cixutumumab (IMC A12) / Eli Lilly - LARVOL DELTA

Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer (clinicaltrials.gov) - P2 | N=94 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma

Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer (clinicaltrials.gov) - P2 | N=94 | Active, not recruiting | Sponsor: National Cancer Institute (NCI)

Metastases • Trial completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial. (PubMed, Oncologist) - P2 | "The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes relative to standard of care (ClinicalTrials.gov Identifier: NCT01142388)."

Journal • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Overall survival (OS) in metastatic uveal melanoma: A summary of recent prospective trials. (ASCO 2022) - "Tebentafusp (tebe), a TCR bispecific (gp100 x CD3), is the first therapy to demonstrate an OS benefit in a mUM randomized trial (IMCgp100-202) against pembrolizumab (pembro), ipilimumab (ipi) or dacarbazine... A literature review of prospective Ph2/3 clinical trials of systemic therapies in mUM published recently (2019-2021) identified 8 trials: in 1L mUM (n = 2) a randomized Ph3 of tebe (N = 252) vs investigator’s choice (IC; N = 126) of pembro, ipi or dacarbazine (IMCgp100-202) and a single arm Ph2 of nivolumab (nivo) + ipi (N = 52; Piulats, 2021) (Table); in 2L+ mUM (n = 1) a single arm Ph2 of tebe (N = 127; IMCgp100-102); and in mixed line mUM (n = 5) a randomized Ph2 of cabozantinib (N = 31) vs chemotherapy (N = 15; Luke, 2019), a single arm Ph2 of nivo + ipi (N = 35; Pelster, 2021), a single arm Ph2 of pembro + entinostat (N = 29; Ny, 2021), a single arm Ph2 of glembatumumab (N = 37; Hasanov, 2020), and a single arm Ph2 of IMC-A12 (IGF-1 receptor inhibitor; N = 18;..."

Clinical • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • IGF1

Survival outcomes and risk group validation from SWOG S0925, a randomized phase II study of androgen deprivation (AD) +/- cixutumumab, in new metastatic hormone-sensitive prostate cancer (mHSPC). (ASCO-GU 2020) - P2; "In new mHSPC, adding cixutumumab to AD did not improve survival measures. Baseline risk and disease volume carried prognostic value for this distinct trial population, though disease volume was a better predictor of survival. PSA treatment response was a strong intermediate endpoint for survival."

Clinical • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IGF1R

Comparison of Second-Line Treatments for Patients with Platinum-Resistant Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Systematic Review and Bayesian Network Meta-Analysis. (PubMed, Cancers (Basel)) - "These studies compared 20 different treatments, including the standard of care (SOC: docetaxel, methotrexate, or cetuximab), PD-1 inhibitors (nivolumab or pembrolizumab), durvalumab, tremelimumab, durvalumab + tremelimumab, palbociclib + SOC, tivantinib + SOC, sorafenib + SOC, EMD1201081 + SOC, vandetanib + SOC, PX-866 + SOC, 5-fluorouracil + SOC, cixutumumab + SOC, gefitinib + SOC, cabazitaxel, nolatrexed, duligotuzumab, zalutumumab, gefitinib, and afatinib. Afatinib presented a better PFS and ORR than the SOC. Compared with afatinib, the PD-1 inhibitor had a better OS but a worse PFS."

Journal • Retrospective data • Review • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Cixutumumab reveals a critical role for IGF-1 in adipose and hepatic tissue remodelling during the development of diet-induced obesity. (PubMed, Adipocyte) - "These data reveal an important role for IGF-1 R in the WAT and hepatic response to short-term nutrient excess. IGF-1 R inhibition during HFD leads to a lipodystrophic phenotype with a failure of WAT lipid storage and protection from HFD-induced hepatic insulin resistance."

Journal • Genetic Disorders • Lipodystrophy • Metabolic Disorders • Obesity • IGF1 • IR

S0727 Gemcitabine Hydrochloride and Erlotinib Hydrochloride With or Without Monoclonal Antibody Therapy in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery (clinicaltrials.gov) - P2 | N=134 | Completed | Sponsor: National Cancer Institute (NCI) | Phase classification: P1/2 ➔ P2

Phase classification • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • EGFR

Advances in targeted therapy for osteosarcoma based on molecular classification. (PubMed, Pharmacol Res) - "Therefore, we indicated the importance of molecular classification on the targeted therapy for osteosarcoma. And the stratification of patients based on the genetic characteristics of osteosarcoma will help to obtain a better therapeutic response to targeted therapies, bringing us closer to the era of personalized medicine."

Journal • Review • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

The Immunotherapy Landscape in Adrenocortical Cancer. (PubMed, Cancers (Basel)) - "Immunotherapies that have been evaluated in clinical trials for ACC include the immune checkpoint inhibitors pembrolizumab, nivolumab, and avelumab. Other immunotherapies that have been evaluated include the monoclonal antibodies figitumumab and cixutumumab directed against the ACC-expressed insulin-like growth factor 1 (IGF-1) receptor, the recombinant cytotoxin interleukin-13-pseudomonas exotoxin A, and autologous tumor lysate dendritic cell vaccine. These agents have shown modest clinical activity, although nonzero in the case of the immune checkpoint inhibitors. Clinical trials are ongoing to evaluate whether this clinical activity may be augmented through combinations with other immune-acting agents or targeted therapies."

Journal • Review • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Oncology • Solid Tumor • IGF1 • IL13

Randomized Phase II Trial of Capecitabine and Lapatinib with or without IMC-A12 (Cituxumumab) in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab and Chemotherapy: NCCTG N0733 (Alliance). (PubMed, Breast Cancer Res Treat) - P2 | "The addition of cituxumumab to lapatinib and capecitabine did not improve PFS or OS compared with lapatinib and capecitabine in patients with HER2-positive MBC."

Clinical • Journal • P2 data • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma (clinicaltrials.gov) - P2; N=30; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Suspended ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Brain Cancer • Embryonal Tumor • Ewing Sarcoma • Fibrosarcoma • Gliosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • IR • MRI • mTOR

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma (clinicaltrials.gov) - P2; N=30; Active, not recruiting; Sponsor: National Cancer Institute (NCI)

Clinical • Combination therapy • New P2 trial • Brain Cancer • Embryonal Tumor • Ewing Sarcoma • Fibrosarcoma • Gliosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • IR • MRI • mTOR

A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer (clinicaltrials.gov) - P2; N=93; Active, not recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Dec 2013 ➔ Sep 2014

Clinical • Combination therapy • Trial completion date • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • PGR

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma (clinicaltrials.gov) - P2; N=46; Completed; Sponsor: National Cancer Institute (NCI); Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Brain Cancer • Embryonal Tumor • Ewing Sarcoma • Fibrosarcoma • Gliosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • IR • MRI • mTOR

A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer (clinicaltrials.gov) - P2; N=93; Completed; Sponsor: Eli Lilly and Company; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • PGR

Cixutumumab and Temsirolimus in Treating Patients With Locally Advanced or Metastatic Cancer (clinicaltrials.gov) - P1; N=72; Completed; Sponsor: National Cancer Institute (NCI); Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Oncology • AKT1 • IRS1 • KDR • PTEN

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma (clinicaltrials.gov) - P2; N=30; Active, not recruiting; Sponsor: National Cancer Institute (NCI); N=92 ➔ 30

Clinical • Combination therapy • Enrollment change • Brain Cancer • Embryonal Tumor • Ewing Sarcoma • Fibrosarcoma • Gliosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • IR • MRI • mTOR

Cixutumumab and Temsirolimus in Treating Patients With Locally Advanced or Metastatic Cancer (clinicaltrials.gov) - P1; N=72; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Oncology • AKT1 • IRS1 • KDR • PTEN

An expanded genetic code facilitates antibody chemical conjugation involving the lambda light chain. (PubMed, Biochem Biophys Res Commun) - "Finally, o-Az-Z-Lys was incorporated into the Fab fragments of cixutumumab and trastuzumab to chemically combine them; the resulting bispecific Fab-dimers showed a strong antagonistic activity against a cancer cell line. The present results expand the utility of the chemical conjugation method to the whole spectrum of humanized antibodies, including the λ isotype."

Journal • Oncology

Development and preclinical evaluation of cixutumumab drug conjugates in a model of insulin growth factor receptor I (IGF-1R) positive cancer. (PubMed, Sci Rep) - "Cixutumumab-PEG-DM1-Low ADC was more effective. The study highlights the potential utility of cixutumumab-ADCs as theranostics against IGF-1R positive cancers."

Journal • Preclinical • Oncology • IGF1R

A phase II study of the insulin-like growth factor type I receptor inhibitor IMC-A12 in patients with metastatic uveal melanoma. (PubMed, Melanoma Res) - "IMC-A12 was very well tolerated, however, showed limited clinical activity in uveal melanoma as a single agent. Due to its low toxicity profile it could be studied in combination with other pathway-specific agents."

Clinical • Journal • P2 data • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

A Phase I Trial of IGF-1R Inhibitor Cixutumumab and mTOR Inhibitor Temsirolimus in Metastatic Castration-resistant Prostate Cancer. (PubMed, Clin Genitourin Cancer) - "Despite a strong scientific rationale for the combination, temsirolimus plus cixutumumab demonstrated limited antitumor activity and a greater than expected incidence of toxicity, including low-grade pneumonitis and hyperglycemia. Hence, the trial was stopped in favor of alternative androgen receptor/phosphatidylinositol 3-kinase-directed combinatorial therapies."

Journal • P1 data • Genito-urinary Cancer • Immunology • Mucositis • Oncology • Pneumonia • Prostate Cancer • Solid Tumor • Stomatitis • AR • CTCs • IGF1 • IGF1R • KLK3 • PTEN

Survival outcomes and risk group validation from SWOG S0925: a randomized phase II study of cixutumumab in new metastatic hormone-sensitive prostate cancer. (PubMed, Prostate Cancer Prostatic Dis) - "In new metastatic hormone-sensitive prostate cancer, addition of cixutumumab to androgen deprivation did not improve survival. Baseline risk and disease volume carried prognostic value for this distinct trial population, although disease volume added more prognostic information. PSA treatment response was a strong intermediate endpoint for survival."

Clinical • Journal • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IGF1R • KLK3

Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma (clinicaltrials.gov) - P2; N=179; Completed; Sponsor: National Cancer Institute (NCI); Active, not recruiting -> Completed ; Trial primary completion date: Dec 2016 ->Sep 2014

Trial completion • Trial primary completion date • Biosimilar • Oncology • Sarcoma