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

A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-927 and ABBV-181, an Immunotherapy, in Subjects With Advanced Solid Tumors

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumors Cancer
• Intervention / Treatment: Drug: ABBV-181; Drug: ABBV-927; Drug: ABBV-927

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula Oncology Centre /ID# 164372
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health /ID# 171189
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre /ID# 200819
• France
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • Institut Bergonie /ID# 162665
  • Herault
    • Montpellier CEDEX 5, Herault, France, 34298
      • Duplicate_Institut Regional du Cancer /ID# 163609
  • Rhone
    • Lyon CEDEX 08, Rhone, France, 69373
      • Centre Leon Berard /ID# 162663
  • Val-de-Marne
    • Villejuif Cedex, Val-de-Marne, France, 94805
      • Institut Gustave Roussy /ID# 162666
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 216870
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 217758
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital /ID# 166291
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Yonsei University Health System Severance Hospital /ID# 166292
• Spain
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz /ID# 200128
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro /ID# 200127
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe /ID# 200975
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro, Majadahonda /ID# 200129
• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Researc /ID# 156324
  • Illinois
    • Chicago, Illinois, United States, 60637-1443
      • The University of Chicago Medical Center /ID# 155264
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital /ID# 155267
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute /ID# 155265
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1632
      • Tennessee Oncology-Nashville Centennial /ID# 158654
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center /ID# 155263
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists - Fairfax /ID# 155266

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escalating Arm 1: ABBV-927; Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927.	Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral
Experimental: Escalating Arm 2: ABBV-927; Participants with solid tumors will receive escalating intratumoral (IT) doses of ABBV-927.	Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral
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.	Drug: ABBV-181; Intravenous; Other Names: Budigalimab; Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral
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.	Drug: ABBV-181; Intravenous; Other Names: Budigalimab; Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral
Experimental: Escalating Arm 5 (Japan): ABBV-927; Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927.	Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral
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.	Drug: ABBV-181; Intravenous; Other Names: Budigalimab; Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral
Experimental: Expansion Arm A: ABBV-927; Additional participants with HNSCC or NSCLC will receive intravenous (IV) doses of ABBV-927.	Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral
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.	Drug: ABBV-181; Intravenous; Other Names: Budigalimab; Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral
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.	Drug: ABBV-181; Intravenous; Other Names: Budigalimab; Drug: ABBV-927; Intravenous; Drug: ABBV-927; Intratumoral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181	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.	Up to 8 weeks
Time to Cmax (Tmax) of ABBV-927	Time to Cmax (Tmax) of ABBV-927.	Up to 12 weeks after participant's first dose
Maximum observed serum concentration (Cmax) of ABBV-927	Maximum observed serum concentration (Cmax) of ABBV-927.	Up to 12 weeks after participant's first dose
Terminal-Phase Elimination Rate Constant (β) of ABBV-927	Terminal-phase elimination rate constant (β)of ABBV-927.	Up to 12 weeks after participant's first dose
Terminal half-life (t1/2) of ABBV-927	Terminal half-life (t1/2) of ABBV-927.	Up to 4 weeks after participant's first dose
Area under the serum concentration-time curve (AUCt) of ABBV-927	Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-927.	Up to 12 weeks after participant's first dose
Time to Cmax (Tmax) of ABBV-181	Time to Cmax (Tmax) of ABBV-181.	Up to 12 weeks after participant's first dose
Maximum observed serum concentration (Cmax) of ABBV-181	Maximum observed serum concentration (Cmax) of ABBV-181.	Up to 12 weeks after participant's first dose
Terminal-Phase Elimination Rate Constant (β) of ABBV-181	Terminal-phase elimination rate constant (β)of ABBV-181.	Up to 12 weeks after participant's first dose
Terminal half-life (t1/2) of ABBV-181	Terminal half-life (t1/2) of ABBV-181.	Up to 4 weeks after participant's first dose
Area under the serum concentration-time curve (AUCt) of ABBV-181	Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-181.	Up to 12 weeks after participant's first dose
Number of Participants with Adverse Events	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.	Up to 30 days after and up to 24-month of treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Up to 30 days after and up to 24-month of treatment period
Duration of objective response (DOR)	DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first.	Up to 30 days after and up to 24-month of treatment period
Objective response rate (ORR)	ORR is defined as the proportion of participants with a confirmed partial or complete response to the treatment.	Up to 30 days after and up to 24-month of treatment period
Progression-free survival (PFS)	PFS time is defined as the time from the first dose of ABBV-927 to disease progression or death, whichever occurs first.	Up to 30 days after and up to 24-month of treatment period

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2017
• Primary Completion (Estimated): March 29, 2024
• Study Completion (Estimated): March 29, 2024

Study Registration Dates

• First Submitted: December 8, 2016
• First Submitted That Met QC Criteria: December 9, 2016
• First Posted (Estimated): December 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Non-small cell lung cancer (NSCLC); Pancreatic adenocarcinoma; Advanced solid tumor; ABBV-181; Budigalimab; ABBV-927; Cutaneous melanoma; Squamous cell carcinoma of the head and neck (SCCHN)
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: M15-862; 2016-002219-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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