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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 Subjects With Locally Advanced or Metastatic Solid Tumors

NCT03821935

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: M19-345
  • NCT ID: NCT03821935

Conditions

  • Advanced Solid Tumors Cancer

Interventions

DrugSynonymsArms
ABBV-151ABBV-151 Monotherapy
ABBV-181ABBV-151 + ABBV-181 Combination Therapy

Purpose

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. In the Dose Escalation phase, the ABBV-151 monotherapy arm will be initiated first and the combination therapy of ABBV-151 plus ABBV-181 will begin once the first 2 or more dose levels of ABBV-151 monotherapy have been declared safe. During the Dose Expansion phase of the study, ABBV-151 monotherapy or in combination with ABBV-181 will be at the RP2D determined during the Dose Escalation phase.

Trial Arms

NameTypeDescriptionInterventions
ABBV-151 MonotherapyExperimentalVarious doses of ABBV-151 administered by intravenous (IV) infusion.
  • ABBV-151
ABBV-151 + ABBV-181 Combination TherapyExperimentalABBV-151 administered by IV infusion at the recommended phase two dose (RPTD) from the dose escalation stage of this study plus ABBV-181 500 mg administered by IV infusion every 4 weeks (Q4W).
  • ABBV-151
  • ABBV-181

Eligibility Criteria

        Inclusion Criteria:

          -  For Dose Escalation only: Subjects 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, subjects 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. Subjects 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 subjects must meet criteria specific to the type of cancer:

          -  TNBC and must have disease progression during or after at least 1 systemic therapy 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).

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

          -  Subject 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: All subjects, except for subjects with urothelial cancer or
             HNSCC, must not 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.

          -  Subject has no 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation: Recommended Phase 2 Dose (RP2D) ABB-151 Monotherapy
Time Frame:Up to 28 days after the first dose of ABBV-151 monotherapy
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Dose Expansion: Duration of Response (DOR)
Time Frame:Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Safety Issue:
Description: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.
Measure:Dose Expansion: Progression-free Survival (PFS)
Time Frame:Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Safety Issue:
Description: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.
Measure:Maximum Observed Serum Concentration (Cmax)
Time Frame:Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14)
Safety Issue:
Description:Maximum Serum Concentration (Cmax) of study drug.
Measure:Time to Maximum Observed Serum Concentration (Tmax)
Time Frame:Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14)
Safety Issue:
Description:Time to maximum serum concentration (Tmax) of study drug.
Measure: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)
Safety Issue:
Description:Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ).
Measure:Terminal-phase Elimination Rate Constant (β)
Time Frame:Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14)
Safety Issue:
Description:Apparent terminal phase elimination rate constant (β or Beta).
Measure:Terminal Phase Elimination Half-life (t1/2)
Time Frame:Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14)
Safety Issue:
Description:Terminal phase elimination half-life (t1/2) of study drug.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Advanced Solid Tumors Cancer
  • cancer
  • Solid Tumors
  • metastatic
  • monotherapy
  • combination therapy
  • triple negative breast cancer (TNBC)
  • pancreatic adenocarcinoma
  • urothelial cancer, hepatocellular carcinoma (HCC), head and neck squamous cell carcinoma (HNSCC)

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