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

Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03639194
• Other study ID #: M17-327
• Status: Completed
• Phase: Phase 1
• Start date: October 24, 2018
• Est. completion date: January 25, 2024

Study information

• Verified date: February 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: January 25, 2024
• Est. primary completion date: January 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• ABBV-011
Intravenous
• Budigalimab
Intravenous

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East /ID# 230943	Kashiwa-shi	Chiba
Japan	National Hospital Organization Shikoku Cancer Center /ID# 229737	Matsuyama-shi	Ehime
Japan	Hokkaido Cancer Center /ID# 229101	Sapporo-shi	Hokkaido
Japan	Shizuoka Cancer Center /ID# 230911	Sunto-gun	Shizuoka
Japan	Wakayama Medical University Hospital /ID# 229111	Wakayama-shi	Wakayama
Korea, Republic of	National Cancer Center /ID# 240169	Goyang	Gyeonggido
Korea, Republic of	Seoul National University Bundang Hospital /ID# 234274	Seongnam	Gyeonggido
Korea, Republic of	Asan Medical Center /ID# 234273	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 234272	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital /ID# 239515	Seoul	Seoul Teugbyeolsi
Taiwan	National Cheng Kung University Hospital /ID# 234267	Tainan
United States	University of Michigan Comprehensive Cancer Center /ID# 207177	Ann Arbor	Michigan
United States	University of Alabama at Birmingham - Main /ID# 207295	Birmingham	Alabama
United States	Dana-Farber Cancer Institute /ID# 213032	Boston	Massachusetts
United States	Massachusetts General Hospital /ID# 207549	Boston	Massachusetts
United States	UH Cleveland Medical Center /ID# 207561	Cleveland	Ohio
United States	The Ohio State University /ID# 207552	Columbus	Ohio
United States	Henry Ford Hospital /ID# 233539	Detroit	Michigan
United States	Duke Cancer Center /ID# 207547	Durham	North Carolina
United States	University of Iowa Hospitals and Clinics /ID# 207560	Iowa City	Iowa
United States	University of Kentucky Chandler Medical Center /ID# 208217	Lexington	Kentucky
United States	Univ of Wisconsin Hosp/Clinics /ID# 207556	Madison	Wisconsin
United States	Tennessee Oncology, PLLC /ID# 207175	Nashville	Tennessee
United States	Vanderbilt Ingram Cancer Center /ID# 207551	Nashville	Tennessee
United States	Yale School of Medicine /ID# 207559	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 208216	New York	New York
United States	University of California, Davis Comprehensive Cancer Center /ID# 207548	Sacramento	California
United States	Washington University-School of Medicine /ID# 207168	Saint Louis	Missouri
United States	University of Utah /ID# 207553	Salt Lake City	Utah
United States	NEXT Oncology /ID# 207167	San Antonio	Texas
United States	University of Washington /ID# 207557	Seattle	Washington
United States	Highlands Oncology Group, PA /ID# 207176	Springdale	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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