Eligible participants are adults (≥18 years) with locally advanced/metastatic solid tumors (specific sarcoma subtypes, NSCLC, or AXL-amplified tumors) refractory to standard therapy, measurable disease per RECIST 1.1, ECOG 0-1, and adequate organ function. Key exclusions include active CNS metastases (unless treated and stable ≥4 weeks), significant third-space fluid accumulation, recent infections requiring IV therapy, chronic diarrhea (CTCAE Grade 2+), or experimental medication use within 14 days prior to treatment initiation.

As of 04 December 2023, 18 sarcoma patients (15 [83%], soft tissue sarcoma [STS] and 3 [17%] bone sarcoma), unselected for AXL expression, with a median number of 3 prior lines of therapy (1-10), were enrolled in 4 different dose cohorts: 7.5mg, 11mg, 13mg and 15mg. Reasons for treatment discontinuation were disease progression (10 pts [55.6%]), adverse events (3 pts [16.7%]) and consent withdrawal (2 pts [11.1%]). Treatment emergent adverse events (TEAE) were seen in 17 pts (94.4%). Most common TEAE (all grades and relationship [≥20%]) were palmar-plantar erythrodysesthesia syndrome (7 pts [38.9%]); anemia (6 pts [33.3%]); rash maculopapular (5 pts [27.8%]); cheilitis and constipation (4 pts each [22.2%]). TEAE≥grade 3 were seen in 9 pts (50%). Most common TEAE≥grade 3 (≥10%) were GGT increase (2 pts [11.1%]). Two dose limiting toxicities were seen: cheilitis grade 2 and grade 3 at 15mg and 13mg respectively. Cutaneous reactions, all grades, are more prominent in higher doses. Maximum tolerated dose (MTD) has not been established.

Efficacy is measured by overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) over 2 years. Pharmacokinetic analysis includes serum concentration measurements of ADCT-601 components (total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199) with parameters like Cmax, Tmax, AUC, and half-life, alongside immunogenicity assessment through anti-drug antibody (ADA) responses and titers.

Eligible participants are adults (≥18 years) with locally advanced/metastatic solid tumors (specific sarcoma subtypes, NSCLC, or AXL-amplified tumors) refractory to standard therapy, measurable disease per RECIST 1.1, ECOG 0-1, and adequate organ function. Key exclusions include active CNS metastases (unless treated and stable ≥4 weeks), significant third-space fluid accumulation, recent infections requiring IV therapy, chronic diarrhea (CTCAE Grade 2+), or experimental medication use within 14 days prior to treatment initiation.

As of 04 December 2023, 18 sarcoma patients (15 [83%], soft tissue sarcoma [STS] and 3 [17%] bone sarcoma), unselected for AXL expression, with a median number of 3 prior lines of therapy (1-10), were enrolled in 4 different dose cohorts: 7.5mg, 11mg, 13mg and 15mg. Reasons for treatment discontinuation were disease progression (10 pts [55.6%]), adverse events (3 pts [16.7%]) and consent withdrawal (2 pts [11.1%]). Treatment emergent adverse events (TEAE) were seen in 17 pts (94.4%). Most common TEAE (all grades and relationship [≥20%]) were palmar-plantar erythrodysesthesia syndrome (7 pts [38.9%]); anemia (6 pts [33.3%]); rash maculopapular (5 pts [27.8%]); cheilitis and constipation (4 pts each [22.2%]). TEAE≥grade 3 were seen in 9 pts (50%). Most common TEAE≥grade 3 (≥10%) were GGT increase (2 pts [11.1%]). Two dose limiting toxicities were seen: cheilitis grade 2 and grade 3 at 15mg and 13mg respectively. Cutaneous reactions, all grades, are more prominent in higher doses. Maximum tolerated dose (MTD) has not been established.

Efficacy is measured by overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) over 2 years. Pharmacokinetic analysis includes serum concentration measurements of ADCT-601 components (total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199) with parameters like Cmax, Tmax, AUC, and half-life, alongside immunogenicity assessment through anti-drug antibody (ADA) responses and titers.

Eligible patients must be &ge;18 years with locally advanced/metastatic solid tumors (including breast, colorectal, NSCLC, and ovarian cancers) refractory to standard therapy, measurable disease per RECIST 1.1, ECOG 0-1, and adequate organ function. Key exclusions include active autoimmune/CNS diseases, uncontrolled comorbidities, recent anticancer therapy (<14 days), QTcF >480 ms, pregnancy, or live vaccines. Contraception is required during and for 16 weeks post-treatment.

As of data cutoff (April 12, 2019), 8 pts were treated at doses of 50-100 ug/kg. The median (range) age was 70 (46-77) years. Pathological subtypes enrolled are colorectal cancer (4 pts) and chondrosarcoma, head and neck carcinoma, ovarian carcinoma, and esophageal carcinoma (1 pt each). Six pts had received ≥4 previous lines of therapy. One pt treated at 100 ug/kg had a dose-limiting toxicity of grade 3 hematuria, which resulted in hospitalization and was possibly related to ADCT-601. The most common treatment-emergent adverse events, regardless of relationship to ADCT-601, were abdominal pain, erythema, fatigue, peripheral edema, and maculopapular rash (each occurring in 2 pts). The following 4 pts had undergone disease assessment at data cutoff: 1 pt (chondrosarcoma) had a partial response, 1 pt (head and neck carcinoma) had stable disease, and 2 pts (ovarian carcinoma and esophageal carcinoma) had progressive disease.

The study evaluates safety by assessing dose-limiting toxicities (DLTs) during the first treatment cycle (21-42 days depending on dosing schedule) and determines the maximum tolerated dose (MTD) through monitoring adverse events (AEs), serious adverse events (SAEs), and dose modifications over a 2-year follow-up period with treatment cycles every 3-6 weeks.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

Eligible participants must have histologically confirmed neuroendocrine neoplasms or adrenocortical carcinoma (ACC) with measurable disease (RECIST 1.1), prior standard therapy failure, ECOG &le;2, and adequate organ function. Exclusions include recent anticancer treatments (within 4 weeks), active infections, uncontrolled autoimmune diseases, QTcF &ge;480 ms, pregnancy, or live vaccines within 30 days. Contraception is required during and post-treatment (9.5 months for females, 6.5 months for males).

Safety evaluations include monitoring AEs through 30 days post-treatment, while efficacy is assessed via overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) over 5 years. Pharmacokinetic (PK) analysis measures PBD-conjugated antibody, total antibody, and unconjugated warhead SG3199 for up to 2 years, alongside immunogenicity testing for anti-drug antibodies (ADAs).