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A Study of ABBV-181 in Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03000257
Recruitment Status : Recruiting
First Posted : December 22, 2016
Last Update Posted : October 18, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of ABBV-181. This study will also evaluate the safety and tolerability of ABBV-181 in combination with Rovalpituzumab Tesirine. The study will consist of 2 parts: ABBV-181 monotherapy dose escalation and expansion, and ABBV-181 in combination with Rovalpituzumab Tesirine.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Cancer Drug: Rovalpituzumab Tesirine Drug: ABBV-181 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 182 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-181, a Monoclonal Antibody, as Monotherapy and in Combination With Another Anti-Cancer Therapy in Subjects With Advanced Solid Tumors
Actual Study Start Date : December 14, 2016
Estimated Primary Completion Date : November 25, 2019
Estimated Study Completion Date : November 25, 2019


Arm Intervention/treatment
Experimental: ABBV-181

In the Monotherapy Escalation portion of the study, ABBV-181 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). Based on available safety, pharmacokinetic, and pharmacodynamic data from the dose-escalation part of the study, participants will be enrolled in tumor-specific dose-expansion cohorts to further evaluate ABBV-181 at a dose level which is at or below the Maximum tolerated dose (MTD). In the Monotherapy Expansion portion of the study, ABBV-181 will be administered in 28-day dosing cycles at either 1 dose per cycle or 2 doses per cycle.

In the Combination portion of the study, ABBV-181 will be administered in combination with Rovalpituzumab Tesirine in 21-day dosing cycles. Based on available safety, PK and PD data from the single agent dose-escalation part of the study, a dose for ABBV-181 will be selected to evaluate in combination with Rovalpituzumab Tesirine.

Drug: Rovalpituzumab Tesirine
Intravenous infusion

Drug: ABBV-181
Intravenous infusion

Experimental: ABBV-181 plus Rovalpituzumab Tesirine
Rovalpituzumab Tesirine will be given once every six weeks times two doses and ABBV-181 will be administered every 3 weeks.
Drug: Rovalpituzumab Tesirine
Intravenous infusion

Drug: ABBV-181
Intravenous infusion




Primary Outcome Measures :
  1. Recommended Phase 2 Dose (RPTD) and schedule for ABBV-181 and Rovalpituzumab Tesirine combination [ Time Frame: Up to 6 months ]
    The safety and tolerability of a single dose of ABBV-181 in combination with Rovalpituzumab Tesirine will be assessed in patients with advanced small cell lung cancer (SCLC) to determine the RPTD and schedule for the combination.

  2. Terminal half-life (t1/2) [ Time Frame: Up to 4 weeks after participant's first dose ]
  3. Maximum observed serum concentration (Cmax) [ Time Frame: Up to 12 weeks after participant's first dose ]
  4. Area under the serum concentration time curve (AUC) [ Time Frame: Up to 12 weeks after participant's first dose ]
  5. Number of participants with adverse events [ Time Frame: From first dose of study drug until 90 days following last dose of study drug (up to 24 months) ]
  6. Time to Cmax (Tmax) [ Time Frame: Up to 12 weeks after participant's first dose ]
  7. Recommended Phase 2 Dose (RPTD) for ABBV-181 [ Time Frame: Up to 6 months ]
    If a maximum tolerated dose (MTD) is reached, the RPTD of ABBV-181 will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and other available data.

  8. Maximum tolerated dose (MTD) of ABBV-181 [ Time Frame: Up to 6 months ]
    MTD will be defined at the highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.

  2. Preliminary response and activity of ABBV-181 and Rovalpituzumab Tesirine when given in combination [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    The overall safety and tolerability of ABBV-181 and Rovalpituzumab Tesirine when given in combination will be evaluated. The immunogenicity of the combination will also be evaluated.

  3. Clinical benefit rate (CBR, defined as CR, PR or SD) [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.

  4. Progression-free survival (PFS) [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    PFS time is defined as the time from the participant's first dose of study drug (Day 1) to either the participant's disease progression or death, whichever occurs first.

  5. Duration of objective response (DOR) [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    DOR for a participant is defined as the time from the participant's initial objective response to study drug therapy to disease progression or death, whichever occurs first.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must have an advanced solid tumor and must not be a candidate for surgical resection or other approved therapeutic regimen known to provide clinical benefit. For dose escalation, the participant may have been previously treated with a programmed cell death 1 (PD-I) targeting agent. For dose expansion, the participant must be PD-I/PD-L1 targeting agent naïve. For Combination, the participant must be have SCLC with progressive disease and have failed platinum containing therapy and be PD-1/PD-L1 targeting agent naïve.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for Monotherapy and 0 to 1 for Combination.
  • Participants have adequate bone marrow, renal, hepatic and coagulation function.
  • Participants must have measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the dose escalation portion of the trial. Participants in the expansion cohort must have measurable disease per RECIST version 1.1 or disease evaluable by assessment of tumor antigens.

Exclusion Criteria:

  • Participant has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 5 half-lives, prior to the first dose of ABBV-181 or Rovalpituzumab Tesirine.
  • For Combination therapy, participant must not have had prior exposure to Rovalpituzumab Tesirine or a pyrrolobenzodiazepine (PBD) based drug.
  • Participant has unresolved adverse events greater than grade 1 from prior anticancer therapy except for alopecia.
  • Current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions).
  • History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
  • Confirmed positive test results for human immunodeficiency virus (HIV), or participants with chronic or active hepatitis B or C. Subjects who have a history of hepatitis B or C who have undetectable HBV DNA or HCV RNA are anti-viral therapy may be enrolled.
  • Participant has known history or inflammatory bowel disease, pneumonitis, or known uncontrolled metastases to the central nervous system (CNS) (with certain exceptions).
  • In Japan, participants with a history of or ongoing interstitial lung disease are also excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03000257


Contacts
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

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Sponsors and Collaborators
AbbVie
Investigators
Study Director: AbbVie Inc. AbbVie

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03000257     History of Changes
Other Study ID Numbers: M15-891
2016-002520-89 ( EudraCT Number )
First Posted: December 22, 2016    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:
Cancer
Advanced Solid Tumors
Non-small cell lung cancer (NSCLC)
Triple negative breast cancer
Ovarian cancer
Hepatocellular carcinoma
Gastric cancer
Small cell lung cancer
Mesothelioma
Cholangiocarcinoma
Merkel cell carcinoma
Head and neck cancer