A Study to Evaluate the Safety and Pharmacology of DNIB0600A in Participants With Platinum-Sensitive Ovarian Cancer or Non-Squamous Non-small Cell Lung Cancer

NCT01995188 | Completed Phase 1

• 1 other identifier: GO29006
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

Brief Summary

This open-label, multicenter, phase 1b study will evaluate the safety and pharmacokinetics of DNIB0600A in participants with platinum-sensitive ovarian cancer (PSOC) or Non-Squamous Non-small Cell Lung Cancer (NSCLC). The maximum tolerated dose of intravenously infused DNIB0600A in combination with carboplatin will be determined in escalating dose cohorts. The combination of DNIB0600A and carboplatin will then be evaluated with and without bevacizumab \[Avastin\] in three dose expansion cohorts.

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Dose-limiting Toxicities (DLTs)

  21 days

• Number of Participants with Adverse events (AE) and Serious Adverse Events (SAEs)

  Day 1 until 30 days after the last-infusion (up to approximately 3 years)

• Number of Participants with Anti-DNIB0600A Antibodies

  Pre-infusion (0 hour) at Day 1 of Cycle 1, 2, 3, 4 (each cycle of 21 days), 30 days after last infusion (up to approximately 3 years)

Secondary Outcomes (9)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] of DNIB0600A

  Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)

• Maximum Observed Plasma Concentration (Cmax)

  Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)

• Minimum Observed Plasma Trough Concentration (Cmin)

  Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)

• Systemic Clearance (CL)

  Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)

• Volume of Distribution at Steady State (Vss)

  Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)

Study Arms (4)

Dose Escalation Cohort: DNIB0600A+Carboplatin

EXPERIMENTAL

DNIB0600A at an initial dose of 1.2 milligrams per kilogram (mg/kg) will be administered via intravenous (IV) infusion further following a dose-escalation until DLT under consultation of the investigator in combination with Carboplatin fixed dose of area under the curve (AUC)=6 mg/milliliter(mL)\*minute (min) administered by IV infusion on Day 1 of a 21-day cycle.

Drug: Carboplatin; Drug: DNIB0600A

NSCLC Dose Expansion Cohort: DNIB0600A+Carboplatin

EXPERIMENTAL

Recommended phase 2 dose (RP2D) of DNIB0600A administered via IV infusion in combination with Carboplatin, AUC=6 mg/mL\*min administered via IV infusion on Day 1 of each 21-day cycle in participants with NSCLC until disease progression or death, whichever occurs first.

Drug: DNIB0600A

PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin

EXPERIMENTAL

RP2D of DNIB0600A administered via IV infusion in combination with AUC=6 mg/mL\*min administered via IV infusion on Day 1 of each 21-day cycle in participants with PSOC until disease progression or death, whichever occurs first.

Drug: Carboplatin; Drug: DNIB0600A

PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin+Bevacizumab

EXPERIMENTAL

RP2D of DNIB0600A administered via IV infusion in combination with Carboplatin, AUC=6 mg/mL\*min and Bevacizumab 15 milligrams per kilogram (mg/kg) administered via IV infusion on Day 1 of each 21-day cycle in participants with PSOC until disease progression or death, whichever occurs first.

Drug: Bevacizumab; Drug: Carboplatin; Drug: DNIB0600A

Interventions

Bevacizumab DRUG

Bevacizumab 15 milligrams per kilogram (mg/kg) administered via IV infusion on Day 1 of each 21-day cycle until disease progression or death, whichever occurs first.

Also known as: Avastin

PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin+Bevacizumab

Carboplatin DRUG

Carboplatin fixed dose of AUC=6 mg/mL\*min administered by IV infusion on Day 1 of each 21-day dose escalation and expansion cycles. Carboplatin will be administered for a maximum of 6 cycles or until disease progression or unacceptable toxicity, whichever is first.

Dose Escalation Cohort: DNIB0600A+Carboplatin; PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin; PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin+Bevacizumab

DNIB0600A DRUG

DNIB0600A at an initial dose of 1.2 mg/kg will be administered via IV infusion further following a dose-escalation until DLT under consultation of the investigator on Day 1 of 21 day dose-escalation cycle. RP2D will be administered further in dose-expansion for until disease progression or death, whichever occurs first.

Dose Escalation Cohort: DNIB0600A+Carboplatin; NSCLC Dose Expansion Cohort: DNIB0600A+Carboplatin; PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin; PSOC Dose Expansion Cohort: DNIB0600A+Carboplatin+Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
• Histologically documented epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that is platinum sensitive.
• PSOC (i.e., epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer) with documented radiographic progression or relapse within 6 to 18 months of most recent platinum-based chemotherapy.
• Female participants of childbearing potential must use effective contraception as defined by study protocol and cannot be pregnant or breastfeeding.
• Histological documentation of incurable, locally advanced, or metastatic non-squamous
• NSCLC that has progressed on prior treatment
• Not more than 2 prior regimens in the metastatic setting, including one prior cytotoxic regimen and one prior non-cytotoxic regimen (prior treatment with adjuvant therapy within 6 months of recurrence is considered a treatment regimen in the metastatic setting).
• For participants with a documented epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement, one additional line of non-cytotoxic prior treatment will be permitted provided the therapy is a targeted agent against the EGFR mutation or ALK rearrangement.
• For participants with lung cancer, centrally confirmed high expression of a sodium-dependent phosphate transporter (NaPi2b) by immunohistochemistry (IHC) is required (i.e., IHC 2+ or 3+).

You may not qualify if:

• Anti-tumor therapy of any kind or major surgery within 4 weeks prior to Day 1.
• For ovarian cancer participants only, platinum-based chemotherapy within 6 months prior to Day 1.
• For ovarian cancer participants only, platinum treatment with more than two platinum-based chemotherapy regiments or more than four anti-cancer regimens, overall, for the treatment of ovarian cancer.
• Palliative radiation within 2 weeks prior to Day 1.
• Toxicity (except alopecia and anorexia) from prior therapy or neuropathy of grades \> 1.
• Evidence of any significant disease or condition that could affect compliance with the protocol or interpretation of results.
• Known active infection (except fungal nail infections).
• History of liver disease or human immunodeficiency virus (HIV).
• Other malignancy within the last 5 years, except for adequately treated or controlled carcinoma in situ of the cervix or skin cancer or primary endometrial cancer of stage \</= 1B.
• Untreated or active central nervous system (CNS) metastases.
• Prior treatment with NaPi2b- targeted therapy.
• Expansion Cohort Only):
• Inadequately controlled hypertension or history of hypertensive crisis or encephalopathy.
• History of heart problems or thrombosis within 6 months prior to study start.
• History of stroke within 6 months prior to study enrollment.

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (4)

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Inst.

Boston, Massachusetts, 02115, United States

Location

The University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

The Sarah Cannon Research Inst

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Interventions

Bevacizumab; Carboplatin; lifastuzumab vedotin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2013
• First Posted: November 26, 2013
• Study Start: December 16, 2013
• Primary Completion: November 9, 2016
• Study Completion: November 9, 2016
• Last Updated: October 4, 2017

Record last verified: 2017-10

Locations

US (4)