A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Etoposide and Platinum Therapy (PINNACLE)

A Phase 1b/2 Study of OMP-59R5 in Combination With Etoposide and Platinum Therapy in Subjects With Untreated Extensive Stage Small Cell Lung Cancer (PINNACLE)

The study consists of a Phase1b lead-in portion to determine the maximum tolerated dose (MTD) of OMP-59R5 (tarextumab) in combination with etoposide (EP) for 6 cycles followed a Phase 2, multi center, randomized, placebo-controlled portion comparing the efficacy and safety of OMP-59R5 in combination with EP for 6 cycles followed by single agent OMP-59R5 relative to EP alone for 6 cycles in subjects receiving first-line therapy for extensive stage small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Stage IV Small Cell Lung Cancer
• Intervention / Treatment: Drug: OMP-59R5; Drug: Etoposide; Drug: Placebo; Drug: Cisplatin or Carboplatin

Detailed Description

The Phase 1b lead-in portion of the study was conducted to determine the MTD of OMP-59R5 administered along with EP. The Phase 2 portion of the study was multi-center, randomized, and placebo-controlled. Subjects who qualified for enrollment into the Phase 2 portion of the study were randomized in a 1:1 ratio to receive study treatment of tarextumab along with EP (Arm A) or placebo along with EP (Arm B).

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Fort Myers, Florida, United States, 33905
      • Sarah Cannon
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center, PL
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute
    • Atlanta, Georgia, United States, 30341
      • Georgia Cancer Specialists, PC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Univeristy of Chicago Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Greenebaum Cancer Center
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
    • Baltimore, Maryland, United States, 21237
      • Weinberg Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center, Clinical Trials Office
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology , P.A.
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West PC, dba Nebraska Cancer Specialists
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care, Inc.
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center Oncology and Hematology Care Eastside
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Pavilion
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System, Clinical Research Unit, Institute for Translational Oncology Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology-South Austin
    • Bedford, Texas, United States, 76022
      • Texas Oncology-Bedford
    • Dallas, Texas, United States, 75246
      • Texas Oncology, P.A.
    • Houston, Texas, United States, 77030
      • The University of Texas MD A nderson Cancer Center
    • San Antonio, Texas, United States, 78217
      • Cancer Care Network of South Texas
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Oncology and Hematology Associates of Southwest Virginia Inc.
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for the study:

1. Histologically or cytologically documented extensive stage small cell lung cancer.
2. Adults of 18 years of age or older.
3. Performance Status (ECOG) of 0 or 1.
4. Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

5. Adequate organ function:

   1. Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1,500 cells/μL; hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL).
   2. Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault formula).
   3. Adequate hepatic function (alanine aminotransferase [ALT] ≤ 3 x upper limit of normal [ULN], ALT may be ≤ 5 x ULN if due to liver metastases but cannot be associated with concurrent elevated bilirubin >1.5 times the upper limit of normal (ULN) unless it is approved by the Sponsor's Medical Monitor).
   4. Prothrombin Time (PT)/International Normalized Ration (INR) ≤1.5 × ULN, activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
6. Written consent on an Institutional Review Board (IRB)/IndependentEthics Committee (IEC)-approved Informed Consent Form prior to any study-specific evaluation.
7. For women of child-bearing potential, negative serum pregnancy test at screening and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration or the last EP in the study, whichever is discontinued last.
8. Male subjects must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration or the last EP in the study, whichever is discontinued last.

Exclusion Criteria:

Subjects who meet any of the following criteria will not be eligible for participation in the study:

1. Limited stage small cell lung cancer appropriate for radical treatment with chemoradiation.
2. Prior therapy including radiation, chemotherapy or surgery for newly diagnosed extensive stage small cell lung cancer.
3. Presence of any serious or uncontrolled illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled arterial thrombosis, symptomatic pulmonary embolism, and psychiatric illness that would limit compliance with study requirement.
4. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within 6 months prior to the first administration of study drug.

5. A history of malignancy with the exception of:

   1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
   2. Adequately treated stage I cancer from which the subject is currently in remission, or
   3. Any other cancer from which the subject has been disease-free for ≥ 3 years
6. Known human immunodeficiency virus (HIV) infection.
7. Females who are pregnant or breastfeeding.
8. Concurrent use of therapeutic warfarin (prophylactic low dose of warfarin, i.e., 1 mg daily for port catheter is allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OMP-59R5 Combination with Etoposide and Cisplatin	Drug: OMP-59R5; OMP-59R5 administered intravenously; Other Names: Tarextumab; Drug: Etoposide; administered intravenously; Drug: Placebo; administered IV; Drug: Cisplatin or Carboplatin; administered intravenously
Experimental: Etoposide and Cisplatin plus Placebo	Drug: OMP-59R5; OMP-59R5 administered intravenously; Other Names: Tarextumab; Drug: Etoposide; administered intravenously; Drug: Placebo; administered IV; Drug: Cisplatin or Carboplatin; administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: To Determine the Maximum Tolerated Dose (MTD) of OMP-59R5 When Administered With Etoposide and Cisplatin or Carboplatin (Number of Subjects With DLTs)	To determine the MTD of tarextumab when administered on Day 1 of each 21 day cycle along with etoposide 100 mg/m2 on Days 1, 2 and 3, and cisplatin 80 mg/m2 or carboplatin area under the curve (AUC) of 5 mg/mL•min on Day 1 in subjects with untreated extensive stage small cell lung cancer. DLT evaluable population includes all subjects who received at least 1 partial dose of OMP-59R5 during the Phase 1b dose escalation portion of the study including the carboplatin cohort and who had completed Day 21 cycle of 1 OMP-59R5 administration or had discontinued due to drug-related toxicity.	Up to 1 year in absence of unacceptable toxicity or disease progression.
Phase 1b: Overall Response (Response Evaluable Population)	The best overall response is defined as the best Investigator-assessed response recorded from the start of the treatment until disease progression in the following order of importance: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Evaluable (NE). Response evaluable population includes subjects who received 1 partial dose of OMP-59R5 and at at least 1 post tumor assessment.	Up to 1 year in absence of unacceptable toxicity or disease progression.
Phase 2: Progression Free Survival (ITT Population)	To determine the improvement in Progression Free Survival (PFS) resulting from the addition of tarextumab to etoposide and platinum therapy (EP) in subjects receiving first-line therapy for extensive stage small cell lung cancer. PFS is based on the Investigator-assessments of tumor response which is defined as the number of days from randomization until death or disease progression as defined by RECIST criteria for the ITT Population.	Up to 1 year until disease progression or death.
Phase 2: Best Overall Tumor Response Based on Investigator Assessment (ITT Population)	The response rate is the number of subjects per treatment arm who have either a complete response (CR) or partial response (PR) for best overall response (according to RECIST criteria) divided by the number of subjects randomized to the respective arms.	Up to 1 year in absence of unacceptable toxicity or disease progression

Collaborators and Investigators

• Sponsor: OncoMed Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2012
• Primary Completion (Actual): April 18, 2017
• Study Completion (Actual): May 8, 2017

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 20, 2013
• First Posted (Estimate): May 22, 2013

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 7, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Newly diagnosed Stage IV Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Carboplatin; Etoposide; Cisplatin
• Other Study ID Numbers: 59R5-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided