Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03000257
Recruitment Status : Active, not recruiting
First Posted : December 22, 2016
Last Update Posted : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: Venetoclax Drug: Rovalpituzumab Tesirine Drug: ABBV-181 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 182 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 14, 2016
Estimated Primary Completion Date : May 5, 2022
Estimated Study Completion Date : May 5, 2022


Arm Intervention/treatment
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.
Drug: Venetoclax
Tablet taken orally

Drug: ABBV-181
Intravenous infusion
Other Name: Budigalimab

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.
Drug: ABBV-181
Intravenous infusion
Other Name: Budigalimab

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.
Drug: Rovalpituzumab Tesirine
Intravenous infusion

Drug: ABBV-181
Intravenous infusion
Other Name: Budigalimab




Primary Outcome Measures :
  1. Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab [ Time Frame: Up to 6 months ]
    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.

  2. Part 1: Maximum tolerated dose (MTD) of Budigalimab [ Time Frame: Up to 6 months ]
    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.

  3. Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab [ Time Frame: Up to 4 Weeks ]
    Terminal phase elimination half-life (t1/2) of Budigalimab

  4. Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Maximum Serum Concentration (Cmax) of Budigalimab

  5. Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration of Budigalimab

  6. Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab

  7. Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination [ Time Frame: Up to 6 Months ]
    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.

  8. Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination. [ Time Frame: Up to 6 Months ]
    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.

  9. Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax [ Time Frame: Up to 12 Weeks ]
    Maximum Serum Concentration (Cmax) for Venetoclax

  10. Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24)) of Venetoclax

  11. Part 3: Time to Cmax (Tmax) of Venetoclax [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration of of Venetoclax

  12. Part 1, Part 2, Part 3: Number of Participants with Adverse Events [ Time Frame: From first dose of study drug until 90 days following last dose of study drug (up to 24 months) ]
    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.


Secondary Outcome Measures :
  1. Part 2: Terminal Half-life (t1/2) of Budigalimab [ Time Frame: Up to 4 Weeks ]
    Terminal phase elimination half-life (t1/2) of Budigalimab

  2. Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine [ Time Frame: Up to 4 Weeks ]
    Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine

  3. Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine [ Time Frame: Up to 12 Weeks ]
    Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine

  4. Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Rovalpituzumab Tesirine

  5. Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab

  6. Part 2: Time to Cmax (Tmax) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration of Budigalimab

  7. Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration of Rovalpituzumab Tesirine

  8. Part 1 and Part 3: Objective response rate (ORR) [ Time Frame: First dose of study drug through at least 30 days after last dose of study drug. ]
    ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.

  9. Part 1 and Part 3: Clinical benefit rate (CBR, defined as CR, PR or SD) [ Time Frame: First dose of study drug through at least 30 days after last dose of study drug. ]
    CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.

  10. Part 1 and Part 3: Progression-free survival (PFS) [ Time Frame: First dose of study drug through at least 30 days after last dose of study drug. ]
    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.

  11. Part 1, Part 2 and Part 3: Duration of objective response (DOR) [ Time Frame: First dose of study drug through at least 30 days after last dose of study drug. ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03000257


Locations
Hide Hide 26 study locations
Layout table for location information
United States, California
Moore UC San Diego Cancer Center /ID# 157374
La Jolla, California, United States, 92093
United States, Illinois
The University of Chicago Medical Center /ID# 157375
Chicago, Illinois, United States, 60637-1443
United States, North Carolina
Carolina BioOncology Institute /ID# 157376
Huntersville, North Carolina, United States, 28078
United States, Texas
South Texas Accelerated Research Therapeutics /ID# 157378
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Cancer Specialists /ID# 157377
Fairfax, Virginia, United States, 22031
Australia, New South Wales
Blacktown Hospital /ID# 167386
Blacktown, New South Wales, Australia, 2148
Australia, Victoria
St. Vincents Hosp Melbourne /ID# 167552
Fitzroy, Victoria, Australia, 3065
Australia, Western Australia
Linear Clinical Research /ID# 170797
Perth, Western Australia, Australia, 6000
Austria
LKH-Univ. Klinikum Graz /ID# 168752
Graz, Austria, 8036
Belgium
UZ Ghent /ID# 170881
Ghent, Oost-Vlaanderen, Belgium, 9000
UZ Antwerpen /ID# 170702
Edegem, Belgium, 2650
Canada, Alberta
Cross Cancer Institute /ID# 167603
Edmonton, Alberta, Canada, T6G 1Z2
Finland
Docrates Cancer Center /ID# 166838
Helsinki, Finland, 00180
Tampere University Hospital /ID# 166839
Tampere, Finland, 33521
France
Institut Bergonie /ID# 162662
Bordeaux, Gironde, France, 33000
Institut Regional du Cancer /ID# 163999
Montpellier CEDEX 5, Herault, France, 34298
Centre Leon Berard /ID# 162660
Lyon CEDEX 08, Rhone, France, 69373
Institut Gustave Roussy /ID# 162753
Villejuif Cedex, Val-de-Marne, France, 94805
Japan
National Cancer Center Hospital East /ID# 166433
Kashiwa-shi, Chiba, Japan, 277-8577
National Hospital Organization Kyushu Cancer Center /ID# 206229
Fukuoka-shi, Fukuoka, Japan, 811-1395
National Cancer Center Hospital /ID# 166279
Chuo-ku, Tokyo, Japan, 104-0045
Spain
Hospital Universitario Fundacion Jimenez Diaz /ID# 163862
Madrid, Spain, 28040
Hospital Universitario HM Sanchinarro /ID# 163861
Madrid, Spain, 28050
Hospital Clinico Universitario de Valencia /ID# 163925
Valencia, Spain, 46010
Taiwan
National Taiwan Univ Hosp /ID# 163997
Taipei City, Taipei, Taiwan, 10002
Taipei Medical University Hospital /ID# 163998
Taipei City, Taiwan, 11031
Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: ABBVIE INC. AbbVie
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03000257    
Other Study ID Numbers: M15-891
2016-002520-89 ( EudraCT Number )
First Posted: December 22, 2016    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Venetoclax
Antineoplastic Agents