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Advanced Solid TumorsPhase 1NCT03000257

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

A Phase 1 study testing Venetoclax, Rovalpituzumab Tesirine and ABBV-181 in people with Advanced Solid Tumors, run by AbbVie at 26 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
Venetoclax, Rovalpituzumab Tesirine and ABBV-181
Could I receive a placebo?
No, everyone receives an active treatment
How many people
182 participants
Where
26 sitesin 10 countries
Study dates
14 Dec 2016to 29 Mar 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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)

Trial locations and contacts

26 sites in 10 countries.

26 sites in 10 countries

United States5 sites

  • The University of Chicago Medical Center /ID# 157375

    Chicago, Illinois, 60637-1443

  • Virginia Cancer Specialists - Fairfax /ID# 157377

    Fairfax, Virginia, 22031

  • Carolina BioOncology Institute /ID# 157376

    Huntersville, North Carolina, 28078

  • Moores Cancer Center at UC San Diego /ID# 157374

    La Jolla, California, 92093

  • South Texas Accelerated Research Therapeutics /ID# 157378

    San Antonio, Texas, 78229

Other trials in United States

France4 sites

  • Institut Bergonie /ID# 162662

    Bordeaux, Gironde, 33000

  • Centre Leon Berard /ID# 162660

    Lyon, Rhone, 69373

  • Institut du Cancer de Montpellier - Val d'Aurelle /ID# 163999

    Montpellier, Herault, 34298

  • Institut Gustave Roussy /ID# 162753

    Villejuif, Val-de-Marne, 94805

Other trials in France

Australia3 sites

  • Blacktown Hospital /ID# 167386

    Blacktown, New South Wales, 2148

  • St Vincent's Hospital Melbourne /ID# 167552

    Fitzroy Melbourne, Victoria, 3065

  • Linear Clinical Research /ID# 170797

    Nedlands, Western Australia, 6000

Other trials in Australia

Japan3 sites

  • National Cancer Center Hospital /ID# 166279

    Chuo-ku, Tokyo, 104-0045

  • National Hospital Organization Kyushu Cancer Center /ID# 206229

    Fukuoka, Fukuoka, 811-1395

  • National Cancer Center Hospital East /ID# 166433

    Kashiwa-shi, Chiba, 277-8577

Other trials in Japan

Spain3 sites

  • Hospital Universitario Fundacion Jimenez Diaz /ID# 163862

    Madrid, 28040

  • Hospital Universitario HM Sanchinarro /ID# 163861

    Madrid, 28050

  • Hospital Clinico Universitario de Valencia /ID# 163925

    Valencia, 46010

Other trials in Spain

Belgium2 sites

  • Universitair Ziekenhuis Antwerpen /ID# 170702

    Edegem, Antwerpen, 2650

  • UZ Gent /ID# 170881

    Ghent, Oost-Vlaanderen, 9000

Other trials in Belgium

Finland2 sites

  • Docrates Cancer Center /ID# 166838

    Helsinki, 00180

  • Tampere University Hospital /ID# 166839

    Tampere, Pirkanmaa, 33520

Other trials in Finland

Taiwan2 sites

  • National Taiwan University Hospital /ID# 163997

    Taipei, 100

  • Taipei Medical University Hospital /ID# 163998

    Taipei, 11031

Other trials in Taiwan

Austria1 site

  • Medizinische Universitaet Graz /ID# 168752

    Graz, Styria, 8036

Other trials in Austria

Canada1 site

  • Cross Cancer Institute /ID# 167603

    Edmonton, Alberta, T6G 1Z2

Other trials in Canada

About this study

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

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.

Being tested
Venetoclax, Rovalpituzumab Tesirine, ABBV-181
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
Medical subject headings
Neoplasms, Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Ovarian Neoplasms, Carcinoma, Hepatocellular, Stomach Neoplasms, Small Cell Lung Carcinoma, Mesothelioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VenetoclaxDrug

    Tablet taken orally

  • Rovalpituzumab TesirineDrug

    Intravenous infusion

  • ABBV-181Drug

    Also called Budigalimab

    Intravenous infusion

Study groups in NCT03000257
Study groupRoleWhat they receive
ABBV-181 plus VenetoclaxExperimentalVenetoclax 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.
Receives: Drug: Venetoclax; Drug: ABBV-181
ABBV-181ExperimentalABBV-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.
Receives: Drug: ABBV-181
ABBV-181 plus Rovalpituzumab TesirineExperimentalRovalpituzumab Tesirine will be given once every six weeks times two doses and ABBV-181 will be administered every 3 weeks.
Receives: Drug: Rovalpituzumab Tesirine; Drug: ABBV-181

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: 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.

    Measured: Up to 6 months

  2. Part 1: 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.

    Measured: Up to 6 months

  3. Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab

    Terminal phase elimination half-life (t1/2) of Budigalimab

    Measured: Up to 4 Weeks

  4. Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab

    Maximum Serum Concentration (Cmax) of Budigalimab

    Measured: Up to 12 Weeks

  5. Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab

    Time to maximum plasma concentration of Budigalimab

    Measured: Up to 12 Weeks

  6. Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab

    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab

    Measured: Up to 12 Weeks

  7. Part 2: 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.

    Measured: Up to 6 Months

  8. Part 3: 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.

    Measured: Up to 6 Months

  9. Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax

    Maximum Serum Concentration (Cmax) for Venetoclax

    Measured: Up to 12 Weeks

  10. Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax

    Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24)) of Venetoclax

    Measured: Up to 12 Weeks

  11. Part 3: Time to Cmax (Tmax) of Venetoclax

    Time to maximum plasma concentration of of Venetoclax

    Measured: Up to 12 Weeks

  12. Part 1, Part 2, Part 3: Number of Participants with Adverse Events

    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.

    Measured: From first dose of study drug until 90 days following last dose of study drug (up to 24 months)

Secondary outcomes (11)

  1. Part 2: Terminal Half-life (t1/2) of Budigalimab

    Terminal phase elimination half-life (t1/2) of Budigalimab

    Measured: Up to 4 Weeks

  2. Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine

    Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine

    Measured: Up to 4 Weeks

  3. Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine

    Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine

    Measured: Up to 12 Weeks

  4. Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine

    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Rovalpituzumab Tesirine

    Measured: Up to 12 Weeks

  5. Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab

    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab

    Measured: Up to 12 Weeks

  6. Part 2: Time to Cmax (Tmax) of Budigalimab

    Time to maximum plasma concentration of Budigalimab

    Measured: Up to 12 Weeks

  7. Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine

    Time to maximum plasma concentration of Rovalpituzumab Tesirine

    Measured: Up to 12 Weeks

  8. Part 1 and Part 3: Objective response rate (ORR)

    ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.

    Measured: First dose of study drug through at least 30 days after last dose of study drug.

  9. Part 1 and Part 3: 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.

    Measured: First dose of study drug through at least 30 days after last dose of study drug.

  10. Part 1 and Part 3: 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.

    Measured: First dose of study drug through at least 30 days after last dose of study drug.

  11. Part 1, Part 2 and Part 3: 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.

    Measured: First dose of study drug through at least 30 days after last dose of study drug.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2016 (estimated)
  2. Study start14 Dec 2016
  3. Primary completion29 Mar 2022
  4. Study completion29 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
182 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03000257
Sponsor's protocol ID
M15-891
Other IDs
2016-002520-89, 2016
Status last verified
Apr 2022
First submitted
15 Dec 2016
Last updated
14 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 35034046

  • 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.

    PubMed 34329846

  • 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.

    PubMed 34216247

  • 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.

    PubMed 32770720

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, Rovalpituzumab Tesirine and ABBV-181 in people with Advanced Solid Tumors, run by AbbVie at 26 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, France, Australia, Japan, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab (time frame: Up to 6 months). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03000257, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2022.

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