Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT05599984
• Recruitment Status: Recruiting
• First Posted: October 31, 2022
• Last Update Posted: May 6, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: October 28, 2022
• First Posted Date: October 31, 2022
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: December 5, 2022
• Estimated Primary Completion Date: October 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 28, 2022)

• Percentage of Participants With Adverse Events (AE) [ Time Frame: Up to Approximately 2 Years ]
  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
• Maximum Observed Serum/Plasma Concentration (Cmax) of ABBV-706 [ Time Frame: Up to Approximately 2 Years ]
  Maximum observed serum/plasma concentration of ABBV-706.
• Time to Cmax (Tmax) of ABBV-706 [ Time Frame: Up to Approximately 2 Years ]
  Time to Cmax of ABBV-706.
• Terminal Phase Elimination Half-Life (t1/2) of ABBV-706 [ Time Frame: Up to Approximately 2 Years ]
  Terminal phase elimination half-life (t1/2) of ABBV-706.
• Area Under the Serum/Plasma Concentration-Time Curve (AUC) of ABBV-706 [ Time Frame: Up to Approximately 2 Years ]
  Area under the serum/plasma concentration-time curve of ABBV-706.
• Antidrug Antibodies (ADAs) [ Time Frame: Up to Approximately 2 Years ]
  Incidence and concentration of anti-drug antibodies.
• Neutralizing Antibodies (nAbs) [ Time Frame: Up to Approximately 2 Years ]
  Incidence and concentration of neutralizing antibodies.
• Percentage of Participants with Objective Response, for Participants with Extracranial Solid Tumors [ Time Frame: Up to Approximately 2 Years ]
  Objective response is defined as participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 for for extracranial solid tumors per investigator assessment.
• Recommended Phase 2 Dose (RP2D) of ABBV-706 [ Time Frame: Up to Approximately 2 Years ]
  The RP2D will be determined using all available information, including, but not limited to, AEs, dose-limiting toxicities, pharmacokinetic parameters, clinical laboratory tests, and efficacy measures.
• Percentage of Participants with Objective Response for Participants with Central Nervous System (CNS) Tumors [ Time Frame: Up to Approximately 2 Years ]
  Objective response is as participants achieving a confirmed best overall response of CR and PR according to Response Assessment for Neuro-Oncology (RANO), version 1.1 for CNS tumors per investigator assessment.
• Duration of response (DOR) for Participants with Confirmed CR/PR [ Time Frame: Up to Approximately 2 Years ]
  For participants achieving a confirmed CR/PR, DOR is defined as the time from the initial response of CR/PR to disease progression or death of any cause, whichever occurs earlier.
• Percentage of Participants with Clinical Benefit [ Time Frame: Up to Approximately 2 Years ]
  Clinical benefit is defined as a participant achieving CR/PR, or Stable Disease (SD).
• Progression-Free Survival (PFS) [ Time Frame: Up to Approximately 2 Years ]
  PFS is defined as time from first study treatment to a documented disease progression, as determined by the investigator, or death due to any cause, whichever occurs earlier.
• Overall survival (OS) [ Time Frame: Up to Approximately 2 Years ]
  OS is defined as time from first study treatment to death due to any cause.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors
• Official Title: A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-706 as Monotherapy and in Combination With Budigalimab (ABBV-181), Carboplatin, or Cisplatin in Adult Subjects With Advanced Solid Tumors

Brief Summary

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-706 as a monotherapy and in combination with budigalimab, carboplatin, or cisplatin.

ABBV-706 is an investigational drug being developed for the treatment of small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors and high-grade neuroendocrine carcinomas (NECs). There are multiple treatment arms in this study. Participants will either receive ABBV-706 as a single agent or in combination with budigalimab (another investigational drug), carboplatin or cisplatin at different doses. Approximately 350 adult participants will be enrolled in the study across sites worldwide.

In part 1 (dose escalation), ABBV-706 will be intravenously infused in escalating doses as a monotherapy until the maximum tolerated dose (MTD) is determined in participants with SCLC, high-grade CNS tumors, and high-grade NECs. In part 2, multiple doses will be selected from Part 1 and SCLC participants will be assigned to one of these doses in a randomized fashion to determine the recommended Phase 2 dose. In Part 3a, participants with SCLC or NECs will receive ABBV-706 in combination with budigalimab intravenously every 3 weeks. In Part 3b participants with SCLC or NECs will receive ABBV-706 in combination with either carboplatin or cisplatin intravenously. In Part 4a, participants with CNS tumors will receive ABBV-706 intravenously at a dose determined from Part 1. In Part 4b, participants with NECs will receive ABBV-706 intravenously at a dose selected from Part 1. The estimated duration of the study is up to 3 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.

• 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: Advanced Solid Tumors

Intervention

• Drug: ABBV-706
  Intravenous (IV) Infusion
• Drug: Cisplatin
  Intravenous infusion
• Drug: Budigalimab
  IV Infusion
  Other Name: ABBV-181
• Drug: Carboplatin
  Intravenous infusion

Study Arms

• Experimental: Part 1: ABBV-706 Monotherapy Dose Escalation
  Participants will receive escalating doses of ABBV-706 until doses for optimization are determined, as part of an approximately 1 year treatment period.
  Intervention: Drug: ABBV-706
• Experimental: Part 2: ABBV-706 Monotherapy Dose Optimization and Expansion
  Participants with small cell lung cancer will receive varying doses of ABBV-706 in a randomized manner until the recommended phase 2 dose (RP2D) is achieved, as part of an approximately 1 year treatment period..
  Intervention: Drug: ABBV-706
• Experimental: Part 3a: ABBV-706 + Budigalimab
  Participants will receive ABBV-706 in combination with budigalimab, as part of an approximately 1 year treatment period.
  Interventions:

  • Drug: ABBV-706
  • Drug: Budigalimab
• Experimental: Part 3b: ABBV-706 + Platinum Chemotherapy
  Participants will receive ABBV-706 in combination with carboplatin or cisplatin, as part of an approximately 1 year treatment period.
  Interventions:

  • Drug: ABBV-706
  • Drug: Cisplatin
  • Drug: Carboplatin
• Experimental: Part 4a: ABBV-706 Monotherapy Dose Expansion CNS Tumors
  Participants with relapsed/refractory (R/R) central nervous system (CNS) tumors will receive ABBV-706 as a monotherapy at or below the maximum tolerated dose (MTD) maximum administered dose (MAD), as part of an approximately 1 year treatment period.
  Intervention: Drug: ABBV-706
• Experimental: Part 4b: ABBV-706 Monotherapy Dose Expansion NECs
  Participants with R/R neuroendocrine carcinomas (NECs) will receive IV Infused ABBV-706 as a monotherapy at or below the MTD/MAD, as part of an approximately 1 year treatment period.
  Intervention: Drug: ABBV-706

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 28, 2022): 350
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 17, 2027
• Estimated Primary Completion Date: October 15, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• The laboratory values criteria must be met within 7 days prior to the first dose of study drug as per the protocol.
• QT interval corrected for heart rate (QTc) <= 450 msec (males) or <= 470 msec (females) using Fridericia's correction, and an ejection fraction of >= 50% as measured by echocardiogram or multigated acquisition (MUGA) scan at Screening.
• Part 1 only: Advanced recurrent or refractory solid tumors with potential SEZ6 expression including small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors (glioblastoma [GBM], IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4), neuroendocrine prostate cancer (NEPC), high-grade poorly differentiated gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)s, large cell neuroendocrine carcinoma (LCNEC)s, SCLC transformed from epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), atypical lung carcinoids, and other high-grade poorly differentiated NECs, who have progressed on or after standard of care (SoC) therapy and with no curative therapy available. For SCLC, participants must have histologically or cytologically confirmed SCLC that is relapsed or refractory following at least 1 prior platinum-containing chemotherapy.
• Part 2 only: Histologically or cytologically confirmed SCLC that is relapsed or refractory (R/R) following at least 1 prior platinum-containing chemotherapy and with no curative therapy available. For the purposes of this study, a line of therapy is defined as >= 1 complete cycle of either a single agent or combination of drugs, including any planned sequential therapy of various regimens.
• Part 3a only: Participants with R/R SCLC following at least 1 prior platinum-containing chemotherapy or R/R poorly differentiated NECs, e.g., NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant Non-small cell lung cancer (NSCLC), atypical lung carcinoids, other high-grade poorly differentiated NECs.
• Part 3b only: Participants with R/R SCLC who have only progressed following a frontline regimen containing a platinum-based chemotherapy or R/R NECs, e.g., NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, other NECs.
• Part 4a only: Participants with R/R high-grade CNS tumors (GBM, IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4) who have progressed on SoC therapy and with no curative therapy options available.
• Part 4b only: Participants with R/R neuroendocrine tumors, including NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, and other high-grade poorly differentiated NECs, who have progressed on SoC therapy and with no curative therapy options available.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for participants with extracranial solid tumors or Response Assessment for Neuro-Oncology (RANO)for participants with primary high-grade CNS tumors (GBM, IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4).
• Primary CNS tumors within 12 weeks from radiation therapy should have unequivocal progression as documented by either tumor recurrence predominantly outside of radiation field on magnetic resonance imaging (MRI) or confirmed on tumor biopsy.
• Participants with brain metastases from an extracranial solid tumor are eligible if the brain metastases as outlined in the protocol.
• Fresh or archival tumor tissue available for submission, for retrospective SEZ6 expression analysis as outlined in the protocol.

Exclusion Criteria:

• History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or pneumonitis.
• History of idiopathic pulmonary fibrosis or organizing pneumonia.
• Prior treatment with an antibody drug conjugate that consists of a Top1 inhibitor payload.
• Part 2 only: Prior treatment with a SEZ6-targeted antibody drug conjugate.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Australia, Germany, Israel, Japan, Korea, Republic of, Spain, United States

Administrative Information

• NCT Number: NCT05599984
• Other Study ID Numbers: M23-385
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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: May 2024