Small Cell Lung Cancer
Conditions
Keywords
Cancer, Small Cell Lung Cancer, Small Cell Lung Carcinoma
Brief summary
This is a multicenter, open-label, Phase 1 study of ABBV-011 given as a single agent and in combination with budigalimab (ABBV-181) in participants with relapsed or refractory small cell lung cancer (SCLC). The study consists of 4 parts: Part A is a single-agent ABBV-011 dose regimen finding cohort; followed by Part B, a single-agent ABBV-011 dose expansion cohort; and then Part C, an ABBV-011 and budigalimab (ABBV-181) combination escalation and expansion cohort; Part D, single-agent ABBV-011 dose-evaluating cohort for Japan.
Interventions
DRUGABBV-011
Intravenous
DRUGBudigalimab
Intravenous
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
* Histologically or cytologically confirmed small cell lung cancer (SCLC) that is relapsed or refractory following at least 1 prior platinum-containing chemotherapy, but no more than 3 total prior lines of therapy, and with no curative therapy available. * Measurable disease, defined as at least 1 tumor lesion greater than or equal to 10 mm in the longest diameter or a lymph node greater than or equal to 15 mm in short axis measurement assessed by computed tomography (CT) scan, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Minimum life expectancy of at least 12 weeks. * Recovery to at least Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration. * Adequate hematologic, hepatic, neurologic, and renal function. * All participants in Part B and Part C will be required to have tumor tissue that tests positive for target expression. * Sponsor may elect for confirmed SCLC tumor tissue to test positive for target expression for Parts A and D participants as well. * Last dose of any prior anticancer therapy \>= 4 weeks before the first dose of study drug. Additional Inclusion Criteria for Study Part B and Part C: * SCLC tumor tissue that tests positive for seizure-related homolog 6 (SEZ6) by immunohistochemistry (IHC).
Exclusion criteria
* History of confirmed or suspected liver cirrhosis, hepatic veno-occlusive disease (VOD), sinusoidal obstruction syndrome (SOS), alcohol dependence, or ongoing excessive alcohol use. * Prior history of allogeneic or autologous stem cell transplantation. * Documented history of stroke or clinically significant cardiac disease as described in the protocol within 6 months prior to the first dose of study drug. * History of cardiac conduction abnormalities as described in the protocol. * Recent or ongoing serious infection, as described in the protocol. * Active SARS-CoV-2 infection. * Prior or concomitant malignancies with some exceptions, as described in the protocol. * Any significant medical or psychiatric condition, including any suggested by Screening laboratory findings, that in the opinion of the Investigator or Sponsor may place the participant at undue risk from the study treatment, interfere with interpretation of study results, or compromise ability to comply with protocol requirements. * Participants with a history of hypersensitivity to the active ingredients or any excipients of study drugs (ABBV-011 or budigalimab \[ABBV-181\]) will be excluded. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to approximately 5 years after the first participant receives first dose of study drug | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. |
| Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | The Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of ABBV-011 will be determined during the Part A dose escalation cohort. |
| Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of ABBV-011 in Combination with Budigalimab | Up to approximately 5 years after the first participant receives first dose of study drug | The Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of ABBV-011 in combination with budigalimab will be determined during the Part C dose escalation cohort. |
| Number of Participants With Dose Limiting Toxicities (DLTs) | Up to approximately 5 years after the first participant receives first dose of study drug | DLTs are adverse events as described in the protocol. |
| Mean Change from Baseline in Vital Signs | Up to approximately 5 years after the first participant receives first dose of study drug | Mean change from Baseline in vital signs like blood pressure will be assessed. |
| Incidence of Laboratory Abnormaities | Up to approximately 5 years after the first participant receives first dose of study drug | Number of participants with lab abnormalities will be assessed. |
| Mean Change from Baseline in Electrocardiogram (ECG) Parameters | Up to approximately 5 years after the first participant receives first dose of study drug | Mean change from Baseline in ECG parameters like QTc interval will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Clearance (CL) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Serum clearance of ABBV011. |
| Steady State Volume of Distribution (Vss) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Steady state volume of distribution (Vss) of ABBV-011. |
| Incidence of Antidrug Antibodies (ADA) Against ABBV-011 or Budigalimab (ABBV-181) | Up to approximately 5 years after the first participant receives first dose of study drug | Number of participants with incidence of ADAs against ABBV-011 or budigalimab will be assessed. |
| Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) | Up to approximately 5 years after the first participant receives first dose of study drug | ORR is defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR). |
| Maximum Serum Concentration (Cmax) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Maximum Serum Concentration (Cmax) of ABBV-011. |
| Duration of Response (DOR) | Up to approximately 5 years after the first participant receives first dose of study drug | DOR is defined as the time from the participant's initial objective response (CR or PR) to Progressive Disease (PD) or death due to any cause, whichever occurs first. |
| Duration of Clinical Benefit (DOCB) | Up to approximately 5 years after the first participant receives first dose of study drug | (DOCB) is defined as the time from the participant's initial observation of clinical benefit (CR or PR or SD) to PD or death due to any cause, whichever occurs first. |
| Progression-Free Survival (PFS) | Up to approximately 5 years after the first participant receives first dose of study drug | PFS time is defined as the time from the subject's first dose of study drug (Day 1) to either the subject's disease progression (PD) or death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to approximately 5 years after the first participant receives first dose of study drug | OS is defined as the time from the subject's first dose date to death due to any cause. |
| Clinical Benefit Rate (CBR) | Up to approximately 5 years after the first participant receives first dose of study drug | CBR is defined as the percentage of participants with best overall response (confirmed or unconfirmed) of CR, PR or stable disease (SD). |
| Area Under the Serum Concentration-Time Curve (AUCinf) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Area under the serum concentration-time curve within a dosing interval of ABBV-011. |
| Area Under the Serum Concentration-Time Curve within a Dosing Interval (AUC0-t) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Area under the serum concentration-time curve within a dosing interval (AUC0-t) of ABBV-011. |
| Time to Maximum Serum Concentration (Tmax) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Time to maximum serum concentration (Tmax) of ABBV-011. |
| Observed Serum Concentration at Trough (Ctrough) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Observed serum concentration at trough (Ctrough) of ABBV-011. |
| Apparent Terminal Half-Life (T1/2) of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Apparent terminal half-life (T1/2) of ABBV-011. |
| Accumulation Ratio of ABBV-011 | Up to approximately 5 years after the first participant receives first dose of study drug | Accumulation ratio of ABBV-011. |
Countries
Japan, South Korea, Taiwan, United States
Outcome results
None listed