Safety and Pharmacokinetics of Escalating Doses of DNIB0600A in Participants With Non-Small Cell Lung Cancer (NSCLC) and Platinum Resistant Ovarian Cancer

Study Overview
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Brief Summary
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Study DNB4987g is a Phase I, multicenter, open label, dose-escalation study of DNIB0600A administered as a single agent by intravenous (IV) infusion every three weeks (q3w) to participants with non-squamous NSCLC or non-mucinous, platinum-resistant ovarian cancer. The study will be conducted in two cohorts: Dose-escalation cohort and Expansion cohort.

Official Title
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A Phase I, Open-Label Study of the Safety and Pharmacokinetics of Escalating Doses of DNIB0600A in Patients With Non-Small Cell Lung Cancer and Platinum-Resistant Ovarian Cancer

Conditions
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Non-Small Cell Lung Cancer, Ovarian Cancer

Intervention / Treatment
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* Drug: DNIB0600A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Histologic documentation of incurable, locally advanced or metastatic disease that has failed prior chemotherapy and for which no standard therapy exists, including the following: non-squamous NSCLC or non-mucinous and platinum-resistant ovarian cancer Availability and willingness to provide an adequate archival sample of tumor Measurable disease For fertile men or women of childbearing potential, documented willingness to use a highly effective means of contraception Exclusion Criteria: Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy within 4 weeks prior to study treatment Major surgical procedure within 4 weeks prior to study treatment Known active bacterial, viral, fungal, mycobacterial, or other infection (including human immunodeficiency virus [HIV] and atypical mycobacterial disease, but excluding fungal infections of the nail beds) Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis Untreated or active central nervous system (CNS) metastases Requirement for supplemental oxygen to carry out activities of daily living Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture For participants in the second NSCLC cohort expansion, not more than two prior regimens in the metastatic setting Pregnancy or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort (DNIB0600A)<br>Participants will receive IV infusions of DNIB0600A at doses ranging from 0.2 milligrams/kilogram (mg/kg) to 2.8 mg/kg q3w until dose-limiting toxicity (DLT) is reached, or up to 28 cycles. | Drug: DNIB0600A<br>* Several dose levels will be evaluated for DNIB0600A administered via IV infusion on Day 1 of each 21-day cycle until disease progression.<br>|
| Experimental: Expansion Cohort (DNIB0600A)<br>Participants will receive 2.4 mg/kg, by IV infusion, of DNIB0600A q3w for up to 26 cycles. | Drug: DNIB0600A<br>* Several dose levels will be evaluated for DNIB0600A administered via IV infusion on Day 1 of each 21-day cycle until disease progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs) | An AE is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of causality. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of DNIB0600A for Antibody-Conjugated Monomethyl Auristatin E (acMMAE), Total Antibody, and Unconjugated Monomethyl Auristatin E (MMAE) | Cmax is the peak concentration of a substance in blood serum. | Day 21 | 
| Percentage of Participants with Antibody Formation to DNIB0600A | Serum samples will be analyzed to assess the prevalence of anti-drug antibodies (ADAs) at baseline and the incidence of post-baseline ADAs in each treatment group. | Up to approximately 84 weeks | 
| Percentage of Participants with Objective Response (OR) | OR is defined as a complete or partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum on study. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression. | Up to approximately 84 weeks | 
| Duration of Objective Response (DOR) | OR is defined as a complete or partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum on study. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression. | Up to approximately 84 weeks |