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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03000257




Registration number
NCT03000257
Ethics application status
Date submitted
15/12/2016
Date registered
22/12/2016
Date last updated
14/04/2022

Titles & IDs
Public title
A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
2016-002520-89
Secondary ID [2] 0 0
M15-891
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Rovalpituzumab Tesirine
Treatment: Drugs - ABBV-181

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.

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.

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.


Treatment: Drugs: Venetoclax
Tablet taken orally

Treatment: Drugs: Rovalpituzumab Tesirine
Intravenous infusion

Treatment: Drugs: ABBV-181
Intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab
Timepoint [1] 0 0
Up to 6 months
Primary outcome [2] 0 0
Part 1: Maximum tolerated dose (MTD) of Budigalimab
Timepoint [2] 0 0
Up to 6 months
Primary outcome [3] 0 0
Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab
Timepoint [3] 0 0
Up to 4 Weeks
Primary outcome [4] 0 0
Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab
Timepoint [4] 0 0
Up to 12 Weeks
Primary outcome [5] 0 0
Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab
Timepoint [5] 0 0
Up to 12 Weeks
Primary outcome [6] 0 0
Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab
Timepoint [6] 0 0
Up to 12 Weeks
Primary outcome [7] 0 0
Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination
Timepoint [7] 0 0
Up to 6 Months
Primary outcome [8] 0 0
Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination.
Timepoint [8] 0 0
Up to 6 Months
Primary outcome [9] 0 0
Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax
Timepoint [9] 0 0
Up to 12 Weeks
Primary outcome [10] 0 0
Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax
Timepoint [10] 0 0
Up to 12 Weeks
Primary outcome [11] 0 0
Part 3: Time to Cmax (Tmax) of Venetoclax
Timepoint [11] 0 0
Up to 12 Weeks
Primary outcome [12] 0 0
Part 1, Part 2, Part 3: Number of Participants with Adverse Events
Timepoint [12] 0 0
From first dose of study drug until 90 days following last dose of study drug (up to 24 months)
Secondary outcome [1] 0 0
Part 2: Terminal Half-life (t1/2) of Budigalimab
Timepoint [1] 0 0
Up to 4 Weeks
Secondary outcome [2] 0 0
Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine
Timepoint [2] 0 0
Up to 4 Weeks
Secondary outcome [3] 0 0
Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine
Timepoint [3] 0 0
Up to 12 Weeks
Secondary outcome [4] 0 0
Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine
Timepoint [4] 0 0
Up to 12 Weeks
Secondary outcome [5] 0 0
Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab
Timepoint [5] 0 0
Up to 12 Weeks
Secondary outcome [6] 0 0
Part 2: Time to Cmax (Tmax) of Budigalimab
Timepoint [6] 0 0
Up to 12 Weeks
Secondary outcome [7] 0 0
Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine
Timepoint [7] 0 0
Up to 12 Weeks
Secondary outcome [8] 0 0
Part 1 and Part 3: Objective response rate (ORR)
Timepoint [8] 0 0
First dose of study drug through at least 30 days after last dose of study drug.
Secondary outcome [9] 0 0
Part 1 and Part 3: Clinical benefit rate (CBR, defined as CR, PR or SD)
Timepoint [9] 0 0
First dose of study drug through at least 30 days after last dose of study drug.
Secondary outcome [10] 0 0
Part 1 and Part 3: Progression-free survival (PFS)
Timepoint [10] 0 0
First dose of study drug through at least 30 days after last dose of study drug.
Secondary outcome [11] 0 0
Part 1, Part 2 and Part 3: Duration of objective response (DOR)
Timepoint [11] 0 0
First dose of study drug through at least 30 days after last dose of study drug.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/12/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/03/2022
Sample size
Target
Accrual to date
Final
182
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital /ID# 167386 - Blacktown
Recruitment hospital [2] 0 0
St Vincent's Hospital Melbourne /ID# 167552 - Fitzroy Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research /ID# 170797 - Nedlands
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy Melbourne
Recruitment postcode(s) [3] 0 0
6000 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Virginia
Country [6] 0 0
Austria
State/province [6] 0 0
Steiermark
Country [7] 0 0
Belgium
State/province [7] 0 0
Antwerpen
Country [8] 0 0
Belgium
State/province [8] 0 0
Oost-Vlaanderen
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Finland
State/province [10] 0 0
Pirkanmaa
Country [11] 0 0
Finland
State/province [11] 0 0
Helsinki
Country [12] 0 0
France
State/province [12] 0 0
Gironde
Country [13] 0 0
France
State/province [13] 0 0
Herault
Country [14] 0 0
France
State/province [14] 0 0
Rhone
Country [15] 0 0
France
State/province [15] 0 0
Val-de-Marne
Country [16] 0 0
Japan
State/province [16] 0 0
Chiba
Country [17] 0 0
Japan
State/province [17] 0 0
Fukuoka
Country [18] 0 0
Japan
State/province [18] 0 0
Tokyo
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Spain
State/province [20] 0 0
Valencia
Country [21] 0 0
Taiwan
State/province [21] 0 0
Taipei City

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03000257
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03000257