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

NCT ID: NCT03000257

Last Updated: 2022-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 182 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-14
• Study Completion Date: 2022-03-29

Brief Summary

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Tablet taken orally

ABBV-181

Intervention Type: DRUG

Intravenous infusion

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.

Group Type: EXPERIMENTAL

ABBV-181

Intervention Type: DRUG

Intravenous infusion

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.

Group Type: EXPERIMENTAL

Rovalpituzumab Tesirine

Intervention Type: DRUG

Intravenous infusion

ABBV-181

Intervention Type: DRUG

Intravenous infusion

Interventions

Venetoclax

Tablet taken orally

Intervention Type: DRUG

Rovalpituzumab Tesirine

Intravenous infusion

Intervention Type: DRUG

ABBV-181

Intravenous infusion

Intervention Type: DRUG

Other Intervention Names

Budigalimab

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

Moores Cancer Center at UC San Diego /ID# 157374

La Jolla, California, United States

The University of Chicago Medical Center /ID# 157375

Chicago, Illinois, United States

Carolina BioOncology Institute /ID# 157376

Huntersville, North Carolina, United States

South Texas Accelerated Research Therapeutics /ID# 157378

San Antonio, Texas, United States

Virginia Cancer Specialists - Fairfax /ID# 157377

Fairfax, Virginia, United States

Blacktown Hospital /ID# 167386

Blacktown, New South Wales, Australia

St Vincent's Hospital Melbourne /ID# 167552

Fitzroy Melbourne, Victoria, Australia

Linear Clinical Research /ID# 170797

Nedlands, Western Australia, Australia

Medizinische Universitaet Graz /ID# 168752

Graz, Styria, Austria

Universitair Ziekenhuis Antwerpen /ID# 170702

Edegem, Antwerpen, Belgium

UZ Gent /ID# 170881

Ghent, Oost-Vlaanderen, Belgium

Cross Cancer Institute /ID# 167603

Edmonton, Alberta, Canada

Tampere University Hospital /ID# 166839

Tampere, Pirkanmaa, Finland

Docrates Cancer Center /ID# 166838

Helsinki, , Finland

Institut Bergonie /ID# 162662

Bordeaux, Gironde, France

Institut du Cancer de Montpellier - Val d'Aurelle /ID# 163999

Montpellier, Herault, France

Centre Leon Berard /ID# 162660

Lyon, Rhone, France

Institut Gustave Roussy /ID# 162753

Villejuif, Val-de-Marne, France

National Cancer Center Hospital East /ID# 166433

Kashiwa-shi, Chiba, Japan

National Hospital Organization Kyushu Cancer Center /ID# 206229

Fukuoka, Fukuoka, Japan

National Cancer Center Hospital /ID# 166279

Chuo-ku, Tokyo, Japan

Hospital Universitario Fundacion Jimenez Diaz /ID# 163862

Madrid, , Spain

Hospital Universitario HM Sanchinarro /ID# 163861

Madrid, , Spain

Hospital Clinico Universitario de Valencia /ID# 163925

Valencia, , Spain

National Taiwan University Hospital /ID# 163997

Taipei, , Taiwan

Taipei Medical University Hospital /ID# 163998

Taipei, , Taiwan

Countries

United States; Australia; Austria; Belgium; Canada; Finland; France; Japan; Spain; Taiwan

References

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.

Reference Type: DERIVED

PMID: 35034046 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34329846 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34216247 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32770720 (View on PubMed)

Other Identifiers

2016-002520-89

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M15-891

Identifier Type: -

Identifier Source: org_study_id