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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer, Ovarian Cancer
• Intervention / Treatment: Drug: DNIB0600A

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Oncologia
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute - Pima Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital at Yale New Haven
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Inst.
  • Texas
    • Dallas, Texas, United States, 75390
      • Univ of Texas SW Medical Ctr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose Escalation Cohort (DNIB0600A); 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; Several dose levels will be evaluated for DNIB0600A administered via IV infusion on Day 1 of each 21-day cycle until disease progression.
EXPERIMENTAL: Expansion Cohort (DNIB0600A); Participants will receive 2.4 mg/kg, by IV infusion, of DNIB0600A q3w for up to 26 cycles.	Drug: DNIB0600A; Several dose levels will be evaluated for DNIB0600A administered via IV infusion on Day 1 of each 21-day cycle until disease progression.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2011
• Primary Completion (ACTUAL): June 3, 2016
• Study Completion (ACTUAL): June 3, 2016

Study Registration Dates

• First Submitted: May 26, 2011
• First Submitted That Met QC Criteria: May 31, 2011
• First Posted (ESTIMATE): June 2, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 7, 2017
• Last Update Submitted That Met QC Criteria: June 5, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: DNB4987g; GO27767 (OTHER: Hoffmann-La Roche); 2014-000527-25 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No