ganitumab (AMG 479) / Takeda, ImmunityBio - LARVOL DELTA

Haematological toxicities with targeted drugs in tumors: A systematic review and network meta-analysis of randomized controlled trials (ASH 2025) - "1 patient treated with sorafenib plus chemotherapy was reported to have died as a result of pancytopenia and 1 patient treated with chemotherapy (gemcitabine plus cisplatin) died due to anemia. Our study confirmed that chemotherapy with or without a placebo, one targeted drug with chemotherapy was associated with more severe hematologic toxicities compared with the use of one targeted drug, tepotinib plus gefitinib, tivantinib plus erlotinib. In the targeted drug monotherapy category, for the primary outcome, we found that alectinib and gefitinib had a higher risk of all-grade (grade 1-5) and severe-grade (grade 3-5) anemia, respectively...Ganitumab plus chemotherapy had the highest risk of grade 1-5 anemia and thrombocytopenia. Afatinib plus chemotherapy had the highest risk of grade 3-5 anemia and thrombocytopenia. Ramucirumab plus chemotherapy had the highest risk of grade 1-5 and 3-5 neutropenia. Veliparib plus chemotherapy had the highest risk of grade 1-5 and 3-5..."

Retrospective data • Review • Febrile Neutropenia • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia

Downregulation of Insulin-Like Growth Factor I (IGF-1) Signaling Induces Cell Senescence in Vascular Smooth Muscle Cells: Implications for Atherosclerotic Plaque Progression (AHA 2025) - "Cell senescence is an irreversible cell proliferation arrest associated with the progression of atherosclerosis, however specific mechanisms linking senescence with atherogenesis remain to be identified.Hypothesis: We hypothesized that IGF1 receptor (IGF1R) downregulation would induce SMC senescence in vitro and that activation of IGF1R signaling would suppress SMC senescence in the atherosclerotic plaque. Bleomycin (10ug/ml, 5d)-treated aortic SMC were used as in vitro senescence model...SMC treatment with 3uM picropodophyllin (IGF1R inhibitor) or with 100nM ganitumab (IGF1R antibody) decreased IGF-1-induced signaling, arrested SMC proliferation and upregulated senescence markers (βGal activity and γ-H2AX expression) showing that specific inhibition of IGF-1 signaling induces cell senescence... IGF1R downregulation induced SMC senescence in vitro and activation of IGF1R signaling downregulated senescence markers, and decreased levels of SMC-like senescent cells in the..."

Atherosclerosis • APOE • CDKN1A • H2AX • IGF1 • IGF1R

AEWS1221: Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma (clinicaltrials.gov) - P3 | N=312 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Embryonal Tumor • Ewing Sarcoma • Lung Cancer • Oncology • Sarcoma • Solid Tumor

Immune and Growth Factor Signaling Pathways Are Associated with Pathologic Complete Response to an Anti-Type I Insulin-like Growth Factor Receptor Regimen in Patients with Breast Cancer. (PubMed, Clin Cancer Res) - "Pretreatment specimens from patients treated on the I-SPY2 neoadjuvant breast cancer trial were studied to identify prespecified biomarkers associated with response to the regimen of paclitaxel, the anti-type I insulin-like growth factor receptor (IGF-1R) antibody ganitumab, and metformin (PGM) followed by doxorubicin and cyclophosphamide (AC) compared with control therapy (paclitaxel followed by AC). Immune activation markers were also associated with response in HR+ and HR- subgroups. Thus, IGF-1R may directly regulate tumor biology and associate with immune response to therapy."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • STAT1

Comprehensive Genomic and Proteomic Profiling of Adrenocortical Carcinoma in Chinese Patients Identifies an IDH1-Mutant Subtype with Therapeutic Implications (UAA 2025) - "IDH1 mutations are highly prevalent in Chinese ACC patients and are associated with glycolysis and hypoxia activation, leading to IGF-1R signaling upregulation. Our preclinical findings support a combination of ivosidenib and ganitumab as a promising treatment for IDH1-mutated ACC."

Clinical • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CTNNB1 • IDH1 • IDH2 • TP53

Systematic screening of metabolic pathways to identify two breast cancer subtypes with divergent immune characteristics. (PubMed, Sci Rep) - "Drug sensitivity analysis revealed that BCMS-II was highly sensitive to Ganitumab, Carboplatin + ABT-888, and Pembrolizumab. Our findings highlight the heterogeneity of BRCA in terms of metabolic features, immune characteristics, clinical prognosis, and drug sensitivity. The novel classification system provides valuable insights for clinical diagnosis and treatment, serving as a foundation for precision diagnosis and personalized therapies in BRCA."

Journal • Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • BRCA

Implantable Microdevice for the Delivery of Drugs and Their Effect on Tumors in Patients With Metastatic or Recurrent Sarcoma (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Phase classification: P1 ➔ P=N/A

Phase classification • Oncology • Sarcoma • Solid Tumor

AEWS1221: Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma (clinicaltrials.gov) - P3 | N=312 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2024 ➔ Sep 2025

Metastases • Trial completion date • Embryonal Tumor • Ewing Sarcoma • Lung Cancer • Oncology • Sarcoma • Solid Tumor • EGFR

Insulin-like growth factor binding protein 7 induces cell senescence in vitro and is associated with cell senescence in the advanced atheroma. (AHA 2024) - "BP7/IGF1R binding was quantified by proximity ligation assay (PLA). Bleomycin arrested SMC proliferation at 16h, upregulated senescence markers (beta-galactosidase and γH2A.X histone), and elevated BP7 levels in CM (3-fold increase, P<0.05) showing that SC secrete and upregulate BP7...BP7 overexpression (with pCMV-IGFBP7 vector) or inhibition of IGF1R (using Ganitumab, IGF1R antibody) suppressed cell proliferation, and upregulated senescence markers... SC upregulate BP7 and BP7 inhibits IGF1 signaling. Upregulated BP7 induces senescence in vitro and it was associated with SC in the advanced coronary plaque. Our results suggest a novel role of BP7 in senescence and atherogenesis and identify BP7 as a potential target for anti-atherogenic therapy."

Metastases • Preclinical • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Heart Failure • IGF1 • IGFBP7

QUILT-2.019: A Study of AMG 655 or AMG 479 in Combination With Gemcitabine for Treatment of Metastatic Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=138 | Completed | Sponsor: NantCell, Inc. | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Metastases • Phase classification • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Targeting IGF-IR improves neoadjuvant chemotherapy efficacy in breast cancers with low IGFBP7 expression. (PubMed, NPJ Precis Oncol) - "We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab, an anti-IGF-1R monoclonal antibody, to neoadjuvant chemotherapy, substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone...Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1R targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed."

Journal • Breast Cancer • Oncology • Solid Tumor • IGFBP7

QUILT-2.017: Phase 1b/2 Study of AMG 479 in Combination With Paclitaxel and Carboplatin for 1st Line Treatment of Advanced Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=15 | Terminated | Sponsor: NantCell, Inc. | Phase classification: P1b/2 ➔ P1/2 | N=49 ➔ 15

Combination therapy • Enrollment change • Metastases • Phase classification • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

QUILT-2.013: First-Line Treatment for Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=213 | Terminated | Sponsor: NantCell, Inc. | Phase classification: P1b/2 ➔ P1/2 | Completed ➔ Terminated; Subjects discontinued study

Combination therapy • Phase classification • Trial termination • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

QUILT-3.026: AMG 655 in Combination With AMG 479 in Advanced, Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=89 | Terminated | Sponsor: NantCell, Inc. | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Metastases • Phase classification • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Solid Tumor

Panitumumab Combination Study With Rilotumumab or Ganitumab in Wild-type Kirsten Rat Sarcoma Virus Oncogene Homolog (KRAS) Metastatic Colorectal Cancer (mCRC) (clinicaltrials.gov) - P1/2 | N=177 | Completed | Sponsor: NantBioScience, Inc. | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Metastases • Phase classification • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Sarcoma • Solid Tumor • KRAS

Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma. (PubMed, Cancers (Basel)) - "However, the growth of both primary and metastatic tumors was observed in animals receiving the combination of trametinib and ganitumab. Therefore, more preclinical work is necessary before testing this combination in patients with relapsed or refractory RAS-mutated neuroblastoma."

Journal • Preclinical • CNS Tumor • Neuroblastoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor

Palbociclib + Ganitumab In Ewing Sarcoma (clinicaltrials.gov) - P2 | N=10 | Terminated | Sponsor: Dana-Farber Cancer Institute | Completed ➔ Terminated; The study closed early due to discontinuation of ganitumab supply.

Trial termination • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • CDK4 • EWSR1 • FLI1 • FUS • IGF1

GAMMA: QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P3 | N=800 | Completed | Sponsor: NantCell, Inc. | Terminated ➔ Completed

Trial completion • Endocrine Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma (Multidisciplinary Digital Publishing Institute) - "In this study, trametinib and ganitumab synergistically suppressed neuroblastoma cell proliferation and induced apoptosis in cell culture. We also observed a delay in tumor initiation and prolongation of survival in heterotopic and orthotopic xenograft models treated with trametinib and ganitumab. However, the growth of both primary and metastatic tumors was observed in animals receiving the combination of trametinib and ganitumab."

Preclinical • Neuroblastoma

Association of elevated ctDNA burden following one cycle of chemotherapy with inferior outcomes for patients with metastatic Ewing sarcoma: A report from the Children's Oncology Group (COG). (ASCO 2024) - " AEWS1221 was a randomized phase 3 trial evaluating ganitumab plus interval compressed chemotherapy (vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide given every 2 weeks) for patients with newly diagnosed metastatic EWS. ctDNA burden ≥0.5% following one cycle of chemotherapy identifies patients highly likely to relapse, albeit in a small cohort with available data at that timepoint. Conversely, ctDNA at a cutpoint of ≥0.5% after two cycles of chemotherapy was not prognostic, suggesting either more sensitive assays are needed or the prognostic value of ctDNA burden is diminished following additional therapy. These findings will enable novel trials of risk-adapted therapy focused on baseline and early ctDNA burden."

Circulating tumor DNA • Clinical • Metastases • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • DUX4 • EWSR1

Low IGFBP7 expression identifies a subset of breast cancers with favorable prognosis and sensitivity to IGF-1 receptor targeting with ganitumab: Data from I-SPY2 and SCAN-B (AACR 2024) - P, P2 | "Low IGFBP7 gene expression identifies a subset of breast cancer patients for whom the addition of ganitumab and metformin to chemotherapy results in a significantly improved pCR rate compared to neoadjuvant chemotherapy alone. Furthermore, we add to prior evidence that high IGFBP7 expression is predictive of poor outcome."

Late-breaking abstract • Breast Cancer • Oncology • Solid Tumor • IGF1 • IGFBP7

Implantable Microdevice for the Delivery of Drugs and Their Effect on Tumors in Patients With Metastatic or Recurrent Sarcoma (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor

[PREPRINT] Low IGFBP7 expression identifies a subset of breast cancers with favorable prognosis and sensitivity to IGF-1 receptor targeting with ganitumab: Data from I-SPY2 and SCAN-B (medRxiv) - "Higher IGFBP7 expression conferred lower odds of achieving pCR in the ganitumab/metformin plus chemotherapy arm, ORadj 0.38 (95% CI 0.17-0.80) but not in the chemotherapy-alone arm, adjusted OR 1.23 (95% CI 0.63-2.45; Pinteraction=0.016). In the ganitumab/metformin plus chemotherapy arm, 46.9% of patients with tumors in the lowest quartile of IGFBP7 expression achieved pCR compared to compared to only 5.6% in the highest quartile. In SCAN-B, higher IGFBP7 expression was associated with distant metastasis risk HRadj 1.41 (95% CI 1.16-1.73)."

Observational data • P2 data • Preprint • Breast Cancer • Oncology • Solid Tumor

Results from the Children's Oncology Group phase III trial of a monoclonal antibody against the insulin-like growth factor-1 receptor in patients with newly diagnosed metastatic Ewing sarcoma. (PubMed, Transl Pediatr) - No abstract available

Journal • Metastases • P3 data • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor

Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma (clinicaltrials.gov) - P3 | N=312 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2023 ➔ Sep 2024

Metastases • Trial completion date • Embryonal Tumor • Ewing Sarcoma • Lung Cancer • Oncology • Sarcoma • Solid Tumor