Clinical trial NCT03639194: A Study of ABBV-011 Alone and in Combination With Budigalimab (ABBV-181) in Participants With Relapsed or Refractory Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Keywords: Cancer
Small Cell Lung Cancer
Small Cell Lung Carcinoma
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2018-08-21
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of ABBV-011 in Combination with Budigalimab
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Mean Change from Baseline in Vital Signs
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Incidence of Laboratory Abnormaities
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Mean Change from Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Area Under the Serum Concentration-Time Curve (AUCinf) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Area Under the Serum Concentration-Time Curve within a Dosing Interval (AUC0-t) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Time to Maximum Serum Concentration (Tmax) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Observed Serum Concentration at Trough (Ctrough) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Apparent Terminal Half-Life (T1/2) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Accumulation Ratio of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Serum Clearance (CL) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Steady State Volume of Distribution (Vss) of ABBV-011
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Incidence of Antidrug Antibodies (ADA) Against ABBV-011 or Budigalimab (ABBV-181)
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Duration of Response (DOR)
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Duration of Clinical Benefit (DOCB)
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years after the first participant receives first dose of study drug
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Main /ID# 207295
state: Alabama
city: Springdale
country: United States
facility: Highlands Oncology Group, PA /ID# 207176
state: Arkansas
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center /ID# 207548
state: California
city: New Haven
country: United States
facility: Yale School of Medicine /ID# 207559
state: Connecticut
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics /ID# 207560
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center /ID# 208217
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 207549
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 213032
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center /ID# 207177
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital /ID# 233539
state: Michigan
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 207168
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 208216
state: New York
city: Durham
country: United States
facility: Duke Cancer Center /ID# 207547
state: North Carolina
city: Cleveland
country: United States
facility: UH Cleveland Medical Center /ID# 207561
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University /ID# 207552
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC /ID# 207175
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center /ID# 207551
state: Tennessee
city: San Antonio
country: United States
facility: NEXT Oncology /ID# 207167
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah /ID# 207553
state: Utah
city: Seattle
country: United States
facility: University of Washington /ID# 207557
state: Washington
city: Madison
country: United States
facility: Univ of Wisconsin Hosp/Clinics /ID# 207556
state: Wisconsin
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 230943
state: Chiba
city: Matsuyama-shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center /ID# 229737
state: Ehime
city: Sapporo-shi
country: Japan
facility: Hokkaido Cancer Center /ID# 229101
state: Hokkaido
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center /ID# 230911
state: Shizuoka
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital /ID# 229111
state: Wakayama
city: Goyang
country: Korea, Republic of
facility: National Cancer Center /ID# 240169
state: Gyeonggido
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital /ID# 234274
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 239515
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 234272
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 234273
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 234267
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Wiedemeyer WR, Gavrilyuk J, Schammel A, Zhao X, Sarvaiya H, Pysz M, Gu C, You M, Isse K, Sullivan T, French D, Lee C, Dang AT, Zhang Z, Aujay M, Bankovich AJ, Vitorino P. ABBV-011, A Novel, Calicheamicin-Based Antibody-Drug Conjugate, Targets SEZ6 to Eradicate Small Cell Lung Cancer Tumors. Mol Cancer Ther. 2022 Jun 1;21(6):986-998. doi: 10.1158/1535-7163.MCT-21-0851.