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

• ClinicalTrials.gov Identifier: NCT03639194
• Recruitment Status: Completed
• First Posted: August 21, 2018
• Last Update Posted: February 9, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: August 17, 2018
• First Posted Date: August 21, 2018
• Last Update Posted Date: February 9, 2024
• Actual Study Start Date: October 24, 2018
• Actual Primary Completion Date: January 25, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 31, 2020)

• Number of Participants With Adverse Events [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: August 17, 2018)

MTD and/or RPTD of SC-011 [ Time Frame: Up to approximately 24 months ]

The Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RPTD) of SC-011 will be determined during the Part A dose escalation cohort.

Current Secondary Outcome Measures (submitted: July 13, 2022)

• Maximum Serum Concentration (Cmax) of ABBV-011 [ Time Frame: Up to approximately 5 years after the first participant receives first dose of study drug ]
  Maximum Serum Concentration (Cmax) of ABBV-011.
• Area Under the Serum Concentration-Time Curve (AUCinf) of ABBV-011 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to approximately 5 years after the first participant receives first dose of study drug ]
  Accumulation ratio of ABBV-011.
• Serum Clearance (CL) of ABBV-011 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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).
• Clinical Benefit Rate (CBR) [ Time Frame: 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).
• Duration of Response (DOR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: August 17, 2018)

• Maximum Serum Concentration (Cmax) of SC-011 [ Time Frame: Up to approximately 15 weeks after first dose of study drug ]
  Maximum Serum Concentration (Cmax) of SC-011
• AUCinf of SC-011 [ Time Frame: Up to approximately 15 weeks after first dose of study drug ]
  Area under the serum concentration-time curve within a dosing interval of SC-011
• Overall Response Rate (ORR) [ Time Frame: Up to approximately 15 weeks after first dose of study drug ]
  ORR is defined as the proportion of subjects with confirmed complete response (CR) or partial response (PR) (CR+PR).
• Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 4 years ]
  Clinical benefit rate (CBR) is defined as the proportion of subjects with best overall response (confirmed or unconfirmed) of CR, PR or stable disease (SD).
• Progression-Free Survival (PFS) [ Time Frame: Up to approximately 4 years ]
  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.
• Duration of Objective Response (DOR) [ Time Frame: Up to approximately 4 years ]
  DOR is defined as the time from the subject's initial objective response (CR or PR) to PD or death due to any cause, whichever occurs first.
• Duration of Clinical Benefit (DOCB) [ Time Frame: Up to approximately 4 years ]
  DOCB is defined as the time from the subject's initial observation of clinical benefit (CR or PR or SD) to PD or death due to any cause, whichever occurs first.
• Overall Survival (OS) [ Time Frame: Up to approximately 4 years ]
  OS is defined as the time from the subject's first dose date to death due to any cause.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small Cell Lung Cancer

Intervention

• Drug: ABBV-011
  Intravenous
  Other Name: SC-011
• Drug: Budigalimab
  Intravenous
  Other Name: ABBV-181

Study Arms

• Experimental: Part A: ABBV-011 Dose Escalation
  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.
  Intervention: Drug: ABBV-011
• Experimental: Part B: ABBV-011 Dose Expansion
  ABBV-011 via intravenous administration at dose regimen(s) that will not exceed the maximum tolerated dose determined in Part A.
  Intervention: Drug: ABBV-011
• Experimental: Part C: ABBV-011 + Budigalimab Escalation and Expansion
  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.
  Interventions:

  • Drug: ABBV-011
  • Drug: Budigalimab
• Experimental: Part D: ABBV-011 Dose Evaluation for Japan
  ABBV-011 via intravenous administration will be administered every 3 weeks (Q3wk), on Day 1 of each 21-day cycle or alternate dosing regimens.
  Intervention: Drug: ABBV-011

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 15, 2023): 132
• Original Estimated Enrollment (submitted: August 17, 2018): 188
• Actual Study Completion Date: January 25, 2024
• Actual Primary Completion Date: January 25, 2024 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan, Korea, Republic of, Taiwan, United States

Administrative Information

• NCT Number: NCT03639194
• Other Study ID Numbers: M17-327
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: February 2024