A Study of ABBV-011 Alone and in Combination With Budigalimab (ABBV-181) in Participants With Relapsed or Refractory Small Cell Lung Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Study of ABBV-011 as a Single-Agent and in Combination With Budigalimab (ABBV-181) in Subjects With Relapsed or Refractory Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: ABBV-011
* Drug: Budigalimab


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria for Part C: History of inflammatory bowel disease. Peripheral neuropathy Grade 2 with pain, or Grade 3 or higher. Body weight less than 35 kilograms. Active pneumonitis or interstitial lung disease (ILD) or a history of pneumonitis/ILD requiring treatment with steroids. Participants previously treated with an anti PD-1/PD-L1 targeting agent must meet additional criteria described in the protocol. Participant is judged by the Investigator to have evidence of ongoing hemolysis. Immunosuppressive use with exceptions as per protocol. Participants who have received a live vaccine within 30 days of start of study treatment. Active autoimmune disease with exceptions as indicated in the protocol. History of primary immunodeficiency, solid organ transplantation, or previous clinical diagnosis of tuberculosis. Participants with a history of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS). Additional exclusion criteria for Japanese and Korean participants: - Participants with a history of interstitial lung disease (pneumonitis) or current interstitial lung disease (pneumonitis).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: ABBV-011 Dose Escalation<br>ABBV-011 via intravenous administration at various doses and dosing regimens until the maximum tolerated dose and/or the recommended Part B dose(s) is declared. | Drug: ABBV-011<br>* Intravenous<br>* Other names: SC-011;|
| Experimental: Part B: ABBV-011 Dose Expansion<br>ABBV-011 via intravenous administration at dose regimen(s) that will not exceed the maximum tolerated dose determined in Part A. | Drug: ABBV-011<br>* Intravenous<br>* Other names: SC-011;|
| Experimental: Part C: ABBV-011 + Budigalimab Escalation and Expansion<br>ABBV-011 via intravenous administration at various doses and dosing regimens starting at least 1 dose level below the recommended single-agent dose of ABBV-011 for Part B plus Budigalimab via intravenous administration at fixed doses and various dosing regimens. | Drug: ABBV-011<br>* Intravenous<br>* Other names: SC-011;Drug: Budigalimab<br>* Intravenous<br>* Other names: ABBV-181;|
| Experimental: Part D: ABBV-011 Dose Evaluation for Japan<br>ABBV-011 via intravenous administration will be administered every 3 weeks (Q3wk), on Day 1 of each 21-day cycle or alternate dosing regimens. | Drug: ABBV-011<br>* Intravenous<br>* Other names: SC-011;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | 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. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of ABBV-011 | 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. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of ABBV-011 in Combination with Budigalimab | 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. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Number of Participants With Dose Limiting Toxicities (DLTs) | DLTs are adverse events as described in the protocol. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Mean Change from Baseline in Vital Signs | Mean change from Baseline in vital signs like blood pressure will be assessed. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Incidence of Laboratory Abnormaities | Number of participants with lab abnormalities will be assessed. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Mean Change from Baseline in Electrocardiogram (ECG) Parameters | Mean change from Baseline in ECG parameters like QTc interval will be assessed. | Up to approximately 5 years after the first participant receives first dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Serum Concentration (Cmax) of ABBV-011 | Maximum Serum Concentration (Cmax) 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 (AUCinf) of ABBV-011 | Area under the serum concentration-time curve within a dosing interval 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 | 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 | 
| Time to Maximum Serum Concentration (Tmax) 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 | 
| Observed Serum Concentration at Trough (Ctrough) 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 | 
| Apparent Terminal Half-Life (T1/2) 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 | 
| Accumulation Ratio of ABBV-011 | Accumulation ratio of ABBV-011. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Serum Clearance (CL) of ABBV-011 | Serum clearance of ABBV011. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Steady State Volume of Distribution (Vss) of ABBV-011 | Steady state volume of distribution (Vss) of ABBV-011. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Incidence of Antidrug Antibodies (ADA) Against ABBV-011 or Budigalimab (ABBV-181) | Number of participants with incidence of ADAs against ABBV-011 or budigalimab will be assessed. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) | ORR is defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR). | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Clinical Benefit Rate (CBR) | CBR is defined as the percentage of participants with best overall response (confirmed or unconfirmed) of CR, PR or stable disease (SD). | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Duration of Response (DOR) | 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. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Duration of Clinical Benefit (DOCB) | (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. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Progression-Free Survival (PFS) | 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. | Up to approximately 5 years after the first participant receives first dose of study drug | 
| Overall Survival (OS) | OS is defined as the time from the subject's first dose date to death due to any cause. | Up to approximately 5 years after the first participant receives first dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Small Cell Lung Cancer, Small Cell Lung Carcinoma