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

A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-181 as Monotherapy and in Combination With Another Anti-Cancer Therapy in Subjects With Advanced Solid Tumors

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 budigalimab. This study will also evaluate the safety and tolerability of budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax. The study will consist of 3 parts: budigalimab monotherapy dose escalation and expansion, budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Venetoclax; Drug: ABBV-181; Drug: Rovalpituzumab Tesirine

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital /ID# 167386
  • Victoria
    • Fitzroy Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne /ID# 167552
  • Western Australia
    • Nedlands, Western Australia, Australia, 6000
      • Linear Clinical Research /ID# 170797
• Austria
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medizinische Universitaet Graz /ID# 168752
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen /ID# 170702
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 170881
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute /ID# 167603
• Finland
  • Helsinki, Finland, 00180
    • Docrates Cancer Center /ID# 166838
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33520
      • Tampere University Hospital /ID# 166839
• France
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • Institut Bergonie /ID# 162662
  • Herault
    • Montpellier CEDEX 5, Herault, France, 34298
      • Institut du Cancer de Montpellier - Val d'Aurelle /ID# 163999
  • Rhone
    • Lyon CEDEX 08, Rhone, France, 69373
      • Centre Leon Berard /ID# 162660
  • Val-de-Marne
    • Villejuif Cedex, Val-de-Marne, France, 94805
      • Institut Gustave Roussy /ID# 162753
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 166433
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center /ID# 206229
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 166279
• Spain
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz /ID# 163862
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro /ID# 163861
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia /ID# 163925
• Taiwan
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital /ID# 163997
  • Taipei City, Taiwan, 11031
    • Taipei Medical University Hospital /ID# 163998
• United States
  • California
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at UC San Diego /ID# 157374
  • Illinois
    • Chicago, Illinois, United States, 60637-1443
      • The University of Chicago Medical Center /ID# 157375
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute /ID# 157376
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics /ID# 157378
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists - Fairfax /ID# 157377

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Part 2 budigalimab in combination with rovalpituzumab tesirine, the participant must have SCLC with progressive disease and have failed platinum containing therapy and be PD-1/PD-L1 targeting agent naïve. For Part 3 budigalimab in combination with venetoclax, the participant must have locally advanced or metastatic NSCLC and received 1 to 4 prior lines of therapy in the advanced or metastatic setting including 1 regimen that included a PD-1 or PD-L1 targeting agent which was discontinued following disease progression. Participants who are naïve to treatment with a PD-1/PD-L1 targeting agent OR who have received more than 1 regimen containing a PD-1/PD-L1 targeting agent are NOT eligible for Part 3.
• Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for the monotherapy cohort and an ECOG 0 to 1 for budigalimab in combination with rovalpituzumab tesirine cohort (Part 2) and budigalimab in combination with venetoclax (Part 3).
• 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. Participants enrolled in budigalimab in combination with venetoclax cohort (Part 3) must have measurable disease per RECIST version 1.1.

Exclusion Criteria:

• Participant has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, small molecule, herbal therapy, or any investigational therapy within a period of 5 half-lives, prior to the first dose of budigalimab or Rovalpituzumab Tesirine or venetoclax.
• For budigalimab in combination with rovalpituzumab tesirine cohort (Part 2), 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 A, B or C. Participants who have a history of hepatitis B or C who have undetectable hepatitis B (HBV) DNA or hepatitis C (HCV) RNA after 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).
• Participants with a history of or ongoing pneumonitis or interstitial lung disease are also excluded.
• For budigalimab plus venetoclax therapy (Part 3), participant must not receive a strong or moderate inducer or inhibitor of cytochrome P450 (CYP)3A within 7 days before first venetoclax dose.
• For budigalimab plus venetoclax therapy (Part 3), participants with a known gastrointestinal disorder (i.e.: malabsorption syndrome), complication (i.e.: dysphagia) or surgery that could make consumption or absorption of oral medication problematic are also excluded.
• All Cohorts: Participants with a history of Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ABBV-181 plus Venetoclax; Venetoclax will be taken once daily beginning 7 days prior to cycle 1 and continuing daily for a 28 day cycle and ABBV-181 will be administered every 4 weeks.	Drug: Venetoclax; Tablet taken orally; Drug: ABBV-181; Intravenous infusion; Other Names: Budigalimab
EXPERIMENTAL: ABBV-181; 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 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. 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 or venetoclax.	Drug: ABBV-181; Intravenous infusion; Other Names: Budigalimab
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: ABBV-181; Intravenous infusion; Other Names: Budigalimab; Drug: Rovalpituzumab Tesirine; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab	If a maximum tolerated dose (MTD) is reached, the RPTD of budigalimab 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.	Up to 6 months
Part 1: Maximum tolerated dose (MTD) of Budigalimab	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.	Up to 6 months
Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab	Terminal phase elimination half-life (t1/2) of Budigalimab	Up to 4 Weeks
Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab	Maximum Serum Concentration (Cmax) of Budigalimab	Up to 12 Weeks
Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab	Time to maximum plasma concentration of Budigalimab	Up to 12 Weeks
Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab	Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab	Up to 12 Weeks
Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination	The safety and tolerability of a single dose of Budigalimab 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.	Up to 6 Months
Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination.	The safety and tolerability of Budigalimab in combination with venetoclax will be assessed in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) to determine the RPTD for the combination.	Up to 6 Months
Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax	Maximum Serum Concentration (Cmax) for Venetoclax	Up to 12 Weeks
Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax	Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24)) of Venetoclax	Up to 12 Weeks
Part 3: Time to Cmax (Tmax) of Venetoclax	Time to maximum plasma concentration of of Venetoclax	Up to 12 Weeks
Part 1, Part 2, Part 3: Number of Participants with Adverse Events	An adverse event 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.	From first dose of study drug until 90 days following last dose of study drug (up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Terminal Half-life (t1/2) of Budigalimab	Terminal phase elimination half-life (t1/2) of Budigalimab	Up to 4 Weeks
Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine	Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine	Up to 4 Weeks
Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine	Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine	Up to 12 Weeks
Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine	Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Rovalpituzumab Tesirine	Up to 12 Weeks
Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab	Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab	Up to 12 Weeks
Part 2: Time to Cmax (Tmax) of Budigalimab	Time to maximum plasma concentration of Budigalimab	Up to 12 Weeks
Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine	Time to maximum plasma concentration of Rovalpituzumab Tesirine	Up to 12 Weeks
Part 1 and Part 3: Objective response rate (ORR)	ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.	First dose of study drug through at least 30 days after last dose of study drug.
Part 1 and Part 3: Clinical benefit rate (CBR, defined as CR, PR or SD)	CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.	First dose of study drug through at least 30 days after last dose of study drug.
Part 1 and Part 3: Progression-free survival (PFS)	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.	First dose of study drug through at least 30 days after last dose of study drug.
Part 1, Part 2 and Part 3: Duration of objective response (DOR)	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.	First dose of study drug through at least 30 days after last dose of study drug.

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Lambert SL, Zhang C, Guo C, Turan T, Masica DL, Englert S, Fang Y, Sheridan J, McLaughlin RT, Tribouley C, Vosganian G, Afar D. Association of Baseline and Pharmacodynamic Biomarkers With Outcomes in Patients Treated With the PD-1 Inhibitor Budigalimab. J Immunother. 2022 Apr 1;45(3):167-179. doi: 10.1097/CJI.0000000000000408.
• Calvo E, Spira A, Miguel M, Kondo S, Gazzah A, Millward M, Prenen H, Rottey S, Warburton L, Alanko T, Cassier PA, Yoh K, Italiano A, Moreno V, Peltola K, Seto T, Toyozawa R, Afar DE, Englert S, Komarnitsky P, Lambert S, Parikh A, Vosganian G, Gao B. Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Cancer Treat Res Commun. 2021;28:100405. doi: 10.1016/j.ctarc.2021.100405. Epub 2021 May 25.
• Italiano A, Cassier PA, Lin CC, Alanko T, Peltola KJ, Gazzah A, Shiah HS, Calvo E, Cervantes A, Roda D, Tosi D, Gao B, Millward M, Warburton L, Tanner M, Englert S, Lambert S, Parikh A, Afar DE, Vosganian G, Moreno V. First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma. Cancer Immunol Immunother. 2022 Feb;71(2):417-431. doi: 10.1007/s00262-021-02973-w. Epub 2021 Jul 3.
• Powderly J, Spira A, Kondo S, Doi T, Luke JJ, Rasco D, Gao B, Tanner M, Cassier PA, Gazzah A, Italiano A, Tosi D, Afar DE, Parikh A, Engelhardt B, Englert S, Lambert SL, Kasichayanula S, Mensing S, Menon R, Vosganian G, Tolcher A. Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181). Clin Transl Sci. 2021 Jan;14(1):277-287. doi: 10.1111/cts.12855. Epub 2020 Dec 26.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 14, 2016
• Primary Completion (ACTUAL): March 29, 2022
• Study Completion (ACTUAL): March 29, 2022

Study Registration Dates

• First Submitted: December 15, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (ESTIMATE): December 22, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 13, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Cancer; Gastric cancer; Ovarian cancer; Advanced Solid Tumors; Non-small cell lung cancer (NSCLC); Hepatocellular carcinoma; Cholangiocarcinoma; Head and neck cancer; Small cell lung cancer; Mesothelioma; Triple negative breast cancer; Budigalimab; Merkel cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: M15-891; 2016-002520-89 (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