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

NCT03000257 | Completed Phase 1 FDA Drug

• 2 other identifiers: M15-8912016-002520-89
• Study Type: interventional
• Target: 182
• Locations: 9 countries
• Sites: 23

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

Keywords

Budigalimab; Cancer; Advanced Solid Tumors; Non-small cell lung cancer (NSCLC); Triple negative breast cancer; Ovarian cancer; Hepatocellular carcinoma; Gastric cancer; Small cell lung cancer; Mesothelioma; Cholangiocarcinoma; Merkel cell carcinoma; Head and neck cancer

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (11)

• Part 2: Terminal Half-life (t1/2) of Budigalimab

  Up to 4 Weeks

• Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine

  Up to 4 Weeks

• Part 2: Maximum Observed 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

  Up to 12 Weeks

• Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab

  Up to 12 Weeks

Study Arms (3)

ABBV-181 plus Venetoclax

EXPERIMENTAL

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; Drug: ABBV-181

ABBV-181

EXPERIMENTAL

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

ABBV-181 plus Rovalpituzumab Tesirine

EXPERIMENTAL

Rovalpituzumab Tesirine will be given once every six weeks times two doses and ABBV-181 will be administered every 3 weeks.

Drug: Rovalpituzumab Tesirine; Drug: ABBV-181

Interventions

Venetoclax DRUG

Tablet taken orally

ABBV-181 plus Venetoclax

Rovalpituzumab Tesirine DRUG

Intravenous infusion

ABBV-181 plus Rovalpituzumab Tesirine

ABBV-181 DRUG

Intravenous infusion

Also known as: Budigalimab

ABBV-181; ABBV-181 plus Rovalpituzumab Tesirine; ABBV-181 plus Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• AbbVie: lead

Study Sites (26)

Moores Cancer Center at UC San Diego /ID# 157374

La Jolla, California, 92093, United States

Location

The University of Chicago Medical Center /ID# 157375

Chicago, Illinois, 60637-1443, United States

Location

Carolina BioOncology Institute /ID# 157376

Huntersville, North Carolina, 28078, United States

Location

South Texas Accelerated Research Therapeutics /ID# 157378

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists - Fairfax /ID# 157377

Fairfax, Virginia, 22031, United States

Location

Blacktown Hospital /ID# 167386

Blacktown, New South Wales, 2148, Australia

Location

St Vincent's Hospital Melbourne /ID# 167552

Fitzroy Melbourne, Victoria, 3065, Australia

Location

Linear Clinical Research /ID# 170797

Nedlands, Western Australia, 6000, Australia

Location

Medizinische Universitaet Graz /ID# 168752

Graz, Styria, 8036, Austria

Location

Universitair Ziekenhuis Antwerpen /ID# 170702

Edegem, Antwerpen, 2650, Belgium

Location

UZ Gent /ID# 170881

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Cross Cancer Institute /ID# 167603

Edmonton, Alberta, T6G 1Z2, Canada

Location

Tampere University Hospital /ID# 166839

Tampere, Pirkanmaa, 33520, Finland

Location

Docrates Cancer Center /ID# 166838

Helsinki, 00180, Finland

Location

Institut Bergonie /ID# 162662

Bordeaux, Gironde, 33000, France

Location

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

Montpellier, Herault, 34298, France

Location

Centre Leon Berard /ID# 162660

Lyon, Rhone, 69373, France

Location

Institut Gustave Roussy /ID# 162753

Villejuif, Val-de-Marne, 94805, France

Location

National Cancer Center Hospital East /ID# 166433

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Hospital Organization Kyushu Cancer Center /ID# 206229

Fukuoka, Fukuoka, 811-1395, Japan

Location

National Cancer Center Hospital /ID# 166279

Chuo-ku, Tokyo, 104-0045, Japan

Location

Hospital Universitario Fundacion Jimenez Diaz /ID# 163862

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro /ID# 163861

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia /ID# 163925

Valencia, 46010, Spain

Location

National Taiwan University Hospital /ID# 163997

Taipei, 100, Taiwan

Location

Taipei Medical University Hospital /ID# 163998

Taipei, 11031, Taiwan

Location

Related Publications (4)

• 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.

  PMID: 35034046 DERIVED

• 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.

  PMID: 34329846 DERIVED

• 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.

  PMID: 34216247 DERIVED

• 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.

  PMID: 32770720 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Hepatocellular; Stomach Neoplasms; Small Cell Lung Carcinoma; Mesothelioma; Cholangiocarcinoma; Carcinoma, Merkel Cell; Head and Neck Neoplasms

Interventions

venetoclax; rovalpituzumab tesirine; budigalimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Adenoma; Neoplasms, Mesothelial; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: December 22, 2016
• Study Start: December 14, 2016
• Primary Completion: March 29, 2022
• Study Completion: March 29, 2022
• Last Updated: April 14, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); ES (3); CA (1); US (5); TW (2); FR (4); FI (2); JP (3); BE (2)