Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Advanced Solid Tumors Receiving Intravenous (IV) ABBV-400 as Monotherapy and in Combination With IV Bevacizumab

• ClinicalTrials.gov Identifier: NCT05029882
• Recruitment Status: Recruiting
• First Posted: September 1, 2021
• Last Update Posted: April 11, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: August 30, 2021
• First Posted Date: September 1, 2021
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: October 13, 2021
• Estimated Primary Completion Date: November 23, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 3, 2023)

Objective Response Rate (ORR) [ Time Frame: Up to Month 24 ]

ORR defined as percentage of participants with confirmed best overall response of Confirmed complete response (CR) and partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Original Primary Outcome Measures (submitted: August 30, 2021)

Change it to Objective Response Rate (ORR) [ Time Frame: Up to Month 24 ]

ORR defined as percentage of participants with confirmed best overall response of Confirmed complete response (CR) and partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Current Secondary Outcome Measures (submitted: August 30, 2021)

• Duration of Response (DOR) for Participants with Confirmed CR/PR per RECIST v1.1 [ Time Frame: Up to 24 Months ]
  DOR is defined for participants achieving a confirmed CR+PR as the time from the initial response of CR+PR per investigator review according to RECIST 1.1 criteria to disease progression or death of any cause, whichever occurs earlier.
• PFS per RECIST v1.1 [ Time Frame: Up to 24 Months ]
  Progression-free survival (PFS) is defined as time from first study treatment to a documented disease progression according to RECIST version 1.1, as determined by the investigator, or death due to any cause, whichever occurs earlier.
• Overall survival (OS) [ Time Frame: Up to 24 Months ]
  Overall survival (OS) is defined as time from first study treatment to death due to any cause.

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

Descriptive Information

• Brief Title: Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Advanced Solid Tumors Receiving Intravenous (IV) ABBV-400 as Monotherapy and in Combination With IV Bevacizumab
• Official Title: A Phase 1 First in Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-400 as Monotherapy and in Combination With Bevacizumab 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 adverse events and change in disease activity when ABBV-400 is given to adult participants to treat advanced solid tumors.

ABBV-400 is an investigational drug being developed for the treatment of advanced solid tumors. Study doctors put the participants in groups called treatment arms. The Recommended Phase 2 dose (RP2D) will be explored. Each treatment arm receives a different dose of ABBV-400. This study will include a dose escalation phase to determine the best dose of ABBV-400, followed by a dose expansion phase to confirm the dose and combination with bevacizumab. Approximately 500 adult participants with NSCLC, gastroesophageal adenocarcinoma/gastroesophagel junction adenocarcinoma (GEA) and colorectal cancer (CRC) or advanced solid tumors, will be enrolled in the study in approximately 7-10 sites in the Dose Escalation phase and 85-95 sites in the Dose Expansion phase worldwide.

Dose escalation arms, participants will receive intravenous (IV) escalating doses of ABBV-400 monotherapy. Dose expansion arms, participants in the following advanced solid tumor indications: non-squamous NSCLC with wildtype EGFR-expression (wtEGFR NSCLC) [Part 2i] or mutated EGFR-expression (mutEGFR NSCLC) [Part 2ii], squamous NSCLC [Part 2iii], GEA [Part 3] will receive intravenous (IV) ABBV-400 monotherapy, participants CRC will receive IV ABBV-400 monotherapy in expansion [Part 4], participants MET amplification will receive IV ABBV-400 monotherapy in expansion [Part 5], participants MET mutation will receive IV ABBV-400 monotherapy in expansion [Part 6], participants CRC safety lead in will receive escalating doses of IV ABBV-400 in combination with IV bevacizumab [Part 7a], and participants CRC dose optimization in will the low or high dose of IV ABBV-400 determined in Part 7a in combination with IV bevacizumab or oral trifluridine/tipiracil (TAS-102) tablets [Part 7b].

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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

• 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

• Non-Small Cell Lung Cancer
• Advanced Solid Tumors
• Gastroesophageal Adenocarcinoma
• Colorectal Cancer

Intervention

• Drug: ABBV-400
  Intravenous (IV) Infusion
• Drug: Trifluridine/Tipiracil
  Oral Tablet
  Other Name: TAS-102
• Drug: Bevacizumab
  IV Infusion

Study Arms

• Experimental: Part 1 (Monotherapy Dose Escalation)
  Participants with advanced solid tumors will receive escalating doses of ABBV-400.
  Intervention: Drug: ABBV-400
• Experimental: Part 2i (wtEGFR Non-Small Cell Lung Cancer [NSCLC])
  Participants with non-squamous wtEGFR NSCLC will receive ABBV-400 at the Recommended Phase 2 dose (RP2D).
  Intervention: Drug: ABBV-400
• Experimental: Part 2ii (mutEGFR NSCLC)
  Participants with non-Squamous mutEGFR NSCLC will receive ABBV-400 at RP2D.
  Intervention: Drug: ABBV-400
• Experimental: Part 2iii (Squamous NSCLC)
  Participants with squamous NSCLC will receive ABBV-400 at RP2D.
  Intervention: Drug: ABBV-400
• Experimental: Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct
  Participants with gastroesophageal adenocarcinoma will receive ABBV-400 at the RP2D.
  Intervention: Drug: ABBV-400
• Experimental: Part 4 (Colorectal Cancer)
  Participants with Colorectal Cancer (CRC) will receive ABBV-400 at the RP2D and various dose levels for dose optimization.
  Intervention: Drug: ABBV-400
• Experimental: Part 5 (MET Amplification)
  Participants with mesenchymal-epithelial transition proto-oncogene (MET) amplification will receive ABBV-400 at the RP2D and various dose levels for dose optimization.
  Intervention: Drug: ABBV-400
• Experimental: Part 6 (MET Mutation)
  Participants with MET mutation will receive ABBV-400 at the RP2D and various dose levels for dose optimization.
  Intervention: Drug: ABBV-400
• Experimental: Part 7a (Combination Dose Escalation)
  Participants with CRC will receive escalating doses of ABBV-400 in combination with bevacizumab.
  Interventions:

  • Drug: ABBV-400
  • Drug: Bevacizumab
• Experimental: Part 7bi (Combination Dose Optimization Low Dose)
  Participants with CRC will receive the low dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.
  Interventions:

  • Drug: ABBV-400
  • Drug: Bevacizumab
• Experimental: Part 7bii (Combination Dose Optimization High Dose)
  Participants with CRC will receive the high dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.
  Interventions:

  • Drug: ABBV-400
  • Drug: Bevacizumab
• Experimental: Part 7biii (Combination Comparator)
  Participants with CRC will receive trifluridine/tipiracil (TAS-102) in combination with bevacizumab.
  Interventions:

  • Drug: Trifluridine/Tipiracil
  • Drug: Bevacizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 23, 2024): 500
• Original Estimated Enrollment (submitted: August 30, 2021): 100
• Estimated Study Completion Date: November 23, 2025
• Estimated Primary Completion Date: November 23, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of malignant solid tumor (World Health Organization [WHO] criteria).
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• For Part 1 only - advanced solid tumors including (but not limited to) non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastroesophagel junction adenocarcinoma (GEA), colorectal cancer (CRC), and renal cell carcinoma (RCC), who have progressed on all standard of care therapy and are not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.

• For Part 2 only - advanced non-squamous squamous Non-Small Cell Lung Cancer (NSCLC) that have progressed after treatment with at least:

  • Platinum-based chemotherapy and an immune checkpoint inhibitor and/or appropriate targeted therapy for an actionable gene alteration, if applicable, for non-squamous wtEGFR NSCLC (Part 2i) and squamous NSCLC (Part 2iii).
  • Platinum-based chemotherapy doublet and tyrosine kinase inhibitor(s) (TKI[s]) for non- squamous mutEGFR NSCLC (Part 2ii).
  • Must have no more than 2 lines of prior cytotoxic chemotherapy excluding adjuvant therapy and must have advanced NSCLC that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.

• For Part 3 only - Participants with advanced GEA that has progressed after treatment with at least 1 prior cytotoxic chemotherapeutic regimen for locally advanced or metastatic disease and have not received more than 2 prior lines of cytotoxic chemotherapy regimens. Participants must have progressed on

  • If applicable, an immune checkpoint inhibitor.
  • If applicable, appropriate available therapies, including HER2-directed therapies.

Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible.

• For Part 4 only - Participants with history of advanced histopathologically or cytologically confirmed colorectal cancer (CRC) that does not harbor the BRAF V600E mutation and are not dMMR+/MSI-Hi with progression on:

  • A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine).
  • Oxaliplatin.
  • Irinotecan.
  • If applicable, anti-EGFR (including, but not limited to cetuximab or panitumumab).
  • If applicable, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, or aflibercept).
  • If applicable, targeted therapy
  • Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible. Prior trifluridine/tipiracil (TAS-102) or Regorafenib treated participants are eligible.
• For Part 5 only - participants with advanced histologically or cytologically confirmed solid tumors characterized by MET amplification who are not amenable to surgical resection and who have disease progression after at least one prior systemic therapy and/or who have no satisfactory alternative treatment options. Participants who are intolerant to standard treatment are eligible.

For Part 6 only - Participants with advanced histologically or cytologically confirmed solid tumors harboring MET mutations including: mutations in the tyrosine kinase domain, the juxtamembrane region and the extracellular domain (as locally determined by next-generation sequencing (NGS) or a validated qPCR on tissue), who are not amenable to surgical resection and who have disease progression after at least one prior systemic therapy and/or who have no satisfactory alternative treatment options.

• Intolerant to the standard treatment are eligible

• For Part 7 (CRC combination) only: Participants with history of advanced histopathologically or cytologically confirmed CRC that does not harbor the mutation and are not dMMR+/MSI-H with progression on:

  • A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine)
  • Oxaliplatin
  • Irinotecan
  • If applicable, anti-EGFR (including, but not limited to cetuximab or panitumumab)
  • If applicable, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, or aflibercept)
  • If applicable, targeted therapy Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible. Participants treated previously with TAS-102 or regorafenib are not eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Laboratory values meeting the criteria 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 on screening chest CT scan..
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
• History of clinically significant, intercurrent lung-specific illnesses, as noted in the protocol.
• For Part 7 only: Prior TAS-102 or regorafenib treated participants are not eligible.

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, France, Israel, Japan, Korea, Republic of, Poland, Puerto Rico, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT05029882
• Other Study ID Numbers: M21-404; 2023-509335-60-00 ( Other Identifier: EU CT )
• 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: April 2024