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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03000257
Ethics application status
Date submitted
15/12/2016
Date registered
22/12/2016
Date last updated
4/06/2020

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
Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab - The safety and tolerability of Budigalimab will be assessed in patients with Non-small cell lung cancer (NSCLC) and Squamous cell carcinoma of the head and neck (SCCHN )to determine the RPTD.
Timepoint [1] 0 0
Up to 6 Months
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to 6 Months
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to 6 Months
Primary outcome [4] 0 0
Terminal Half-life (t1/2)
Timepoint [4] 0 0
Up to 4 Weeks
Primary outcome [5] 0 0
Maximum Observed Serum Concentration (Cmax)
Timepoint [5] 0 0
Up to 12 Weeks
Primary outcome [6] 0 0
Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) - Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt)
Timepoint [6] 0 0
Up to 12 Weeks
Primary outcome [7] 0 0
Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) - Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24))
Timepoint [7] 0 0
Up to 12 Weeks
Primary outcome [8] 0 0
Number of Participants with Adverse Events
Timepoint [8] 0 0
From first dose of study drug until 90 days following last dose of study drug (up to 24 months)
Primary outcome [9] 0 0
Time to Cmax (Tmax) - Time to maximum plasma concentration
Timepoint [9] 0 0
Up to 12 Weeks
Primary outcome [10] 0 0
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.
Timepoint [10] 0 0
Up to 6 months
Primary outcome [11] 0 0
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.
Timepoint [11] 0 0
Up to 6 months
Secondary outcome [1] 0 0
Objective response rate (ORR) - ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.
Timepoint [1] 0 0
First dose of study drug through at least 30 days after last dose of study drug.
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
First dose of study drug through at least 30 days after last dose of study drug.
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
First dose of study drug through at least 30 days after last dose of study drug.
Secondary outcome [4] 0 0
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.
Timepoint [4] 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
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participant has received anticancer therapy including chemotherapy, immunotherapy,
radiation therapy, biologic, 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 plus rovalpituzumab tesirine therapy (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.

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
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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. Vincents Hosp Melbourne /ID# 167552 - Fitzroy
Recruitment hospital [3] 0 0
Linear Clinical Research /ID# 170797 - Perth
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
6000 - Perth
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
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
Austria
State/province [7] 0 0
Graz
Country [8] 0 0
Austria
State/province [8] 0 0
Vienna
Country [9] 0 0
Belgium
State/province [9] 0 0
Oost-Vlaanderen
Country [10] 0 0
Belgium
State/province [10] 0 0
Edegem
Country [11] 0 0
Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Finland
State/province [12] 0 0
Helsinki
Country [13] 0 0
Finland
State/province [13] 0 0
Tampere
Country [14] 0 0
France
State/province [14] 0 0
Gironde
Country [15] 0 0
France
State/province [15] 0 0
Herault
Country [16] 0 0
France
State/province [16] 0 0
Rhone
Country [17] 0 0
France
State/province [17] 0 0
Val-de-Marne
Country [18] 0 0
Japan
State/province [18] 0 0
Chiba
Country [19] 0 0
Japan
State/province [19] 0 0
Fukuoka
Country [20] 0 0
Japan
State/province [20] 0 0
Tokyo
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
València
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taipei
Country [24] 0 0
Taiwan
State/province [24] 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/show/NCT03000257
Trial related presentations / publications
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
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
847.283.8955
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

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