Advanced Solid Tumors Cancer
Conditions
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
Brief summary
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.
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events | Up to 30 days after and up to 24-month of treatment period | An adverse event (AE) 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. |
| Time to Cmax (Tmax) of ABBV-181 | Up to 12 weeks after participant's first dose | Time to Cmax (Tmax) of ABBV-181. |
| Maximum observed serum concentration (Cmax) of ABBV-181 | Up to 12 weeks after participant's first dose | Maximum observed serum concentration (Cmax) of ABBV-181. |
| Terminal-Phase Elimination Rate Constant (β) of ABBV-181 | Up to 12 weeks after participant's first dose | Terminal-phase elimination rate constant (β)of ABBV-181. |
| Terminal half-life (t1/2) of ABBV-181 | Up to 4 weeks after participant's first dose | Terminal half-life (t1/2) of ABBV-181. |
| Area under the serum concentration-time curve (AUCt) of ABBV-181 | Up to 12 weeks after participant's first dose | Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-181. |
| Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 | Up to 8 weeks | 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. |
| Time to Cmax (Tmax) of ABBV-927 | Up to 12 weeks after participant's first dose | Time to Cmax (Tmax) of ABBV-927. |
| Maximum observed serum concentration (Cmax) of ABBV-927 | Up to 12 weeks after participant's first dose | Maximum observed serum concentration (Cmax) of ABBV-927. |
| Terminal-Phase Elimination Rate Constant (β) of ABBV-927 | Up to 12 weeks after participant's first dose | Terminal-phase elimination rate constant (β)of ABBV-927. |
| Terminal half-life (t1/2) of ABBV-927 | Up to 4 weeks after participant's first dose | Terminal half-life (t1/2) of ABBV-927. |
| Area under the serum concentration-time curve (AUCt) of ABBV-927 | Up to 12 weeks after participant's first dose | Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-927. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of objective response (DOR) | Up to 30 days after and up to 24-month of treatment period | DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first. |
| Objective response rate (ORR) | Up to 30 days after and up to 24-month of treatment period | ORR is defined as the proportion of participants with a confirmed partial or complete response to the treatment. |
| Progression-free survival (PFS) | Up to 30 days after and up to 24-month of treatment period | PFS time is defined as the time from the first dose of ABBV-927 to disease progression or death, whichever occurs first. |
| 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) | Up to 30 days after and up to 24-month of treatment period | 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. |
Countries
Australia, Canada, France, Japan, South Korea, Spain, United States
Outcome results
None listed