Combination therapy with Teliso-V plus nivolumab was well tolerated in patients with c-Met-+NSCLC with limited antitumor activity. The ORR was 7.40% (95% CI: 0.90-24.30), with two patients (PD-L1+, n =1; PD-L1-, n=1) having a confirmed PR.Overall, 66.67% of patients (16 of 24) had evidence of tumor size reduction; three (12.5%) reported a greater than 30% reduction in target lesion. The overall median PFS (95% CI) was 7.20 months (3.30-8.90); 7.20 months(1.50-not reached [NR]) for PD-L1 patients, 4.50 months(1.50-NR) for PD-L1- patients, and NR (2.00-NR) for PD-L1-unk patients. The objective response rate was 7.40%, with two patients having a confirmed partial response. Overall median progression-free survival was 7.20 months.

For EGFR-M+ patients (n = 28), ORR was 32.14% (9/28; 95% CI, 15.90 to 52.40), with one CR (3.57%) and eight PR (28.57%). DCR was 85.71% (24/28; 95% CI, 67.30 to 96.00) and median PFS was 5.90 months (95% CI, 2.80 to NR). Median PFS was 3.70 months (95% CI, 1.40 to NR) for T790M+ patients, compared with 6.80 months (95% CI, 4.30 to NR) for non-T790M+ patients. Of EGFR-M+ patients, those who were c-Met high (n = 15) had an ORR of 52.60%. Median PFS was 6.80 months for non-T790M+ and for those whose T790M status was unknown, versus 3.70 months for T790M+.

Eligibility requires c-Met+ SCCA with no prior immune checkpoint inhibitor (anti-PD-1/PD-L1/CTLA-4) or autoimmune disease (exceptions: vitiligo, stable endocrine disorders). Exclusions: active HBV/HIV, chronic HCV, interstitial lung disease, NYHA Class III/IV cardiac conditions, recent corticosteroids (>10mg prednisone/day), or allergies to nivolumab/ipilimumab. Cardiac dysfunction (CHF/MI within 6 months) mandates cardiology evaluation. PRO questionnaires (English) are mandatory pre-registration.

Secondary endpoints evaluate immunotherapy-exposed/relapsed c-Met+ SCCA: investigator-assessed progression-free survival (IA-PFS; time to progression/symptomatic deterioration/death), overall survival (OS; time to death), and ORR per RECIST 1.1 over 3 years. Duration of response (DoR; time from initial response to progression/death) is also measured.

Eligibility requires c-Met+ SCCA with no prior immune checkpoint inhibitor (anti-PD-1/PD-L1/CTLA-4) or autoimmune disease (exceptions: vitiligo, stable endocrine disorders). Exclusions: active HBV/HIV, chronic HCV, interstitial lung disease, NYHA Class III/IV cardiac conditions, recent corticosteroids (>10mg prednisone/day), or allergies to nivolumab/ipilimumab. Cardiac dysfunction (CHF/MI within 6 months) mandates cardiology evaluation. PRO questionnaires (English) are mandatory pre-registration.

Secondary endpoints evaluate immunotherapy-exposed/relapsed c-Met+ SCCA: investigator-assessed progression-free survival (IA-PFS; time to progression/symptomatic deterioration/death), overall survival (OS; time to death), and ORR per RECIST 1.1 over 3 years. Duration of response (DoR; time from initial response to progression/death) is also measured.

Eligible participants must have c-Met+ locally advanced/metastatic non-squamous EGFR-wildtype NSCLC (&le;2 prior systemic therapies including &le;1 cytotoxic chemotherapy line) with ECOG 0-1. Exclusions include recent lung radiation (<6 months), adenosquamous histology, ILD/pneumonitis history (no evidence on screening imaging for Ireland sites), active infections (HIV/HBV/HCV - specific to France/CZ sites), and unresolved Grade&ge;2 toxicities (except alopecia/anemia). Stable CNS metastases post-definitive therapy are permitted.

Eligible patients have advanced NSCLC (ECOG 0-2) with measurable disease and adequate organ function. Exclusions: recent lung radiation (<6 months), uncontrolled CNS metastases, ILD/pneumonitis history, unresolved Grade&ge;2 toxicities, major surgery within 21 days, or active COVID-19. Combination-specific exclusions apply (e.g., QTc>470ms for osimertinib arm; autoimmune disease/immunosuppressants for nivolumab arm).

Eligible participants must have c-Met-overexpressing non-squamous NSCLC (confirmed by AbbVie's IHC assay), actionable gene alterations (if applicable), measurable disease (RECIST v1.1), ECOG 0-1, and &le;1 prior cytotoxic chemotherapy line in advanced/metastatic setting. Exclusions include untreated CNS metastases, prior c-Met/EGFR-targeted therapy, docetaxel exposure, idiopathic pulmonary fibrosis, unresolved Grade &ge;2 toxicities (except alopecia/anemia), major surgery within 21 days, or protocol-specified comorbidities. Stable brain metastases post-treatment are allowed if asymptomatic and off steroids (&le;10mg prednisone/day).

Additional efficacy measures comprise objective response rate (ORR) and duration of response (DoR) per BICR (up to 58.25 months), alongside quality-of-life changes (EORTC QLQ-C30) over 12 weeks, assessing physical function and global health status on a 0-100 scale where higher scores indicate better functioning/quality of life or worse symptom burden.

Eligible participants must have MET-amplified non-squamous NSCLC (central lab-confirmed), measurable disease (RECIST v1.1), ECOG 0-1, and prior adjuvant/neoadjuvant therapy completed &ge;6 months pre-enrollment. Exclusions include actionable EGFR/ALK/ROS1/BRAF alterations, prior metastatic NSCLC systemic therapy (except &le;1 chemotherapy cycle), unresolved Grade &ge;2 toxicities (excluding alopecia/anemia), major surgery within 21 days, or protocol-specified comorbidities (e.g., active pneumonitis). Stable CNS metastases post-treatment are permitted.

Eligible participants must have EGFR-mutated (del19/L858R &plusmn;T790M), c-Met-overexpressing non-squamous NSCLC (IHC-confirmed), ECOG 0-1, measurable disease (RECIST v1.1), and progression on prior third-generation EGFR TKI (e.g., osimertinib). Exclusions include actionable ALK/ROS1/BRAF alterations, prior metastatic chemotherapy (except limited platinum pre-TKI), unresolved Grade &ge;2 toxicities (excluding alopecia/anemia), major surgery within 21 days, active pneumonitis, or protocol-specified comorbidities (e.g., uncontrolled infections, &ge;Grade 2 edema/neuropathy). Stable CNS metastases post-definitive therapy are permitted if asymptomatic for &ge;4 weeks.

The study evaluates progression-free survival (PFS) both in participants without CNS metastases and in the overall population, defined as time from randomization to radiographic progression (RECIST v1.1) or death. Overall response (OR) and duration of response (DoR) are similarly assessed, with OR defined as confirmed complete (CR) or partial response (PR), and DoR measuring time from response to progression or death.

Eligible participants must have c-Met-overexpressing NSCLC (IHC-confirmed), ECOG 0-1, measurable disease (RECIST v1.1), and &le;1 prior cytotoxic chemotherapy line. Exclusions include actionable EGFR mutations, prior c-Met-targeted ADCs/docetaxel, active pneumonitis, unresolved Grade&ge;2 toxicities (excluding alopecia/anemia), major surgery within 21 days, or protocol-specified comorbidities (e.g., &ge;Grade 2 edema/neuropathy, uncontrolled infections). Stable CNS metastases post-therapy are permitted if asymptomatic.

Safety endpoints include treatment-emergent adverse events (AEs) (any-grade/Grade≥2), specifically interstitial lung disease (ILD), peripheral neuropathy, and ocular surface disorders (corneal epitheliopathy) over 3 years, along with AEs leading to treatment discontinuation or Grade 5 (fatal) events. Efficacy measures include objective response (OR: CR/PR per RECIST v1.1) and duration of response (DoR) assessed by blinded independent central review (BICR).

Pharmacokinetic analyses measure telisotuzumab vedotin conjugate (serum) and MMAE payload (plasma) concentrations over 26 weeks, alongside antidrug antibody (ADA/nADA) incidence. Patient-reported outcomes assess treatment tolerability via PRO-CTCAE (0-4 scale) and FACT-G GP5 item. Secondary endpoints include PFS (time to progression/death) and OS (time to death) over 3 years.

Eligible participants must have histologically confirmed advanced solid tumors (ECOG 0-2) with measurable disease, archived tumor tissue, and adequate organ function. Exclusions: prior anticancer therapy within 21 days (7 days for herbal), uncontrolled brain metastases (eligible post-definitive therapy if asymptomatic without steroids/anticonvulsants for &ge;2 weeks), unresolved Grade&ge;2 toxicities (except alopecia/anemia), or major surgery within 21 days.

Eligible participants must have measurable disease of specified tumor types (HCC, PDAC, HNSCC etc.) and meet protocol-defined lab criteria. Key exclusions include prior anticancer therapy within 28 days, active ILD/pneumonitis, untreated CNS metastases, concurrent autoimmune disorders with pulmonary involvement, and unresolved Grade >1 toxicities from prior treatments.

Eligible participants must have ECOG PS 0-1, confirmed advanced/metastatic mCRC without BRAF V600E or dMMR+/MSI-H status, and measurable disease. Stage 2 requires c-Met protein expression (3+ intensity, &ge;10% tumor cells). Key exclusions include recent cardiac events, prior c-Met antibody/ADC therapy, ILD/pneumonitis history, unresolved toxicities (Grade >1), untreated CNS metastases, or concurrent autoimmune/inflammatory lung disorders.

The study evaluates safety (AEs, vital signs, ECGs, lab abnormalities), pharmacokinetics (Cmax, Tmax, AUC, t1/2, ADC, unconjugated Top1 inhibitor), immunogenicity (ADAs/nADAs) and efficacy (OR, PFS, OS, DOR, DC) of ABBV-400 in Stage 1, with Stage 2 focusing on efficacy and patient-reported physical function/diarrhea/QoL via EORTC QLQ-C30 over 4 years.

Eligibility requires histologically confirmed advanced/metastatic non-squamous NSCLC (Part 1: &le;1 prior systemic therapy; Part 2: treatment-naive with no actionable mutations), measurable disease per RECIST v1.1, documented PD-L1 status, and adequate organ function, excluding those with uncontrolled CNS metastases or active ILD/pneumonitis requiring steroids.

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).

The ability of bis-intercalating peptide free drugs and ADCs to inhibit proliferation of tumor cells in vitro was evaluated using the following cell lines: OVCAR-3 (ovarian, ATCC), SKOV-3 (ovarian, ATCC), IGROV-1 (ovarian, national research council of Canada (NRC)), OV-90 (ovarian, ATCC), OVKATE (Ovarian, Japanese Collection of Research Bioresources (JCRB) (JCRB1044)), JIMT-1 (breast, NRC), SK-BR-3 (breast, ATCC), T-47D (breast, ATCC), ZR-75-1 (breast, ATCC), MDA-MB-468 (breast, AddexBio), BT-20 (breast, ATCC), BT-474 (breast, NRC), MDA-MB-175 (breast, AddexBio), A549 (lung, collaborator), NCI-H226 (lung, NRC), NCI-H661 (lung, NRC), NCI-H1573 (lung, ATCC). NCI-H1563 (lung, ATCC), H358 (lung, collaborator), EBC-1 (lung, Xenotech), H1299 (lung, NRC), NCI-H292 (lung, ATCC), HCC817 (lung, ATCC), NCI-H441 (lung, ATCC), MIA-PaCa-2 (pancreatic, ATCC), BxPC-3 (pancreatic, ATCC), Panc-1 (pancreatic, ATCC), AsPC-1 (pancreatic, ATCC), JEG-3 (placenta, AddexBio), HT-29 (colon, ATCC). Cells cultured (per vendor instructions) in log-phase growth were detached by brief incubation in 0.05% trypsin and resuspended in respective culturing media at 20,000 cells/mL (except for ZR-75 cells, which were resuspended at 10,000 cells/mL). 50 uL/well (~1000 cells/well) were transferred to sterile tissue culture (TC)-treated 384-well plates (ThermoFisher Scientific, Catalogue # 164610) and incubated overnight at 37 °C with 5% CO2 to allow the cells to adhere to the plate surface. The next day, in a sterile, V-bottom, 96-well plate, test articles were titrated 1:3 in complete growth medium, creating a 10-point dose response titration with compounds at 3.5-times the desired final concentration. A total of 20 uL from each dilution was added to the 384-well plate containing the seeded cells, and these plates were incubated at 37 °C with 5% CO2 for 5 nights. Cell viability was quantified by first incubating with 15 uL/well of CellTiter-Glo (Promega, Catalogue # G7572) for 30 min and then measuring luminescence with a microplate luminometer (BioTek Synergy H1 Microplate Reader). IC50 values were determined by GraphPad Prism (GraphPad Software, Sand Diego, CA).