labetuzumab govitecan (IMMU-130) / Gilead - LARVOL DELTA

Understanding the Chemical Characteristics of Payloads and the Expression of Tumor-Associated Antigens of ADCs in Clinical Development. (PubMed, ACS Omega) - "Regarding the conjugation type, only trastuzumab deruxtecan, labetuzumab govitecan, sacituzumab govitecan, BYON3521, and SYD1875 used homogeneous conjugation. An interesting observation was that for some ADCs, TAA expression was higher in normal tissue than in the tumor. In summary, our analysis highlights that only a limited number of ADCs incorporate payloads with favorable physicochemical properties and that several ADCs currently under development target TAAs with higher expression in normal tissues than in the corresponding tumors."

Journal • Review • Oncology • EGFR • FOLR1 • HER-2

Antibody-Drug Conjugates in Colorectal Cancer: A Scoping Review of Current Evidence and Emerging Clinical Trends (ISPOR-EU 2025) - "ADCs such as trastuzumab deruxtecan (HER2), sacituzumab govitecan (TROP-2), and labetuzumab govitecan (CEACAM5) showed ORRs of 7%-45% and PFS of 2-6 months. Early-phase studies suggest modest clinical benefit of ADCs in heavily pretreated CRC, particularly in HER2-, TROP-2-, and CEACAM5-positive cases. The data underscore the need for better biomarker-driven selection, rational combinations, and earlier-line evaluation to define their role in CRC management."

Clinical • Review • Colorectal Cancer • Fatigue • Neutropenia • Oncology • Solid Tumor • CEACAM5 • HER-2 • MET

Preclinical evaluation of a highly efficacious next-generation CEACAM5 (CEA) ISAC comprising a novel CEA-specific mAb and TLR7/8 agonist (SITC 2025) - "The new CEA ISAC is active in human, non-human primate and mouse systems and has several advantages over reference CEA antibodies such as tusamitamab and labetuzumab.Results Our novel CEA mAb, P601 binds with high affinity and selectivity to human and cynomolgus CEA+ cells. The CEA ISAC compares favorably to other CEA-targeted modalities and inhibited tumor growth at lower doses than cytotoxic ADCs. Finally, in a non-GLP NHP toxicology study the next-generation CEA ISAC was well-tolerated with no significant drug-related adverse events observed up to 15 mg/kg, the highest dose tested.Conclusions These pre-clinical data demonstrate induction of a robust innate and adaptive immune response by our next-generation CEA-targeted ISAC and the potential to treat CEACAM5+ human cancers."

Preclinical • Oncology • CEACAM5 • TLR7

Multimodal carcinoembryonic antigen-targeted fluorescence and radio-guided cytoreductive surgery for peritoneal metastases of colorectal origin: single-arm confirmatory trial. (PubMed, BJS Open) - "This study confirmed the safety and feasibility of multimodal image-guided surgery in patients with peritoneal metastases."

Journal • Oncology • Peritoneal Cancer • CEACAM5

CEACAM5-Targeted Immuno-PET in Androgen Receptor-Negative Prostate Cancer. (PubMed, J Nucl Med) - "[89Zr]Zr-DFO-labetuzumab imaging was able to clearly delineate both neuroendocrine H660 xenografts and AR- DU145 in vivo but could not detect the AR-positive xenograft LNCaP. Immuno-PET imaging with [89Zr]Zr-DFO-labetuzumab is a promising diagnostic tool for AR- prostate cancer."

Journal • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • AR • CEACAM5

Study of Labetuzumab Govitecan in Participants With Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=92 | Terminated | Sponsor: Gilead Sciences | Withdrawn ➔ Terminated

Metastases • Trial termination • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Investigating the efficacy of an Adjuvant immunotherapy for preventing colorectal liver metastases - The CCaLM trial (ANZCTR) - P2 | N=66 | Not yet recruiting | Sponsor: St George Hospital

IO biomarker • New P2 trial • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Superior SN-38 pharmacodynamic and tumor-accretion profiles of labetuzumab govitecan (IMMU-130) versus irinotecan in experimental human colonic cancer models (AACR 2017) - P1/2; "IMMU-130 delivers >300-fold more SN-38 to CEA-producing tumors compared to irinotecan, while also reducing levels of potentially harmful SN-38 and SN-38G in normal tissues. These observations are consistent with preclinical data showing improved efficacy and safety."

Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin. (PubMed, Nat Commun) - P1/2 | "In this study (ClinicalTrials.gov NCT03699332) we describe the results of a phase I clinical trial evaluating [In]In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-carcinoembryonic antigen (anti-CEA) antibody conjugate that enables both preoperative imaging and intraoperative radioguidance and fluorescence imaging...Alteration of clinical strategy based on multimodal imaging occurred in three patients. Thus, multimodal image-guided surgery after administration of this dual-labeled tracer is a promising approach that may aid in decision making before and during cytoreductive surgical procedures."

Journal • Oncology • CEACAM5

BDC-2034: Discovery of a CEA-targeting immune-stimulating antibody conjugate (ISAC) for solid tumors (SITC 2021) - "Results Antibody CEA1 binds to the CEA protein with high affinity (EC50 = 0.25 nM), binds selectively to CEA-positive tumor cell lines, and mediates ADCP more efficiently than a reference anti-CEA antibody, labetuzumab (figure 1). Conclusions These pre-clinical data demonstrate the potential of BDC-2034 to treat CEA-expressing human cancers. Most importantly, the antigen-dependent induction of immune-stimulating cytokines promises a robust immune response that combines the activation of innate and adaptive arms."

Oncology • Solid Tumor • CEACAM5 • CXCL10 • TLR8 • TNFA

[VIRTUAL] Multimodal fluorescence-guided surgery of colorectal peritoneal metastases, a phase I/II clinical trial. (ASCO 2020) - P1/2 | " In this phase I/II single arm protein dose escalation study patients with peritoneal metastases of colorectal origin who are scheduled for cytoreductive surgery and HIPEC will receive an intravenous injection of the CEA-targeting tracer 111In-DOTA-labetuzumab-IRDye800CW...The secondary objectives are to assess whether additional malignant lesions can be visualized by fluorescence imaging after cytoreductive surgery, to assess the intensity of fluorescence in malignant and non-malignant tissue, to assess the correlation between localization of the dual-labeled antibody and CEA expression in tumor and healthy tissue and to determine blood concentrations of the dual labelled antibody at several time points in patients. Research Funding: Dutch Cancer Foundation"

Clinical • P1/2 data • Colorectal Cancer • Oncology • Peritoneal Cancer

A Phase II Study of IMMU 130 in Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Immunomedics, Inc.; N=50 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Regulation of CEACAM5 and therapeutic efficacy of an anti-CEACAM5-SN38 antibody-drug conjugate in neuroendocrine prostate cancer. (PubMed, Clin Cancer Res) - "Our findings provide insights into the scope and regulation of CEACAM5 expression in prostate cancer and strong support for clinical studies of labetuzumab govitecan for NEPC."

Clinical • Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Sacituzumab govitecan demonstrates metastatic urothelial cancer benefit | Yohann Loriot (YouTube) - "Yohann Loriot discusses the TROPHY-U-01 trial update confirming that sacituzumab govitecan is active in heavily pretreated metastatic urothelial cancer (5:26)."

Video

[VIRTUAL] Multimodal Fluorescence-guided Surgery of Colorectal Peritoneal Metastases: A Phase I/II Clinical Trial (SSO 2020) - " In this single arm intervention study patients will receive an intravenous dose of the CEA-targeting tracer 111In-DOTA-labetuzumab-IRDye800CW... We show that CEA-targeted multimodal imaging in patients with colorectal peritoneal carcinomatosis is feasible and safe in the first 7 patients. The phase I is expected to reach completion in December 2019."

Clinical • P1/2 data • Colorectal Cancer • Fibrosis • Gastrointestinal Cancer • Oncology • Peritoneal Cancer • Solid Tumor

Impact of Different Selectivity between Soluble and Membrane-bound Forms of Carcinoembryonic Antigen (CEA) on the Target-mediated Disposition of Anti-CEA Monoclonal Antibodies. (PubMed, Drug Metab Dispos) - "In this study, we compared the effect of sCEA on the pharmacokinetics of 15-1-32 in mice with that of another anti-CEA monoclonal antibody, labetuzumab, showing less selectivity to mCEA than 15-1-32...Although the effect of soluble CEA on the serum concentration of 15-1-32 was very small, the clearance of 15-1-32 in CEA-positive tumor-bearing mice was still rapid, suggesting membrane-bound CEA also contributes to the clearance of anti-CEA antibodies. These results indicated that increasing selectivity to membrane-bound CEA is not enough to improve the pharmacokinetics of anti-CEA antibody."

Journal • Oncology

Dose Finding Study of Once or Twice Weekly IMMU-130 in Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: Immunomedics, Inc.; N=71 ➔ 0; Completed ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Labetuzumab may provide benefit in r/r metastatic colorectal cancer (Cancer Therapy Advisor) - P1/2, N=86; NCT01605318; Sponsor: Immunomedics; "After labetuzumab treatment, 38% of patients experienced tumor and plasma carcinoembryonic antigen reduction from baseline. Forty-two patients achieved stable disease and 1 patient achieved a partial response with a sustained response for more than 2 years. Median progression-free survival was 3.6 months and overall survival was 6.9 months."

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Immunomedics: Q2 FY 2016 Results (Immunomedics) - Anticipated end of P2 meeting with FDA for discussing the page three protocol design in metastatic colorectal cancer in December 2016

Anticipated FDA event • Colorectal Cancer • Oncology

Immunomedics: Q3 FY 2015 Results (Immunomedics) - Anticipated data from P2 trial (NCT01915472) in metastatic CRC at ASCO 2015 on June 2

Anticipated P2 data • Colorectal Cancer • Oncology

IMMU-130: "Median PFS of 4.0 months and median OS of 6.7 months in 23 patients with prior treatment with regorafenib" (Immunomedics) - Corporate Presentation

P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Immunomedics: Company Presentation (Immunomedics) - “IMMU-130 in Metastatic Colorectal Cancer”; “Promising activity in metastatic CRC previously treated with irinotecan therapy”; “Acceptable safety profile in heavily pretreated patients”; “Dose-limiting neutropenia (G3 and G4 = 10%)”; “Minimal diarrhea (G3 = 3%)”; “Best Response Results”

P1/2 data • Colorectal Cancer • Oncology

Immunomedics: Corporate Presentation (Immunomedics) - "IMMU-130: Efficacy in Metastatic Colorectal Cancer: Median PFS of 3.9 months and median OS of 6.7 months in 20 patients with prior treatment with regorafenib, bevacizumab, 5-fluorouracil, irinotecan and oxaliplatin-containing chemotherapies"

P1/2 data • Colorectal Cancer • Oncology

Labetuzumab govitecan (IMMU-130), an anti-CEACAM5/SN-38 antibody-drug conjugate, is active in patients (pts) with heavily pretreated metastatic colorectal cancer (mCRC): Phase II results (AACR 2016) - P2, N=86; NCT01605318; Sponsor: Immunomedics; "The QW regimen appeared superior based on disease control rate, PFS, and OS. Eleven pts (78%) at 10 mg/kg QW in 21-day cycles (N=19) had stable disease compared to 7 pts (44%) at 6 mg/kg BIW (N=19). One pt had a confirmed PR (88% shrinkage) at 6 mg/kg BIW dose, and then maintained PR at 8 mg/kg QW for 3-wk cycles over 2 yrs. Median PFS at 10 mg/kg QW was 4.6 mos compared to 3.7 mos at 6 mg/kg BIW (3-wk cycles). Median OS at 10 mg/kg QW was 9.3 mos compared to 7.4 mos at 6 mg/kg BIW."

P2 data • Colorectal Cancer • Oncology

Immunomedics: Company Presentation (Immunomedics) - Anticipated presentation of updated data from P2 trial (NCT01605318) in metastatic colorectal cancer in H1 2016

Anticipated P2 data • Colorectal Cancer • Oncology