociclib is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy or with fulvestrant in patients with disease progression following endocrine therapy. Based on these data, the combination of ERAS-007 and palbociclib will not be pursued further in this patient population.

Dr. Lim continued, "Our pioneering efforts exploring the potential of targeting adjacent pathways with terminal node inhibition of the RAS/MAPK pathway (ERAS-007) and cell cycle inhibition (palbociclib) did not demonstrate clinical activity in the initial evaluation. While we will not pursue further development of this combination in this patient population, it has contributed to our understanding and characterization of ERAS-007."

On May 25, 2023 Cellestia Biotech reported that the Investigator Initiated Phase II Trial at MD Anderson Cancer Center combining CB-103 and Venetoclax for the treatment of relapsed-refractory T cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL /LBL) is now open for recruitment (Press release, Cellestia Biotech, MAY 25, 2023, View Source [SID1234632333]).

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CB-103 is a small molecule transcriptional pan-NOTCH inhibitor with a novel mechanism of action. A Phase I clinical trial has shown promising safety and tolerability, proof of biological activity, and signs of efficacy. A new investigator- initiated trial (IIT) is starting at The University of Texas MD Anderson Cancer Center, in the departments of Pediatrics and Adult Leukemia, to combine the potential of NOTCH and BCL2 inhibition considering the biological synergies between the two pathways. CB-103, in combination with Venetoclax, will be tested for the treatment of relapsed-refractory T cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL in patients 12-40 years old). Added to the ongoing anti-leukemia treatment, CB-103 administration to a r/r T-ALL patient under a compassionate use program resulted in a complete response making the patient eligible for Hematopoietic Stem Cell Transplant. The IIT trial at MD Anderson is now open for patient recruitment.

On May 25, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast and gynecological cancers harboring ESR1 mutations, reported an abstract to be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting detailing the results of its ELAINE-2 clinical study with longer patient follow-up (Press release, Sermonix Pharmaceuticals, MAY 25, 2023, View Source [SID1234632148]). ASCO (Free ASCO Whitepaper) 2023 will be held June 2-6 at McCormick Place in Chicago.

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ELAINE-2 (NCT04432454), an open-label, Phase 2 Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) study of Sermonix’s lead investigational drug, lasofoxifene, in combination with Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib, evaluated 29 women with ER+/HER- metastatic breast cancer and an ESR1 mutation. The primary endpoint was safety/tolerability, with secondary endpoints including progression-free survival (PFS) and overall response rate (ORR). Earlier ELAINE-2 results were shared at ASCO (Free ASCO Whitepaper) 2022.

With patient follow-up through Jan. 31, 2023, the combination of lasofoxifene and abemaciclib continued to be well-tolerated, with clinically meaningful efficacy in women with ER+/HER- metastatic breast cancer and an ESR1 mutation. The previously reported PFS, a median of 13 months, and ORR of 50% were promising, with longer term follow-up to be provided at ASCO (Free ASCO Whitepaper) 2023. Encouraging Phase 2 monotherapy and combination results in ELAINE-1 and ELAINE-2 respectively led Sermonix in March to initiate ELAINE-3, a confirmatory Phase 3 randomized study. Enrolling 400 patients, ELAINE-3 will again assess the efficacy of the combination of lasofoxifene and abemaciclib compared to the combination of fulvestrant and abemaciclib.

"Sermonix is pleased that the combination of lasofoxifene and abemaciclib, which demonstrated compelling anti-tumor activity in ELAINE-2, continued to be well-tolerated when observed through a longer patient follow-up," said Dr. David Portman, founder and chief executive officer of Sermonix. "The results solidify our team’s excitement for ELAINE-3 enrollment and continue to point to a potential therapy with a favorable safety profile and the ability to address a critical unmet need for women confronted with metastatic breast cancer. We look forward to further discussing the results at ASCO (Free ASCO Whitepaper) 2023."

Details of Sermonix’s ASCO (Free ASCO Whitepaper) 2023 poster presentation are as follows:

Abstract Title: Lasofoxifene (LAS) plus abemaciclib (Abema) for treating ESR1-mutated ER+/HER2- metastatic breast cancer (mBC) after progression on prior therapies: ELAINE 2 study update.

Session Title: Breast Cancer—Metastatic
Session Date and Time: June 4, 2023, 8-11 a.m. CT
Sermonix will also convene meetings of its ELAINE-3 Steering Committee and ELAINE-3 Translational Committee while at ASCO (Free ASCO Whitepaper).

To learn more about Sermonix Pharmaceuticals and lasofoxifene, visit View Source

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with abemaciclib in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

On May 25, 2023 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported new and updated clinical data related to HUTCHMED’s novel investigational cancer therapies fruquintinib, surufatinib and HMPL-453 in 21 abstracts that will be presented at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6, 2023 in Chicago, IL and online (Press release, HUTCHMED, MAY 25, 2023, View Source [SID1234632142]).

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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 U.S., European and Japanese regulatory authorities for the treatment of previously treated metastatic colorectal cancer ("CRC"). FRESCO-2 results were first presented at the European Society for Medical Oncology Congress 2022. These new analyses add to the understanding of fruquintinib efficacy by specific lines of therapy as well as adverse events of special interest ("AESI"). In subgroup analyses by prior lines of therapies up to six or more and by prior treatment with approved agents, fruquintinib improved overall survival ("OS") and progression free survival ("PFS") for all subgroups and prior therapies, consistent with those of the intent-to-treat ("ITT") population. Furthermore, during the study AESIs led to low rates of dose reduction (13.6% for patients who received fruquintinib vs 0.9% for patients who received placebo) and dose discontinuation (8.3% for patients who received fruquintinib vs 6.1% for patients who received placebo).

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 China are consistent with the fruquintinib safety profile observed in existing clinical studies, with no new or significant safety signals identified.

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 November 30, 2022, median PFS was 15.9 months in 20 previously treated patients. Median PFS was not reached when results from this study were initially presented at the 2021 Chinese Society of Clinical Oncology Annual Meeting (data cut-off on August 31, 2021). No new safety signals were observed. A Phase II/III trial of fruquintinib in combination with sintilimab as second-line treatment for locally advanced or metastatic ccRCC was initiated in October 2022 (NCT05522231).

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 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (AACR 2023) showed that it has strong activity against FGFR-deregulated tumors, supporting investigation in patients with FGFR alterations (such as fusion and mutation) either as a single agent or in combination with PD-1 blockade.

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

Arvind Dasari, MD Anderson Cancer Center

Abstract # 3604
Poster Session
Gastrointestinal Cancer–Colorectal and Anal
Monday, June 5, 2023, 8 am CDT, Hall A

Analysis of fruquintinib adverse events of special interest from phase 3 of the FRESCO-2 study

Cathy Eng, Vanderbilt-Ingram Cancer Center

Abstract # 3601
Poster Session
Gastrointestinal Cancer–Colorectal and Anal
Monday, June 5, 2023, 8 am CDT, Hall A

A phase IV study to evaluate the safety of fruquintinib in Chinese real-world clinical practice

Jin Li, Tongji University Shanghai East Hospital

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

Dingwei Ye, Fudan University Shanghai Cancer Center

Abstract # e16514
Publication Only
Genitourinary Cancer—Kidney and Bladder

Abstract title

Presenter / Lead author

Presentation details

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

Wensi Zhao, Renmin Hospital of Wuhan University

Abstract # 3582
Poster Session
Gastrointestinal Cancer–Colorectal and Anal
Monday, June 5, 2023, 8 am CDT, Hall A

Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric adenocarcinoma (FRUTINEOGA): a multicenter, phase II study.

Liucheng Wu, Guangxi Medical University Cancer Hospital

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

Zhuqing Liu, Tongji University School of Medicine

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

Zhenyu Lin, Tongji Medical College

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

Zhiguo Luo, Fudan University Shanghai Cancer Center

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.

Jun Zhang, Reijin Hospital

Abstract # e15557
Publication Only
Gastrointestinal Cancer–Colorectal and Anal

Fruquintinib versus fruquintinib combined with PD-1 inhibitors for metastatic colorectal cancer: Real-world data

Lina He, Shanghai Jiao Tong University

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

Pengfei Zhang, West China Hospital

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

Yong Li, Traditional Chinese Medicine Hospital of Guangdong

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

Dongmei Ji, Fudan University Shanghai Cancer Center

Abstract # 6089
Poster Session
Head and Neck Cancer
Monday, June 5, 2023, 1:15 pm CDT, Hall A

A multicenter, single-arm, phase 2 study of surufatinib plus toripalimab for patients with advanced endometrial cancer

Guangwen Yuan, Cancer Hospital Chinese Academy of Medical Sciences

Abstract # 5609
Poster Session
Gynecologic Cancer
Monday, June 5, 2023, 1:15 pm CDT, Hall A

A phase 1b/2 study of surufatinib plus camrelizumab, nab-paclitaxel, and S-1 (NASCA) as first-line therapy for metastatic pancreatic adenocarcinoma (mPDAC)

Guanghai Dai, The Fifth Medical Center of the PLA General Hospital

Abstract # 4142
Poster Session
Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
Monday, June 5, 2023, 8:00 am CDT, Hall A

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

Sheng Li, Department of Oncology, Jiangsu Cancer Hospital

Abstract # 3555
Poster Session
Gastrointestinal Cancer–Colorectal and Anal
Monday, June 5, 2023, 8 am CDT, Hall A

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)

Wei Jiang, Guangxi Medical University Cancer Hospital

Abstract # e21087
Publication Only
Lung Cancer—Non-Small Cell Metastatic

Pathologic exploration of neuroendocrine differentiation in carcinomas

Yaru Wen, Cancer Hospital Chinese Academy of Medical Sciences

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

Xing Zhang, Sun Yat-sen University Cancer Center

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

Jianming Xu, Fifth Medical Center, Chinese PLA General Hospital

Abstract # e16118
Publication Only
Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepato­biliary

On May 25, 2023 Takeda (TSE:4502/NYSE:TAK) and HUTCHMED (China) Limited (Nasdaq/AIM:HCM, HKEX:13) (HUTCHMED) reported that the U.S. Food and Drug Administration (FDA) has granted priority review of the New Drug Application (NDA) for fruquintinib, a highly selective and potent inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2 and -3 for the treatment of adult patients with previously treated metastatic colorectal cancer (CRC) (Press release, Takeda, MAY 25, 2023, View Source [SID1234632126]). If approved, fruquintinib will be the first and only highly selective inhibitor of all three VEGF receptors approved in the U.S. for previously treated metastatic CRC.1,2 The Prescription Drug User Fee Act (PDUFA) goal date assigned by the FDA for this NDA is November 30, 2023.

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"We are confident that fruquintinib has the potential to transform the treatment landscape for those living with previously treated metastatic colorectal cancer, as demonstrated by its strong clinical profile," said Awny Farajallah, M.D., head of Global Medical Affairs Oncology at Takeda. "There are significant needs for patients with this disease in the U.S., and we believe fruquintinib has the potential to address these needs regardless of patients’ biomarker status. We look forward to continuing conversations with the FDA with the goal to make this therapy available to patients as soon as possible."

The NDA for fruquintinib includes results from the Phase 3 FRESCO-2 trial along with data from the Phase 3 FRESCO trial conducted in China. FRESCO-2 is a global Phase 3 multi-regional clinical trial (MRCT) conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus best supportive care (BSC) vs placebo plus BSC in patients with previously treated metastatic CRC. The FRESCO-2 trial met its primary and key secondary endpoints, showing a significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS), respectively. Fruquintinib has been generally well tolerated in patients to date.

"The clinical benefit of fruquintinib has been confirmed in multiple ways, from global clinical studies to commercialization in China. We are pleased to have Takeda as our partner furthering development and commercialization of fruquintinib outside of China," said Dr. Michael Shi, Head of R&D and Chief Medical Officer, HUTCHMED. "Today’s acceptance marks a significant advancement towards the goal of providing patients with previously treated metastatic colorectal cancer a much-needed therapeutic option, given the limited treatment options currently available to patients. This also supports our ongoing vision to design and develop differentiated molecules that help patients with high unmet needs globally."

Fruquintinib is currently approved in China under the brand name ELUNATE. Approval in China was based on the results of the FRESCO study, a Phase 3 pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, published in The Journal of the American Medical Association, JAMA, in June 2018 (NCT02314819).3 In March 2023, HUTCHMED and Takeda closed an exclusive licensing agreement to further the global development, commercialization and manufacture of fruquintinib outside of China.

About Fruquintinib

Fruquintinib is a highly selective and potent oral inhibitor of VEGFR -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity with the intention of minimizing off-target toxicities, improving tolerability and providing more consistent target coverage. Fruquintinib has been generally well tolerated in patients to date and is being investigated in combinations with other anti-cancer therapies.

About FRESCO-2

The FRESCO-2 study is a multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus BSC vs placebo plus BSC in patients with previously treated metastatic CRC. As previously disclosed, the 691-patient study met its primary endpoint of OS in patients with metastatic CRC who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to OS, a statistically significant improvement in PFS, a key secondary endpoint, was observed. Fruquintinib has been generally well tolerated in patients to date. Summary results were initially presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September 2022.4 Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04322539.

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with 935,000 deaths in 2020.5 In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2023.6 In Europe, CRC was the second most common cancer in 2020 with approximately 520,000 new cases and 245,000 deaths. In Japan, CRC was the most common cancer with an estimated 148,000 new cases and 60,000 deaths in 2020.5 Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.