Description:
This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and
pharmacodynamics of ABBV-927, and to determine the maximum tolerated dose (MTD) or
recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as
combination therapy with ABBV-181 in participants with advanced solid tumors.
Title
- Brief Title: A Study of ABBV-927 and ABBV-181, an Immunotherapy, in Participants With Advanced Solid Tumors
- Official Title: A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-927 and ABBV-181, an Immunotherapy, in Subjects With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
M15-862
- SECONDARY ID:
2016-002219-16
- NCT ID:
NCT02988960
Conditions
- Advanced Solid Tumors Cancer
Interventions
Drug | Synonyms | Arms |
---|
ABBV-927 | | Escalating Arm 1: ABBV-927 |
ABBV-927 | | Escalating Arm 2: ABBV-927 |
ABBV-181 | Budigalimab | Escalating Arm 3: ABBV-927+ABBV-181 |
Purpose
This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and
pharmacodynamics of ABBV-927, and to determine the maximum tolerated dose (MTD) or
recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as
combination therapy with ABBV-181 in participants with advanced solid tumors.
Trial Arms
Name | Type | Description | Interventions |
---|
Escalating Arm 1: ABBV-927 | Experimental | Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927. | |
Escalating Arm 2: ABBV-927 | Experimental | Participants with solid tumors will receive escalating intratumoral (IT) doses of ABBV-927. | |
Escalating Arm 3: ABBV-927+ABBV-181 | Experimental | Participants with Non-Small Cell Lung Cancer (NSCLC) will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181. | |
Escalating Arm 4: ABBV-927+ABBV-181 | Experimental | Participants with Head and Neck Squamous Cell Carcinoma (HNSCC) will receive escalating IT doses of ABBV-927 and IV doses of ABBV-181. | |
Escalating Arm 5 (Japan): ABBV-927 | Experimental | Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927. | |
Escalating Arm 6 (Japan): ABBV-927+ABBV-181 | Experimental | Participants with solid tumors will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181. | |
Expansion Arm A: ABBV-927 | Experimental | Additional participants with HNSCC or NSCLC will receive intravenous (IV) doses of ABBV-927. | |
Expansion Arm B: ABBV-927+ABBV-181 | Experimental | Additional participants with HNSCC will receive IT doses of ABBV-927 and IV doses of ABBV-181. | |
Expansion Arm C: ABBV-927+ABBV-181 | Experimental | Additional participants with NSCLC will receive IV doses of ABBV-927 and IV doses of ABBV-181. | |
Eligibility Criteria
Inclusion Criteria:
- Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0
to 1.
- Participants have adequate bone marrow, kidney and liver function.
- Participants with a history of chronic heart failure or significant cardiovascular
disease must have an echocardiogram or multigated acquisition scan indicating left
ventricular ejection fraction greater than or equal to 45% within 28 days prior to the
first dose of study drug.
- Participants must have creatinine clearance greater than or equal to 50 mL/min as
measured by 24-hour urine or estimated by the Cockcroft-Gault formula.
- Participants must have total bilirubin less than or equal to 1.5 times the upper limit
of normal (ULN), and aspartate aminotransferase and alanine aminotransferase less than
or equal to 2.5 times ULN.
- Participants in all monotherapy arms must have an advanced solid tumor that has
progressed on standard therapies known to provide clinical benefit or the participants
are intolerant to such therapies.
- Participants in all combination therapy arms must have recurrent or metastatic HNSCC
or NSCLC and previously received platinum-based therapy and progressed either during
or after anti-programmed death ligand 1 (PDL1)-based therapy. In addition,
participants must have received only one prior immunotherapy.
- The Sponsor may decide to limit the specific tumor types selected or treatment
settings for specific arms based on evidence gathered.
Exclusion Criteria:
- Participant must not have an active or prior documented autoimmune disease in the last
2 years.
- Participant must not have current or prior use of immunosuppressive medication within
14 days prior to the first dose (with certain exceptions).
- Participant must not have a history of primary immunodeficiency, bone marrow
transplantation, chronic lymphocytic leukemia, solid organ transplantation, previous
clinical diagnosis of tuberculosis, inflammatory bowel disease, interstitial lung
disease, or immune-mediated pneumonitis.
- Participant must not have a history of clinically significant uncontrolled
condition(s) including but not limited to the following: uncontrolled hypertension;
symptomatic congestive heart failure; unstable angina pectoris or cardiac arrhythmia
including atrial fibrillation.
- Participant must not have a history of coagulopathy or a platelet disorder associated
with significant clinical risk of thromboembolic event in the judgement of the
investigator, or major thromboembolic event within 6 months prior to the first dose of
study treatment.
- Participant must not have a prior grade greater than or equal to 3 immune-mediated
neurotoxicity or pneumonitis while receiving immunotherapy.
- Participant must not have a known uncontrolled malignancy of the central nervous
system.
- Participants in all combination therapy arms must not have a history of exposure to an
immunotherapy experiencing an immune-mediated adverse event that required permanent
discontinuation of the immunotherapy.
- Female participants must not be pregnant, breastfeeding or considering becoming
pregnant during the study or for at least 3 or 5 months (for monotherapy and
combination therapy participants, respectively) after the last dose of study drug.
- Male participants must not be considering fathering a child or donating sperm during
the study or for at least 3 or 5 months (for monotherapy and combination therapy
participants, respectively) after the last dose of study drug.
- Participant is judged by the investigator to have evidence of hemolysis.
- For Japan only, participants with a history of interstitial lung disease (pneumonitis)
or current interstitial lung disease (pneumonitis).
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 |
Time Frame: | Up to 8 weeks |
Safety Issue: | |
Description: | The MTD and the RPTD of ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 will be determined during the dose escalation phase of the study. Once the RPTD has been determined, the dose expansion portion will begin. |
Secondary Outcome Measures
Measure: | Clinical benefit rate (CBR, defined as the percentage of participants with a confirmed partial, complete response, or stable disease for at least 24 weeks to the treatment) |
Time Frame: | Up to 30 days after and up to 24-month of treatment period |
Safety Issue: | |
Description: | CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease for at least 24 weeks to the treatment. |
Measure: | Duration of objective response (DOR) |
Time Frame: | Up to 30 days after and up to 24-month of treatment period |
Safety Issue: | |
Description: | DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first. |
Measure: | Objective response rate (ORR) |
Time Frame: | Up to 30 days after and up to 24-month of treatment period |
Safety Issue: | |
Description: | ORR is defined as the proportion of participants with a confirmed partial or complete response to the treatment. |
Measure: | Progression-free survival (PFS) |
Time Frame: | Up to 30 days after and up to 24-month of treatment period |
Safety Issue: | |
Description: | PFS time is defined as the time from the first dose of ABBV-927 to disease progression or death, whichever occurs first. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | AbbVie |
Trial Keywords
- Non-small cell lung cancer (NSCLC)
- Squamous cell carcinoma of the head and neck (SCCHN)
- Advanced solid tumor
- Cancer
- Pancreatic adenocarcinoma
- Cutaneous melanoma
- ABBV-927
- ABBV-181
- Budigalimab
Last Updated
August 11, 2021