Animal model or human cells: efficacy evidence for approved ADCs

“In vivo anti-tumour activity of brentuximab vedotin was demonstrated in three xenograft transplant models derived from human HL and ALCL cell lines.”

“The in vivo antitumor activity of inotuzumab ozogamicin was evaluated in xenograft and systemically disseminated ALL mouse models.”

“Four in vivo studies were performed with datopotamab deruxtecan (Dato-DXd) administered intravenously to nude mouse xenograft models of human pancreatic cancer, non-small cell lung cancer (NSCLC) and breast cancer, with the two latter being in line with the sought indications.”

“In vivo activity was evaluated against two patient-derived xenograft (PDX) models of BPDCN using immunocompromised (NSG) mice and weekly intravenous injections beginning 24 hours after FcR blockade for three weeks.”

“In vivo, mirvetuximab soravtansine delayed tumor growth and caused tumor regression in several ovarian cancer xenograft mouse models when mice were administered a single IV dose of mirvetuximab soravtansine containing antibody doses as low as 1.2 mg/kg and DM4 dose of 25 µg/kg.”

“In vivo, telisotuzumab vedotin exhibited antitumor activity in c-Met-positive NSCLC cell line-derived xenograft mouse models and an NSCLC patient-derived xenograft model.”

“The anti-tumor activity of DS-8201a was evaluated in several mouse models of breast cancer. In a mouse xenograft model of HER2-positive breast cancer, the activity of a single dose of 10 mg/kg DS-8201a or MAAL-9001 was evaluated 13 days after inoculation of KPL-4 cells to female CAnN.Cg-Foxn1nu/CrlCrlj nude mice”

“Trastuzumab-MCC-DM1 caused tumor growth inhibition in all three models in the dose range of 3 to 31 mg/kg, depending on the model.”

“Anti-tumor activity of trastuzumab emtansine was evaluated in three independent animal models of HER2-positive human cancers (not formally reviewed). Two of these are xenograft models using human tumor cell lines.”

“In vivo antitumor effects of CMA-676 were studied in an HL-60 xenograft tumor model. CMA-676 showed a dose-response effect with >80% inhibition of tumor growth at doses between 0.8 and 2.4 mg/m2 NAc-gamma calicheamicin DMH equivalents”

“In vivo, enfortumab vedotin administration to AG-B1 and AG-B8 (cells expressing human Nectin-4) patient-derived human bladder cancer xenograft mouse models resulted in >75% tumor growth inhibition relative to the unconjugated antibody and the control (5% dextrose).”

“Polatuzumab vedotin demonstrated anti-tumor activity in vitro in CD79b expressing human Burkitt lymphoma (Ramos) cells (IC50 = 0.071 nM) and in vivo in DLBCL and human B-cell lymphoma mouse xenograft models.”

“The anti-tumour activity of polatuzumab Ab, polatuzumab vedotin and of the surrogate Ab and ADC was compared in a murine xenograft model with the BJAB Burkitt lymphoma transfectant cell line which expresses comparable amounts of human CD79b and recombinant Cynomolgus CD79b.”

“In vivo, anti-tumor activity and/or tumor regression was seen in cervical cancer patient derived xenograft (PDX) models when mice were administered tisotumab vedotin at 4 mg/kg twice in the first week of study via intravenous dosing.”

“Tisotumab did not bind to mouse, rat, rabbit, pig, or dog TF.”

“Primary pharmacology was tested in murine xenograft models bearing human Trop-2 expressing tumors.”

“Despite approx. 80% sequence homology at the protein level between human and rodent Trop-2, hRS7 did not bind to mouse and rat Trop-2.”

“The in vivo activity of ADCT‐402 was evaluated in immunodeficient mice subcutaneously (SC) xenografted with the CD19 positive human Ramos or Daudi Burkitt’s lymphoma cell lines or with the CD19 positive human DLBCL cell line, WSU‐DLCL2 (Study No. ADCT‐402_R_007_R).”

“The monoclonal antibody (mAb) component of loncastuximab tesirine, RB4v1.2, is selective for human CD19 and not cross‐reactive with CD19 from any nonclinical species.”