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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 : September 11, 2020
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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 182 participants
Allocation: Non-Randomized
Intervention Model: Single Group 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 : March 4, 2021
Estimated Study Completion Date : March 4, 2021


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

  2. 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.

  3. 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.

  4. Terminal Half-life (t1/2) [ Time Frame: Up to 4 Weeks ]
  5. Maximum Observed Serum Concentration (Cmax) [ Time Frame: Up to 12 Weeks ]
  6. Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt)

  7. Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) [ 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))

  8. 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) ]
  9. Time to Cmax (Tmax) [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration

  10. 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.

  11. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  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.

  4. 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.


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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, 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.

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
Show Show 26 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
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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: September 11, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Neoplasms
Venetoclax
Antineoplastic Agents