samrotamab vedotin (ABBV-085) / AbbVie - LARVOL DELTA

Response of C4.4A-positive patient-derived xenograft models of ESCC, HNSCC and bladder cancer to BAY1129980, a C4.4A-targeted antibody drug conjugate (AACR 2017) - P1; "Finally, both bladder models tested were sensitive to treatment, with a transient response seen in BL0597 (41%) and a strong and complete tumor growth control in BL5001 (93%,) which was superior to cisplatin. In summary, these data support further exploration of the potential of BAY 1129980 in HNSCC, ESCC and bladder cancer in addition to NSCLC. A Phase 1 clinical trial of BAY 1129980 is ongoing (NCT02134197)."

Biosimilar • Bladder Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Urothelial Cancer

First-in-human phase 1 study of ABBV-085, an antibody-drug conjugate (ADC) targeting LRRC15, in sarcomas and other advanced solid tumors. (ASCO 2019) - P1; "ABBV-085 was well tolerated with durable PR observed in pts with advanced sarcomas. Clinical trial information: NCT02565758"

P1 data • Oncology • Sarcoma • Solid Tumor

Exploiting LRRC15 as a novel therapeutic target in cancer. (PubMed, Cancer Res) - "This review focuses on the role of LRRC15 in cancer, including clinical trials involving LRRC15-targeted therapies, such as the ABBV-085 ADC for patients with LRRC15-positive tumors. This review spans perceived knowledge gaps and highlights the clinical avenues that need to be explored to provide better therapeutic outcomes in patients."

Journal • Brain Cancer • Fibrosis • Gastrointestinal Cancer • Glioblastoma • Hepatology • Melanoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • LRRC1

Targeting LRRC15 inhibits metastatic dissemination of ovarian cancer. (PubMed, Cancer Res) - "Furthermore, treatment of 3D-spheroid cultures of LRRC15-positive patient-derived ascites with ABBV-085 reduced cell viability. Overall, these data uncover a role for LRRC15 in promoting OC metastasis and suggest a novel and promising therapy to target OC metastases."

Journal • Colorectal Cancer • Oncology • Ovarian Cancer • Solid Tumor • LRRC1

First-in-Human Phase 1 Study of ABBV-085, an Antibody-Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors. (PubMed, Clin Cancer Res) - P1 | "ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted."

Journal • P1 data • Fatigue • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

[VIRTUAL] Stromal Targeting Antibody-Drug Conjugates – Learnings from ABBV-085 (PEGS 2021) - "Findings from ABBV-085 which targets the stromal antigen LRRC15 which is highly expressed on cancer associated fibroblasts (CAFs) in the tumor microenvironment, will be discussed. Preclinical and Phase 1 findings will be summarized, with a view to highlighting challenges and opportunities for targeting stromal antigens with antibody-drug conjugates."

Oncology • CAFs

ABBV-085, antibody-drug conjugate targeting LRRC15, is effective in osteosarcoma: A report by the Pediatric Preclinical Testing Consortium. (PubMed, Mol Cancer Ther) - "Response correlated with LRRC15 expression. ABBV-085's antitumor activity against osteosarcoma PDX suggests LRRC15 may be a rational target for pursuing clinical trials in patients with this disease."

Journal • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

LRRC15 Targeting in Soft-Tissue Sarcomas: Biological and Clinical Implications. (PubMed, Cancers (Basel)) - "We provide the first preclinical evidence that LRRC15 targeting with an antibody-drug conjugate is a promising strategy in LRRC15-positive STS. ABBV-085 is being evaluated in an ongoing clinical trial in STS and other malignancies."

Clinical • Journal

LRRC15 is a novel mesenchymal protein and stromal target for antibody-drug conjugates. (PubMed, Cancer Res) - "...ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate (ADC) directed against LRRC15, and it demonstrated robust preclinical efficacy against LRRC15 stromal-positive/cancer-negative, and LRRC15 cancer-positive models as a monotherapy, or in combination with standard-of-care therapies...ABBV-085's unique mechanism of action relied upon the cell-permeable properties of MMAE to preferentially kill cancer cells over LRRC15-positive CAF while also increasing immune infiltrate (e.g., F4/80+ macrophages) in the tumor microenvironment. In summary, these findings validate LRRC15 as a novel therapeutic target in multiple solid tumor indications and support the ongoing clinical development of the LRRC15-targeted ADC ABBV-085."

Journal

ABBV-085, an Antibody Drug Conjugate, in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=85; Completed; Sponsor: AbbVie; Active, not recruiting ➔ Completed

Trial completion