At active doses 1.80 mg/kg, partial responses were observed in four of 51 (7.84%) patients with NSCLC and 11 of 24 (45.83%) patients. In the NSCLC cohorts, PRs were seen in 1 of 4 (25.00%) at 1.80 mg/kg and in 3 of 45 (6.67%) patients at 2.40 mg/kg, mDoR=161 days. In PROC, PRs were seen at 1.80 mg/kg in one of two (50.00%), at 2.40 mg/kg in seven of 18 (38.89%), and at 2.80 mg/kg in three of four (75.00%) patients; mDoR=342 days.

The stratified PFS hazard ratio was 0.78 (95% CI,0.46-1.31; p=0.34) with a median PFS of 5.30 vs. 3.10 months (LIFA vs. PLD arm,respectively) in the ITT population, and 0.71 (95% CI,0.40-1.26; p=0.24) with a median PFS of 5.30 vs. 3.40 months (LIFA vs. PLD arm,respectively) in NaPi2bxhigh patients. The objective response rate (ORR) was 34.00% (95% CI,22.00-49.00%,LIFA) vs. 15.00% (95% CI, 7.00-28.00%,PLD) in the ITT population (p=0.03), and 36.00% (95% CI, 22.00-52.00%,LIFA) vs.14.00% (95% CI,6.00-27.00%,PLD) in NaPi2bxhigh patients (p=0.02).

Inclusion criteria: ECOG 0-1; histologically confirmed platinum-sensitive ovarian, peritoneal, or fallopian tube cancer or NSCLC with ≤2 prior regimens (additional targeted therapy permitted for EGFR/ALK mutations). NSCLC requires NaPi2b IHC 2+/3+. Exclusions: recent anti-tumor therapy/surgery, active infections, untreated CNS metastases, prior NaPi2b therapy, or specific contraindications for bevacizumab (e.g., uncontrolled hypertension, recent thrombosis).

Eligible patients must have ECOG 0-1, histologically confirmed advanced ovarian, peritoneal, or fallopian tube cancer refractory to platinum therapy, ≤2 prior regimens, adequate organ function, and contraception compliance. Exclusions include prior anthracycline/NaPi2b therapy, major surgery within 4 weeks, uncontrolled comorbidities, active infections, hepatitis/HIV, CNS metastases, pregnancy, NaPi2b deficiency, or severe hypersensitivity to monoclonal antibodies.

Secondary endpoints include objective response rate (ORR) and duration of response per RECIST v1.1, overall survival (OS), incidence of adverse events (AEs), and pharmacokinetic parameters such as AUC, Cmax, CL, t½, and Vss of DNIB0600A, along with anti-therapeutic antibody (ATA) formation. Assessments span from baseline up to 30 days post-treatment or longer, with detailed time points for PK analysis.

Inclusion criteria: ECOG 0-1; histologically confirmed platinum-sensitive ovarian, peritoneal, or fallopian tube cancer or NSCLC with ≤2 prior regimens (additional targeted therapy permitted for EGFR/ALK mutations). NSCLC requires NaPi2b IHC 2+/3+. Exclusions: recent anti-tumor therapy/surgery, active infections, untreated CNS metastases, prior NaPi2b therapy, or specific contraindications for bevacizumab (e.g., uncontrolled hypertension, recent thrombosis).

Outcomes included safety (AE incidence), pharmacokinetics (Cmax of DNIB0600A components), immunogenicity (ADA development), and efficacy (OR and DOR per RECIST v1.1). Key endpoints spanned up to 84 weeks, assessing tumor response dynamics-complete or partial shrinkage (≥30% reduction), stable disease, or progression (≥20% increase or new lesions)-while monitoring drug-related toxicities and immunologic reactions. Rigorous eligibility criteria balanced participant safety with disease relevance, excluding high-risk conditions or recent therapies to isolate investigational drug effects.

The study assessed adverse events (AEs) over approximately 2 years, defined as any unfavorable or unintended sign, symptom, or disease temporally linked to investigational medicinal product (IMP) use, irrespective of causality. Peak concentrations (Cmax) of DNIB0600A components-acMMAE, total antibody, and unconjugated MMAE-were evaluated on Day 21, alongside the percentage of participants developing anti-drug antibodies (ADAs) over 84 weeks, measuring baseline prevalence and post-baseline incidence. Objective response (OR) per RECIST v1.1 criteria, including complete response (disappearance of target lesions) and partial response (≥30% decrease in lesion diameters), was tracked for 84 weeks, along with duration of response (DOR), stable disease, and progression criteria (≥20% increase in lesion diameters or new lesions).

Inclusion criteria required an ECOG performance status of 0 or 1, histologic evidence of incurable locally advanced/metastatic disease (e.g., non-squamous NSCLC or platinum-resistant ovarian cancer), measurable disease, access to archival tumor samples, and contraception use for fertile participants. Exclusion criteria encompassed recent anti-tumor therapy, major surgery within 4 weeks, active infections, significant liver disease, untreated CNS metastases, oxygen dependency, uncontrolled comorbidities, and prior treatments (≤2 regimens for NSCLC expansion cohort). Pregnancy or breastfeeding also disqualified participation.

Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm³. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm³. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm³. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm³. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm³. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm³. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg qwk x 3.

Animals were randomized into treatment groups (n = 10) when the tumor target volume reached 100-150 mm³. Test articles were administered intravenously via tail vein injection. Mice received a single dose of either saline vehicle; XMT-1535 at 3 mg/kg; XMT-1536 (DAR 12.4) at 3 mg/kg; IgG1-Dolaflexin (DAR 18.1) at 3 mg/kg,or lifastuzumab vedotin (DAR 4.1) at 3 mg/kg. Tumors were measured twice per week. XMT-1536 and lifastuzumab vedotin were administered at a single dose of 3 mg/kg.