Clinical trial NCT03000257: A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-12-22
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab
timeFrame: Up to 6 months
measure: Part 1: Maximum tolerated dose (MTD) of Budigalimab
timeFrame: Up to 6 months
measure: Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab
timeFrame: Up to 4 Weeks
measure: Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab
timeFrame: Up to 12 Weeks
measure: Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab
timeFrame: Up to 12 Weeks
measure: Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab
timeFrame: Up to 12 Weeks
measure: Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination
timeFrame: Up to 6 Months
measure: Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination.
timeFrame: Up to 6 Months
measure: Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax
timeFrame: Up to 12 Weeks
measure: Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax
timeFrame: Up to 12 Weeks
measure: Part 3: Time to Cmax (Tmax) of Venetoclax
timeFrame: Up to 12 Weeks
measure: Part 1, Part 2, Part 3: Number of Participants with Adverse Events
timeFrame: From first dose of study drug until 90 days following last dose of study drug (up to 24 months)
Secondary outcomes:
measure: Part 2: Terminal Half-life (t1/2) of Budigalimab
timeFrame: Up to 4 Weeks
measure: Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine
timeFrame: Up to 4 Weeks
measure: Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine
timeFrame: Up to 12 Weeks
measure: Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine
timeFrame: Up to 12 Weeks
measure: Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab
timeFrame: Up to 12 Weeks
measure: Part 2: Time to Cmax (Tmax) of Budigalimab
timeFrame: Up to 12 Weeks
measure: Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine
timeFrame: Up to 12 Weeks
measure: Part 1 and Part 3: Objective response rate (ORR)
timeFrame: First dose of study drug through at least 30 days after last dose of study drug.
measure: Part 1 and Part 3: Clinical benefit rate (CBR, defined as CR, PR or SD)
timeFrame: First dose of study drug through at least 30 days after last dose of study drug.
measure: Part 1 and Part 3: Progression-free survival (PFS)
timeFrame: First dose of study drug through at least 30 days after last dose of study drug.
measure: Part 1, Part 2 and Part 3: Duration of objective response (DOR)
timeFrame: First dose of study drug through at least 30 days after last dose of study drug.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Center at UC San Diego /ID# 157374
state: California
city: Chicago
country: United States
facility: The University of Chicago Medical Center /ID# 157375
state: Illinois
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 157376
state: North Carolina
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics /ID# 157378
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax /ID# 157377
state: Virginia
city: Blacktown
country: Australia
facility: Blacktown Hospital /ID# 167386
state: New South Wales
city: Fitzroy Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne /ID# 167552
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research /ID# 170797
state: Western Australia
city: Graz
country: Austria
facility: Medizinische Universitaet Graz /ID# 168752
state: Steiermark
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen /ID# 170702
state: Antwerpen
city: Gent
country: Belgium
facility: UZ Gent /ID# 170881
state: Oost-Vlaanderen
city: Edmonton
country: Canada
facility: Cross Cancer Institute /ID# 167603
state: Alberta
city: Tampere
country: Finland
facility: Tampere University Hospital /ID# 166839
state: Pirkanmaa
city: Helsinki
country: Finland
facility: Docrates Cancer Center /ID# 166838
city: Bordeaux
country: France
facility: Institut Bergonie /ID# 162662
state: Gironde
city: Montpellier CEDEX 5
country: France
facility: Institut du Cancer de Montpellier - Val d'Aurelle /ID# 163999
state: Herault
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 162660
state: Rhone
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 162753
state: Val-de-Marne
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 166433
state: Chiba
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Kyushu Cancer Center /ID# 206229
state: Fukuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 166279
state: Tokyo
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 163862
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 163861
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 163925
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 163997
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital /ID# 163998
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.