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Study to Determine the Safety, Tolerability, Pharmacokinetics and RP2D of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Participants With Locally Advanced or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT03821935
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE January 28, 2019
First Posted Date  ICMJE January 30, 2019
Last Update Posted Date June 9, 2020
Actual Study Start Date  ICMJE February 21, 2019
Estimated Primary Completion Date July 14, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
  • Dose Escalation: Recommended Phase 2 Dose (RP2D) ABBV-151 Monotherapy [ Time Frame: Up to 28 days after the first dose of ABBV-151 monotherapy ]
    The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation portion of the study.
  • Dose Escalation: RP2D ABBV-151 + ABBV-181 Combination Therapy [ Time Frame: Up to 28 days after the first dose of ABBV-151 and ABBV-181 combination therapy ]
    The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study.
  • Dose Expansion: Objective Response Rate (ORR) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
    ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2019)
  • Dose Escalation: Recommended Phase 2 Dose (RP2D) ABB-151 Monotherapy [ Time Frame: Up to 28 days after the first dose of ABBV-151 monotherapy ]
    The ABBV-151 dose level for RP2D may be at or below the maximum tolerated dose (MTD) (or the maximum administered dose [MAD] if the MTD is not identified).The MTD is defined as the highest safe dose administered (where dose limiting toxicities [DLTs] are observed at higher doses) and the MAD is defined as the highest dose of ABBV-151 that is administered as monotherapy. The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation portion of the study.
  • Dose Escalation: RP2D ABB-151 + ABBV-181 Combination Therapy [ Time Frame: Up to 28 days after the first dose of ABBV-151 and ABBV-181 combination therapy ]
    The ABBV-151 dose level for RP2D may be at or below the maximum tolerated dose (MTD) (or the maximum administered dose [MAD] if the MTD is not identified).The MTD is defined as the highest safe dose administered (where dose limiting toxicities [DLTs] are observed at higher doses) and the MAD is defined as the highest dose of ABBV-151 that is administered as monotherapy. The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study.
  • Dose Expansion: Objective Response Rate (ORR) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
    ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
  • Dose Expansion: Duration of Response (DOR) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
    The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.
  • Dose Expansion: Progression-free Survival (PFS) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
    Progression-free survival is defined as the time from the participant's first dose of study treatment (ABBV-151 or ABBV-181) to the first date of either disease progression or death, whichever occurs first.
  • Maximum Observed Serum Concentration (Cmax) [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
    Maximum Serum Concentration (Cmax) of study drug.
  • Time to Maximum Observed Serum Concentration (Tmax) [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
    Time to maximum serum concentration (Tmax) of study drug.
  • Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
    Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ).
  • Terminal-phase Elimination Rate Constant (β) [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
    Apparent terminal phase elimination rate constant (β or Beta).
  • Terminal Phase Elimination Half-life (t1/2) [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
    Terminal phase elimination half-life (t1/2) of study drug.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2019)
  • Dose Expansion: Duration of Response (DOR) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
    The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.
  • Dose Expansion: Progression-free Survival (PFS) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
    Progression-free survival is defined as the time from the participant's first dose of study treatment (ABBV-151 or ABBV-181) to the first date of either disease progression or death, whichever occurs first.
  • Maximum Observed Serum Concentration (Cmax) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
    Maximum Serum Concentration (Cmax) of study drug.
  • Time to Maximum Observed Serum Concentration (Tmax) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
    Time to maximum serum concentration (Tmax) of study drug.
  • Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
    Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ).
  • Terminal-phase Elimination Rate Constant (β) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
    Apparent terminal phase elimination rate constant (β or Beta).
  • Terminal Phase Elimination Half-life (t1/2) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
    Terminal phase elimination half-life (t1/2) of study drug.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Determine the Safety, Tolerability, Pharmacokinetics and RP2D of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Participants With Locally Advanced or Metastatic Solid Tumors
Official Title  ICMJE A Phase 1 First-in Human, Multi-Center, Open Label Dose-Escalation Study to Determine the Safety, Tolerability, Pharmacokinetics and RP2D of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Subjects With Locally Advanced or Metastatic Solid Tumors
Brief Summary The study will determine the recommended Phase 2 dose (RP2D) of ABBV-151 administered as monotherapy and in combination with ABBV-181 as well as to assess the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-151 alone and in combination with ABBV-181. The study will consist of 2 phases: dose escalation and dose expansion.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors Cancer
Intervention  ICMJE
  • Drug: ABBV-151
    liquid for intravenous infusion
  • Drug: ABBV-181
    lyophilized powder for solution for intravenous infusion
Study Arms  ICMJE
  • Experimental: ABBV-151 Monotherapy
    Various doses of ABBV-151 administered during dose escalation, followed by dose expansion of ABBV-151 administered at the Recommended Phase 2 Dose (RP2D).
    Intervention: Drug: ABBV-151
  • Experimental: ABBV-151 + ABBV-181 Combination Therapy
    Various doses of ABBV-151 plus ABBV-181 Dose A administered every 4 weeks (Q4W) during dose escalation, followed by dose expansion of ABBV-151 administered at the RP2D plus ABBV-181 Dose A administered Q4W.
    Interventions:
    • Drug: ABBV-151
    • Drug: ABBV-181
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 28, 2019)
184
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 14, 2022
Estimated Primary Completion Date July 14, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • For Dose Escalation only: Participants with an advanced solid tumor who are considered refractory to or intolerant of all existing therapy(ies) known to provide a clinical benefit for their condition. Additionally, participants who have been offered standard therapies and refused, or who are considered ineligible for standard therapies, may be eligible for this study on a case-by-case basis, after discussion with and agreement from the sponsor. Participants with triple-negative breast cancer (TNBC), pancreatic adenocarcinoma, urothelial cancer, Hepatocellular carcinoma (HCC), or Head and neck squamous cell carcinoma (HNSCC) who are being considered for the dose escalation cohorts must also meet the histology specific eligibility criteria described below for dose expansion
  • For Dose Expansion only participants must meet criteria specific to the type of cancer:
  • TNBC - Female or male participants with confirmed breast adenocarcinoma that is ER-negative, PR-negative, and HER2-negative, (as defined per American Society of Clinical Oncology [ASCO]/College of American Pathology [CAP] guidelines), who must have disease progression during or after at least 1 systemic therapy that included a taxane in the metastatic or recurrent setting.
  • Pancreatic adenocarcinoma and have disease progression during or after 1 systemic therapy (gemcitabine monotherapy or in combination with other agents, FOLFIRINOX [or another regimen including both 5-fluorouracil and oxaliplatin], capecitabine monotherapy or in combination with other agents) administered in the adjuvant, locally advanced, or metastatic setting. If the therapy was used in an adjuvant setting, disease progression must have occurred within 6 months of completing adjuvant therapy.
  • Urothelial cancer of the bladder and urinary tract and must have progressed following treatment with a platinum-based regimen (administered in any line of therapy) and a programmed death 1/programmed death ligand 1 (PD1/PDL1) antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
  • HCC and must have disease progression during or after 1 prior line of systemic therapy.
  • HNSCC (arising from the oral cavity, oropharynx, hypopharynx, or larynx) and must have progressed following treatment with platinum-based regimen (administered in any line of therapy) and a PD1/PDL1 antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
  • Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
  • Participant has adequate bone marrow, renal, hepatic, and coagulation function. Must have a viral status consistent with the requirements described in the protocol specific to type of cancer and stage of study (Dose Escalation or Dose Expansion).

Exclusion Criteria:

  • For Dose Expansion only: Participants (except for participants with urothelial cancer or HNSCC) who have had prior exposure to immunotherapies as listed in the protocol.
  • Has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 5 half-lives or 28 days (whichever is shorter), prior to the first dose of the study drug.
  • Participant has unresolved AEs > Grade 1 from prior anticancer therapy except for alopecia.
  • Has a history of primary immunodeficiency, bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
  • Has a known uncontrolled metastases to the central nervous system (with certain exceptions).
  • Current or prior use of immunosuppressive medication within 14 days prior to the first dose of the study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE Japan,   Australia,   Canada,   France,   Israel,   Korea, Republic of,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03821935
Other Study ID Numbers  ICMJE M19-345
2018-004303-40 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP