ficlatuzumab (AV-299) / Biodesix, LG Chem, Xoma - LARVOL DELTA

Phase 1b safety run-in study followed by Phase 2 study of ficlatuzumab, azacitidine and venetoclax in untreated Acute Myeloid Leukemia patients aged ≥ 60 years old (ASH 2025) - P1, P1/2 | "In a primary induction refractory AML population, ficlatuzumab incombination with high dose cytarabine had a complete response of 53% with minimal toxicities(NCT02109627). Potential additional studies will explore biomarkers of responseand resistance to ficlatuzumab using multiomic platforms. The study will begin enrollment in fall 2025 atall Beat AML research sites."

Clinical • P1 data • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • HGF

Blood Cancer United will present findings from four sub-studies from its Beat AML Master Clinical Trial and Pediatric Acute Leukemia Master Clinical Trial (PedAL). (PRNewswire) - "A trial in progress poster presentation introduces a Beat AML sub-study assessing the efficacy of the combination of ficlatuzumab, a first-in-class anti-hepatocyte growth factor antibody, with azacytidine and venetoclax. The abstract from PedAL—the first integrated, global, pediatric acute leukemia master clinical trial—identifies opportunities to optimize treatments for children with AML."

Clinical data • Trial status • Acute Myelogenous Leukemia

Hepatocyte Growth Factor Is Overexpressed in AML and Remodels the Mesenchymal Stromal Cell Niche (ASH 2024) - "Ficlatuzumab is an anti-HGF (hepatocyte growth factor) antibody that has demonstrated effectiveness in relapsed/refractory AML with an overall response rate of 53% observed in a phase 1b clinical trial (Wang et al, 2021)...al 2014); MSCs were the dominant producer of wnt3, 4, 6 and 9. Together, these in vivo data point to a novel set of complex interactions between hematopoietic cells and MSCs which may have relevance for therapeutic resistance in AML."

Stroma • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD44 • HGF • HGFAC • MET • RUNX1 • WNT3

FIERCE-HN: A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of ficlatuzumab (HGF/cMET MAb) in combination with cetuximab in participants with recurrent or metastatic (R/M) HPV negative head and neck squamous cell carcinoma (HNSCC). (ASCO 2025) - P3 | "2023. 41:3851."

Clinical • Combination therapy • Metastases • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MET

Next-gen Korean cancer fighters to showcase innovation at ASCO 2025 (Korea Biomedical Review) - "Among the companies presenting clinical results is LG Chem, which will showcase phase 3 data for Fotivda (ingredient: tivozanib), its targeted therapy for metastatic renal cell carcinoma, developed by its U.S. subsidiary AVEO...Results demonstrated favorable progression-free survival in the monotherapy arm, particularly among patients who had previously received Yervoy and Opdivo. AVEO will also present phase 3 data on ficlatuzumab, an HGF-targeting antibody in head and neck cancer, and phase 1b data for AV-380, an anti-GDF15 antibody in development for cancer cachexia."

Clinical data • Cachexia • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Poster Title: "FIERCE-HN: A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of ficlatuzumab (HGF/cMET Mab) in combination with cetuximab in participants with recurrent or metastatic (R/M) HPV negative head and neck squamous cell carcinoma (HNSCC)."– (Abstract: TPS6115; Poster: 520a) (PRNewswire) - "AVEO presented a trial in progress poster for the Phase 3 FIERCE-HN trial, which is evaluating the combination of ficlatuzumab and cetuximab in patients with recurrent or metastatic (R/M) HPV-negative head and neck squamous cell carcinoma (HNSCC). The purpose of this study is to evaluate the efficacy and safety of ficlatuzumab (10 or 20 mg/kg) in combination with cetuximab (500 mg/kg) against placebo plus cetuximab in participants with HPV-negative R/M HNSCC. The study is evaluating whether ficlatuzumab combined with cetuximab is superior to cetuximab alone in terms of overall survival....FIERCE-HN opened for enrollment in December 2023 and currently expects to complete enrollment by May 2026."

Trial status • Squamous Cell Carcinoma of Head and Neck

AVEO Oncology, an LG Chem company, Announces Three Poster Presentations at ASCO 2025 Annual Meeting (PRNewswire) - "AVEO Oncology, an LG Chem company...announced today that three abstracts were accepted for presentation at the upcoming American Society of Clinical Oncology (ASCO) 2025 annual meeting this May 30-June 3, 2025, in Chicago, IL."

P1 data • P3 data • Cachexia • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

FIERCE-HN: A Multicenter, Randomized, Placebo-Controlled, Phase 3 Study of Ficlatuzumab + Cetuximab in Pts W/ Recurrent or Metastatic (R/M) HPV-Negative Head and Neck Squamous Cell Carcinoma (HNSCC) (ASTRO 2024) - "Purpose/Objective(s): For patients with R/M HNSCC, current treatments are palliative with anti-PD-1 checkpoint inhibitor +/- platinum and 5-fluorouracil chemotherapy for first-line followed by taxanes, methotrexate, and cetuximab as later-line options. TBD"

Clinical • Metastases • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MET

FIERCE-HN: A multicenter, randomized, placebo-controlled, phase 3 study of ficlatuzumab + cetuximab in pts w/ recurrent or metastatic (R/M) HPV-negative head and neck squamous cell carcinoma (HNSCC) (MHNCS 2024) - "Purpose/Objective(s): For patients with R/M HNSCC, current treatments are palliative with anti-PD-1 checkpoint inhibitor +/- platinum and 5-fluorouracil chemotherapy for first-line followed by taxanes, methotrexate, and cetuximab as later-line options. TBD"

Clinical • Metastases • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MET

AVEO Oncology Enrolls First Patient in Pivotal FIERCE-HN Clinical Trial to Evaluate Ficlatuzumab in Combination with ERBITUX (cetuximab) in Patients with HPV-negative Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (GlobeNewswire) - "AVEO Oncology ('AVEO'), an LG Chem company, today announced enrollment of the first patient in the FIERCE-HN trial, a global, multicenter, randomized, double-blind, placebo-controlled, phase 3 clinical trial evaluating ficlatuzumab in combination with ERBITUX^® (cetuximab), an anti-EGFR antibody, in patients with human papillomavirus (HPV)-negative recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC)."

Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

FIERCE-HN: A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P3 | N=410 | Recruiting | Sponsor: AVEO Pharmaceuticals, Inc.

Combination therapy • Metastases • Trial completion date • Trial initiation date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MET

FIERCE-HN: A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P3 | N=410 | Recruiting | Sponsor: AVEO Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MET

FIERCE-HN: a multicenter, randomized, placebo-controlled, phase 3 study of ficlatuzumab + cetuximab in pts w/recurrent or metastatic (R/M) HPV-negative head and neck squamous cell carcinoma (HNSCC) (SITC 2023) - "Trial Registration NCT number TBD Background For patients with R/M HNSCC, current treatments are palliative with anti-PD-1 checkpoint inhibitor +/- platinum and 5-fluorouracil chemotherapy for first-line followed by taxanes, methotrexate, and cetuximab as later-line options. Analysis will use a 1-sided log-rank test at a significance level= 0. 025 and the uniformly most powerful conditionally unbiased criterion to control the Type 1 error."

Clinical • Metastases • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MET

FIERCE-HN: A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P3 | N=410 | Not yet recruiting | Sponsor: AVEO Pharmaceuticals, Inc.

Combination therapy • Metastases • New P3 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MET

Will LG Chem's cancer drug enter phase 3 trial in US? (Korea Biomedical Review) - P2 | N=78 | NCT03422536 | "AVEO Pharmaceuticals, a subsidiary of LG Chem, has completed the U.S. phase 2 clinical trial of ficlatuzumab, a head and neck cancer candidate, and published the results in an international journal....Results showed that researchers discontinued the single-dose regimen of ficlatuzumab due to lack of efficacy. Combined with cetuximab, the mPFS was 3.7 months (90 percent CI, 2.3 months; P=0.04), meeting the primary endpoint. The ORR as the secondary endpoint was 19 percent (six of 32 patients), with two CRs (complete remissions) and four PRs (partial remissions) confirmed."

P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

P30CA023074: Ficlatuzumab w/wo Cetuximab in Patients w/Cetuximab-Resistant, Recurrent or Metastatic Head/Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=78 | Completed | Sponsor: University of Arizona | N=60 ➔ 78

Enrollment change • Breast Cancer • Head and Neck Cancer • Lip Cancer • Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma • Oncology • Oral Cancer • Oropharyngeal Cancer • Otorhinolaryngology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • CD27

Combination exhibits ‘impressive’ activity in HPV-negative head and neck cancer (Healio) - "'Preclinical data and biomarker studies suggested you can see upregulation of cMet after EGFR targeting,' Burtness said. 'It's not necessarily mutated or amplified in most cases, but its expression is increased, so the possibility you could target this alone or in combination with EGFR inhibition was exciting.'...Bauman called the response rate in the HPV-negative group 'gratifying,' noting in a press release that the expected response rate in this heavily pretreated group would be about 5%."

Media quote

Novel immunotherapy approaches in metastatic head and neck cancer (YouTube) - "Nabil Saba, MD, FACP...gives an overview of developments in utilizing immunotherapy for patients with metastatic head and neck cancer. The combination of PD-1 and VEGF inhibitors such as pembrolizumab and cabozantinib is a promising strategy, and findings from the LEAP-010 trial (NCT04199104) of pembrolizumab with lenvatinib further demonstrated the efficacy of this combination. Cetuximab with ficlatuzumab has additionally been assessed in a Phase II trial (NCT03422536) in patients with HPV-negative head and neck cancer. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Annual Congress in Chicago, IL."

Interview • Video

Phase Ib and Expansion Study of Gemcitabine, Nab-Paclitaxel, and Ficlatuzumab in Patients With Metastatic Pancreatic Cancer. (PubMed, Oncologist) - "In this phase Ib trial, ficlatuzumab, gemcitabine, and albumin-bound paclitaxel were associated with durable treatment responses and increased rates of hypoalbuminemia and edema."

Journal • Metastases • P1 data • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MET

Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer. (PubMed, J Clin Oncol) - "The ficlatuzumab-cetuximab arm met significance criteria for PFS and warrants phase III development. HPV-negative HNSCC merits consideration as a selection criterion."

IO biomarker • Journal • Metastases • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

New Drug Combination Holds Hope for Some Cancer Patients (The George Washington University) - "'Our study was conducted in patients with heavily resistant head and neck cancer, whose cancer had continued to grow in the face of all standard treatments including cetuximab,' said Julie E. Bauman, the study's lead author...'In this pan-refractory population, the combination of drugs doubled the expected time until cancer progression.'"

Media quote

Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer (J Clin Oncol) - P2 | N=60 | NCT03422536 | "This multicenter, randomized, noncomparative phase II study evaluated ficlatuzumab, an antihepatocyte growth factor mAb, with or without cetuximab in recurrent/metastatic HNSCC....From 2018 to 2020, 60 patients were randomly assigned and 58 were treated....The monotherapy arm closed early for futility. The combination arm met prespecified significance criteria with a median PFS of 3.7 months (lower bound 90% CI, 2.3 months; P = .04); the ORR was 6 of 32 (19%), including two complete and four partial responses. Exploratory analyses were limited to the combination arm: the median PFS was 2.3 versus 4.1 months (P = .03) and the ORR was 0 of 16 (0%) versus 6 of 16 (38%; P = .02) in the HPV-positive versus HPV-negative subgroups, respectively."

P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Computational Drug Discovery in Ankylosing Spondylitis-induced Osteoporosis Based on Data Mining and bioinformatics analysis. (PubMed, World Neurosurg) - "In conclusion, CARLUMAB, BERMEKIMAB, RILONACEPT, RILOTUMUMAB and FICLATUZUMAB were first identified as the potential drugs for the treatment of AS-OP, proving the value of text mining and pathway analysis in drug discovery."

Journal • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Orthopedics • Osteoporosis • Rheumatology • Seronegative Spondyloarthropathies

LG Chem aims to release four new drugs by 2030 after Aveo acquisition deal closure (Korea Biomedical Review) - "LG Chem said on Thursday that it invested 707.2 billion won ($571 million) to complete the acquisition of Aveo Pharmaceuticals, a U.S. oncology-specializing biopharma firm, through LG Chem Life Science Innovation Center, and will finalize the last details of the merger on Friday this week....Through the acquisition of Aveo, LG Chem plans to transfer the new anticancer drug pipeline developed by LG Life Sciences to Aveo in the mid-to-long term to accelerate the commercialization of new anticancer drugs in the U.S....To secure global competitiveness through global new drugs, the company will invest 2 trillion won in R&D from this year by 2027 to release at least four new drugs in the field of anticancer and metabolic disease in the U.S. and other global markets by 2030....This includes late-stage drugs from Aveo’s anticancer pipeline such as ficlatuzumab together with LG Chem’s LC350189 (ingredient: tigulixostat) for gout."

M&A • Gout • Oncology

Phase I study of the anti-HGF monoclonal antibody (mAb), ficlatuzumab, and cetuximab in cetuximab-resistant, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). (ASCO 2017) - P1b; "The RP2D is cetuximab 500 mg/m2 and ficlatuzumab 20 mg/kg every 2 weeks. This well-tolerated combination demonstrated promising activity in pts with poor prognosis, cetuximab-resistant R/M HNSCC. Phase II testing is justified."

P1 data • Biosimilar • Head and Neck Cancer • Immunology • Lung Cancer • Venous Thromboembolism