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

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With Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=92 | Terminated | Sponsor: Gilead Sciences | Withdrawn ➔ Terminated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

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

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

A new anti-CEA-SN-38 antibody-drug conjugate (ADC), IMMU-130, is active in controlling metastatic colorectal cancer (mCRC) in patients (pts) refractory or relapsing after irinotecan-containing chemotherapies: Initial results of a phase I/II study (ASCO 2015) - Presentation time: Tuesday, Jun 2; 9:12 AM - 9:24 AM; Abstract #2505; P1/2, N=66; NCT01605318; Sponsor: Immunomedics; "The dose selected for further study was 10 mg/kg weekly or 6 mg/kg biw. No pt developed antibodies to the conjugate. Tumor reductions were seen in 23/66 (35%) pts, including one PR with 88% best tumor shrinkage still being treated for 52+ weeks, 6 pts with 20-30% tumor reductions, and 16 pts with 0-20% tumor reductions."

P1/2 data • Colorectal Cancer • Oncology

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

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: 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

Immunomedics announces pricing of public offering of common stock (GlobeNewswire) - "Immunomedics, Inc...announced the pricing of an underwritten public offering of 14,736,860 shares of its common stock at a public offering price of $28.50 per share, representing gross proceeds of approximately $420 million...Immunomedics intends to use the net proceeds from this offering primarily to support the commercial launch of Trodelvy™ in the United States in metastatic triple-negative breast cancer, continue to expand the clinical development programs for Trodelvy, invest in the broader clinical development of the platform (including IMMU-130 and IMMU-140)..."

Financing • Breast Cancer • Oncology • Solid Tumor

Immunomedics Announces Pricing of Public Offering of Common Stock (GlobeNewswire) - "Immunomedics intends to use the net proceeds from this offering primarily to accelerate commercial launch readiness, pending FDA approval, of sacituzumab govitecan in the United States in metastatic triple-negative breast cancer, continue to expand the clinical development programs for sacituzumab govitecan, invest in the broader clinical development of the platform (including IMMU-130 and IMMU-140), continued scale-up of manufacturing and manufacturing process improvements, as well as for working capital and general corporate purposes."

Financing