A Study of ABBV-927 and ABBV-181, an Immunotherapy, in Participants With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT02988960
• Recruitment Status: Active, not recruiting
• First Posted: December 12, 2016
• Last Update Posted: February 14, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: December 8, 2016
• First Posted Date: December 12, 2016
• Last Update Posted Date: February 14, 2023
• Actual Study Start Date: February 22, 2017
• Estimated Primary Completion Date: February 10, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 16, 2020)

• Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 [ Time Frame: Up to 8 weeks ]
  The MTD and the RPTD of ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 will be determined during the dose escalation phase of the study. Once the RPTD has been determined, the dose expansion portion will begin.
• Time to Cmax (Tmax) of ABBV-927 [ Time Frame: Up to 12 weeks after participant's first dose ]
  Time to Cmax (Tmax) of ABBV-927.
• Maximum observed serum concentration (Cmax) of ABBV-927 [ Time Frame: Up to 12 weeks after participant's first dose ]
  Maximum observed serum concentration (Cmax) of ABBV-927.
• Terminal-Phase Elimination Rate Constant (β) of ABBV-927 [ Time Frame: Up to 12 weeks after participant's first dose ]
  Terminal-phase elimination rate constant (β)of ABBV-927.
• Terminal half-life (t1/2) of ABBV-927 [ Time Frame: Up to 4 weeks after participant's first dose ]
  Terminal half-life (t1/2) of ABBV-927.
• Area under the serum concentration-time curve (AUCt) of ABBV-927 [ Time Frame: Up to 12 weeks after participant's first dose ]
  Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-927.
• Time to Cmax (Tmax) of ABBV-181 [ Time Frame: Up to 12 weeks after participant's first dose ]
  Time to Cmax (Tmax) of ABBV-181.
• Maximum observed serum concentration (Cmax) of ABBV-181 [ Time Frame: Up to 12 weeks after participant's first dose ]
  Maximum observed serum concentration (Cmax) of ABBV-181.
• Terminal-Phase Elimination Rate Constant (β) of ABBV-181 [ Time Frame: Up to 12 weeks after participant's first dose ]
  Terminal-phase elimination rate constant (β)of ABBV-181.
• Terminal half-life (t1/2) of ABBV-181 [ Time Frame: Up to 4 weeks after participant's first dose ]
  Terminal half-life (t1/2) of ABBV-181.
• Area under the serum concentration-time curve (AUCt) of ABBV-181 [ Time Frame: Up to 12 weeks after participant's first dose ]
  Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-181.
• Number of Participants with Adverse Events [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Original Primary Outcome Measures (submitted: December 9, 2016)

• Number of participants with adverse events [ Time Frame: First dose of study drug through at least 100 days after end of treatment or until the start of another anticancer therapy; up to 2 years after last participants first dose ]
• Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with nivolumab [ Time Frame: Up to 8 weeks ]
  The MTD and the RPTD of ABBV-927 when administered as monotherapy or as combination therapy with nivolumab will be determined during the dose escalation phase of the study. Once the RPTD has been determined, the dose expansion portion will begin.
• Maximum observed serum concentration (Cmax) of ABBV-927 [ Time Frame: Up to 12 weeks after participant's first dose ]
• Time to Cmax (Tmax) of ABBV-927 [ Time Frame: Up to 12 weeks after participant's first dose ]
• Area under the serum concentration-time curve (AUC) of ABBV-927 [ Time Frame: Up to 12 weeks after participant's first dose ]
• Terminal half-life (t1/2) of ABBV-927 [ Time Frame: Up to 4 weeks after participant's first dose ]

Current Secondary Outcome Measures (submitted: September 16, 2020)

• Clinical benefit rate (CBR, defined as the percentage of participants with a confirmed partial, complete response, or stable disease for at least 24 weeks to the treatment) [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease for at least 24 weeks to the treatment.
• Duration of objective response (DOR) [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first.
• Objective response rate (ORR) [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  ORR is defined as the proportion of participants with a confirmed partial or complete response to the treatment.
• Progression-free survival (PFS) [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  PFS time is defined as the time from the first dose of ABBV-927 to disease progression or death, whichever occurs first.

Original Secondary Outcome Measures (submitted: December 9, 2016)

• Objective response rate (ORR) [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  ORR is defined as the proportion of participants with a confirmed partial or complete response to the treatment
• Duration of objective response (DOR) [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first.
• Clinical benefit rate (CBR, defined as the percentage of participants with a confirmed partial, complete response, or stable disease for at least 24 weeks to the treatment) [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease for at least 24 weeks to the treatment.
• Progression-free survival (PFS) [ Time Frame: Up to 30 days after and up to 24-month of treatment period ]
  PFS time is defined as the time from the first dose of ABBV-927 to disease progression or death, whichever occurs first.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of ABBV-927 and ABBV-181, an Immunotherapy, in Participants With Advanced Solid Tumors
• Official Title: A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-927 and ABBV-181, an Immunotherapy, in Subjects With Advanced Solid Tumors
• Brief Summary: This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of ABBV-927, and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 in participants with advanced solid tumors.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumors Cancer

Intervention

• Drug: ABBV-927
  Intravenous
• Drug: ABBV-927
  Intratumoral
• Drug: ABBV-181
  Intravenous
  Other Name: Budigalimab

Study Arms

• Experimental: Escalating Arm 1: ABBV-927
  Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927.
  Intervention: Drug: ABBV-927
• Experimental: Escalating Arm 2: ABBV-927
  Participants with solid tumors will receive escalating intratumoral (IT) doses of ABBV-927.
  Intervention: Drug: ABBV-927
• Experimental: Escalating Arm 3: ABBV-927+ABBV-181
  Participants with Non-Small Cell Lung Cancer (NSCLC) will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181.
  Interventions:

  • Drug: ABBV-927
  • Drug: ABBV-181
• Experimental: Escalating Arm 4: ABBV-927+ABBV-181
  Participants with Head and Neck Squamous Cell Carcinoma (HNSCC) will receive escalating IT doses of ABBV-927 and IV doses of ABBV-181.
  Interventions:

  • Drug: ABBV-927
  • Drug: ABBV-181
• Experimental: Escalating Arm 5 (Japan): ABBV-927
  Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927.
  Intervention: Drug: ABBV-927
• Experimental: Escalating Arm 6 (Japan): ABBV-927+ABBV-181
  Participants with solid tumors will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181.
  Interventions:

  • Drug: ABBV-927
  • Drug: ABBV-181
• Experimental: Expansion Arm A: ABBV-927
  Additional participants with HNSCC or NSCLC will receive intravenous (IV) doses of ABBV-927.
  Intervention: Drug: ABBV-927
• Experimental: Expansion Arm B: ABBV-927+ABBV-181
  Additional participants with HNSCC will receive IT doses of ABBV-927 and IV doses of ABBV-181.
  Interventions:

  • Drug: ABBV-927
  • Drug: ABBV-181
• Experimental: Expansion Arm C: ABBV-927+ABBV-181
  Additional participants with NSCLC will receive IV doses of ABBV-927 and IV doses of ABBV-181.
  Interventions:

  • Drug: ABBV-927
  • Drug: ABBV-181

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 25, 2022): 163
• Original Estimated Enrollment (submitted: December 9, 2016): 180
• Estimated Study Completion Date: February 10, 2024
• Estimated Primary Completion Date: February 10, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
• Participants have adequate bone marrow, kidney and liver function.
• Participants with a history of chronic heart failure or significant cardiovascular disease must have an echocardiogram or multigated acquisition scan indicating left ventricular ejection fraction greater than or equal to 45% within 28 days prior to the first dose of study drug.
• Participants must have creatinine clearance greater than or equal to 50 mL/min as measured by 24-hour urine or estimated by the Cockcroft-Gault formula.
• Participants must have total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase and alanine aminotransferase less than or equal to 2.5 times ULN.
• Participants in all monotherapy arms must have an advanced solid tumor that has progressed on standard therapies known to provide clinical benefit or the participants are intolerant to such therapies.
• Participants in all combination therapy arms must have recurrent or metastatic HNSCC or NSCLC and previously received platinum-based therapy and progressed either during or after anti-programmed death ligand 1 (PDL1)-based therapy. In addition, participants must have received only one prior immunotherapy.
• The Sponsor may decide to limit the specific tumor types selected or treatment settings for specific arms based on evidence gathered.

Exclusion Criteria:

• Participant must not have an active or prior documented autoimmune disease in the last 2 years.
• Participant must not have current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions).
• Participant must not have a history of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, previous clinical diagnosis of tuberculosis, inflammatory bowel disease, interstitial lung disease, or immune-mediated pneumonitis.
• Participant must not have a history of clinically significant uncontrolled condition(s) including but not limited to the following: uncontrolled hypertension; symptomatic congestive heart failure; unstable angina pectoris or cardiac arrhythmia including atrial fibrillation.
• Participant must not have a history of coagulopathy or a platelet disorder associated with significant clinical risk of thromboembolic event in the judgement of the investigator, or major thromboembolic event within 6 months prior to the first dose of study treatment.
• Participant must not have a prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis while receiving immunotherapy.
• Participant must not have a known uncontrolled malignancy of the central nervous system.
• Participants in all combination therapy arms must not have a history of exposure to an immunotherapy experiencing an immune-mediated adverse event that required permanent discontinuation of the immunotherapy.
• Female participants must not be pregnant, breastfeeding or considering becoming pregnant during the study or for at least 3 or 5 months (for monotherapy and combination therapy participants, respectively) after the last dose of study drug.
• Male participants must not be considering fathering a child or donating sperm during the study or for at least 3 or 5 months (for monotherapy and combination therapy participants, respectively) after the last dose of study drug.
• Participant is judged by the investigator to have evidence of hemolysis.
• For Japan only, participants with a history of interstitial lung disease (pneumonitis) or current interstitial lung disease (pneumonitis).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, France, Japan, Korea, Republic of, Spain, United States

Administrative Information

• NCT Number: NCT02988960
• Other Study ID Numbers: M15-862; 2016-002219-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

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.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: February 2023