Recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 11); and had an Eastern Cooperative Oncology Group performance status of 0 or 1.

OrR of all patients=15.65% (23/147, 95% Cl 10.20-22.00), ORR of Bladder cancer=26.67% (4/15, 95% Cl 7.80-55.10), ORR of Cervical cancer=26.47% (9/34, 95% Cl 12.90-44.40), ORR of Endometrial cancer=7.14% (1/14, 95% Cl 0.20-33.90), ORR of Oesophageal cancer=13.33% (2/15, 95% Cl 1.70-40.50), ORR of NSCLC=13.33% (2/15, 95% Cl 1.70-40.50), ORR of Ovarian cancer=13.89% (5/36, 95% Cl 4.70-29.50).

TF-positive patient-derived xenograft (PDX) models were performed in athymic nude mice to evaluate the efficacy of the ADCs in vivo. Study animals were implanted unilaterally on the left flank with tumor fragments. Animals were randomized and treated as indicated in the figures. Animals were removed from study and euthanized once tumor size reached 1,200 mm³ or skin ulceration was evident. In addition, the MTV curve for the treatment group in question was no longer shown once an animal was removed from study due to size TGI and statistical analyses were conducted in the same manner as for the CDX studies. The CR and PR response definitions were as follows for the PDX studies: a PR responder had a MTV 30% of MTV at day 1 for two consecutive measurements; a CR responder had an undetectable MTV for two consecutive measurement IHC analisys: Formalin-fixed paraffin-embedded (FFPE) tissues were sectioned at 4-m thickness and mounted onto positive-charged glass slides The tissue sections were stained with the anti-TF antibody HTF-1 ADC treatment started on day 1 after animals with a tumor size of approximately 190 mm³ The model dosed weekly at 25 mg/kg for 3 weeks.

TF-positive patient-derived xenograft (PDX) models were performed in athymic nude mice to evaluate the efficacy of the ADCs in vivo. Study animals were implanted unilaterally on the left flank with tumor fragments. Animals were randomized and treated as indicated in the figures. Animals were removed from study and euthanized once tumor size reached 1,200 mm³ or skin ulceration was evident. In addition, the MTV curve for the treatment group in question was no longer shown once an animal was removed from study due to size TGI and statistical analyses were conducted in the same manner as for the CDX studies. The CR and PR response definitions were as follows for the PDX studies: a PR responder had a MTV 30% of MTV at day 1 for two consecutive measurements; a CR responder had an undetectable MTV for two consecutive measurement IHC analisys: Formalin-fixed paraffin-embedded (FFPE) tissues were sectioned at 4-m thickness and mounted onto positive-charged glass slides The tissue sections were stained with the anti-TF antibody HTF-1 ADC treatment started on day 1 after animals with a tumor size of approximately 210 mm³ The model dosed weekly at 5 mg/kg for 2 weeks.

TF-positive patient-derived xenograft (PDX) models were performed in athymic nude mice to evaluate the efficacy of the ADCs in vivo. Study animals were implanted unilaterally on the left flank with tumor fragments. Animals were randomized and treated as indicated in the figures. Animals were removed from study and euthanized once tumor size reached 1,200 mm³ or skin ulceration was evident. In addition, the MTV curve for the treatment group in question was no longer shown once an animal was removed from study due to size TGI and statistical analyses were conducted in the same manner as for the CDX studies. The CR and PR response definitions were as follows for the PDX studies: a PR responder had a MTV 30% of MTV at day 1 for two consecutive measurements; a CR responder had an undetectable MTV for two consecutive measurement IHC analisys: Formalin-fixed paraffin-embedded (FFPE) tissues were sectioned at 4-m thickness and mounted onto positive-charged glass slides The tissue sections were stained with the anti-TF antibody HTF-1 ADC treatment started on day 1 after animals with a tumor size of approximately 140 mm³ The model dosed weekly at 4 mg/kg for 3 weeks.

To evaluate ADC cytotoxicity, cells were plated in 384-well plates Anti-TF antibodies conjugated to MC-vc-PAB-MMAE were serially diluted as shown Plates were incubated for 3 days, followed by lysis in CTG assay reagent For each ADC, the IC50 and its associated 95% confidence interval (95% CI) were calculated Titrations of the TF-specific ADCs were added to A431 cells, with a 72-hour incubationThis treatment resulted in efficacious cell killing.

To evaluate ADC cytotoxicity, cells were plated in 384-well plates Anti-TF antibodies conjugated to MC-vc-PAB-MMAE were serially diluted as shown Plates were incubated for 3 days, followed by lysis in CTG assay reagent For each ADC, the IC50 and its associated 95% confidence interval (95% CI) were calculated Titrations of the TF-specific ADCs were added to A431 cells, with a 4-hour incubation followed by removal of excess ADC and culture for another 68 hours This treatment resulted in efficacious cell killing.