A Study With ABBV-155 Alone and in Combination With Taxane Therapy in Adults With Relapsed and/or Refractory Solid Tumors

• ClinicalTrials.gov Identifier: NCT03595059
• Recruitment Status: Active, not recruiting
• First Posted: July 23, 2018
• Last Update Posted: May 18, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: July 12, 2018
• First Posted Date: July 23, 2018
• Last Update Posted Date: May 18, 2023
• Actual Study Start Date: July 13, 2018
• Estimated Primary Completion Date: November 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 21, 2020)

• MTD and/or RPTD of ABBV-155 [ Time Frame: Up to approximately 21 days after initial dose of study drug ]
  The Maximum Tolerated Dose (MTD) and/or the Recommended Phase Two Dose (RPTD) of ABBV-155 will be determined during the dose escalation phase (Part 1).
• Overall Response Rate (ORR) [ Time Frame: Up to approximately 2 to 6 months ]
  ORR is defined as the percentage of participants with documented best response partial response (PR) or better according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Original Primary Outcome Measures (submitted: July 12, 2018)

• MTD and/or RPTD of ABBV-155 [ Time Frame: Up to approximately 21 days after initial dose of study drug ]
  The Maximum Tolerated Dose (MTD) and/or the Recommended Phase Two Dose (RPTD) of ABBV-155 will be determined during the dose escalation phase (Part 1).
• Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 to 6 months ]
  ORR is defined as the percentage of participants with documented best response partial response (PR) or better according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Current Secondary Outcome Measures (submitted: February 16, 2021)

• Number of Participants with Adverse Events (AE) [ Time Frame: Up to approximately 12 months ]
  An AE is defined as any untoward medical occurrence in a subject or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
• Duration of Response (DOR) [ Time Frame: Up to approximately 12 months ]
  DOR is defined as the number of days from the date of first documented response (PR or better) to the date of the first documented disease progression (PD) or death due to disease, whichever occurs first.
• Rate of Complete Response (CR) [ Time Frame: Up to approximately 2 to 6 months ]
  CR is defined as the percentage of participants with documented best response CR according to RECIST version 1.1
• Progression-Free Survival (PFS) [ Time Frame: Up to approximately 12 months ]
  PFS is defined as the number of days from the date of first dose of study drug to the date of the first documented PD or death due to any cause, whichever occurs first.
• Overall Survival (OS) [ Time Frame: Up to approximately 12 months after last dose of study drug ]
  OS is defined as the number of days from the date of first study drug to the date of death due to any cause.
• Cmax of ABBV-155 [ Time Frame: Up to approximately 48 days ]
  Maximum plasma concentration (Cmax).
• Tmax of ABBV-155 [ Time Frame: Up to approximately 48 days ]
  Time to maximum plasma concentration (Tmax).
• Terminal Phase Elimination Rate constant of ABBV-155 [ Time Frame: Up to approximately 48 days ]
  Terminal phase elimination rate constant of ABBV-155
• AUCt of ABBV-155 [ Time Frame: Up to approximately 48 days ]
  Area under the plasma concentration versus time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt).
• AUCinf of ABBV-155 [ Time Frame: Up to approximately 48 days ]
  AUC from time 0 to infinite time (AUCinf).
• QTcF Change from Baseline [ Time Frame: Up to approximately 8 days ]
  QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level of ABBV-155 Monotherapy.
• t1/2 of ABBV-155 [ Time Frame: Up to approximately 48 days ]
  Terminal elimination half-life (t1/2).

Original Secondary Outcome Measures (submitted: July 12, 2018)

• Duration of Response (DOR) [ Time Frame: Up to approximately 12 months ]
  DOR is defined as the number of days from the date of first documented response (PR or better) to the date of the first documented disease progression (PD) or death due to disease, whichever occurs first.
• Rate of Complete Response (CR) [ Time Frame: Up to approximately 2 to 6 months ]
  CR is defined as the percentage of subjects with documented best response CR according to RECIST version 1.1
• Progression-Free Survival (PFS) [ Time Frame: Up to approximately 12 months ]
  PFS is defined as the number of days from the date of first dose of study drug to the date of the first documented PD or death due to any cause, whichever occurs first.
• Overall Survival (OS) [ Time Frame: Up to approximately 12 months after last dose of study drug ]
  OS is defined as the number of days from the date of first study drug to the date of death due to any cause.
• Cmax [ Time Frame: Up to approximately 48 days ]
  Maximum plasma concentration (Cmax).
• Tmax of ABBV-155 [ Time Frame: Up to approximately 48 days ]
  Time to maximum plasma concentration (Tmax).
• Terminal Phase Elimination Rate constant of ABBV-155 [ Time Frame: Up to approximately 48 days ]
  Terminal phase elimination rate constant of ABBV-155
• AUCt [ Time Frame: Up to approximately 48 days ]
  Area under the plasma concentration versus time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt).
• AUC∞ [ Time Frame: Up to approximately 48 days ]
  AUC from time 0 to infinite time (AUC∞).
• QTcF Change from Baseline [ Time Frame: Up to approximately 8 days ]
  QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level of ABBV-155 Monotherapy.
• t1/2 [ Time Frame: Up to approximately 48 days ]
  Terminal elimination half-life (t1/2).

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

Descriptive Information

• Brief Title: A Study With ABBV-155 Alone and in Combination With Taxane Therapy in Adults With Relapsed and/or Refractory Solid Tumors
• Official Title: A Phase 1 First-in-Human Study With ABBV-155 Alone and in Combination With Taxane Therapy in Adults With Relapsed and/or Refractory Solid Tumors

Brief Summary

An open-label, dose-escalation (Part 1), dose-expansion (Part 2) study to assess the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-155 alone and in combination with paclitaxel or docetaxel.

In Part 1 (dose escalation), participants will receive escalating doses of ABBV-155 monotherapy (Part 1a) or ABBV-155 in combination with paclitaxel or docetaxel (Part 1b).

In Part 2 (dose expansion), participants will receive ABBV-155 monotherapy or in combination therapy. The ABBV-155 monotherapy cohort will enroll participants with relapsed or refractory (R/R) small cell lung cancer (SCLC) (Part 2a); the ABBV-155 plus a taxane (paclitaxel or docetaxel) combination cohort will enroll participants with R/R non-small cell lung cancer (NSCLC) and breast cancer (Part 2b).

• Detailed Description: The Escalation cohorts (Part 1) have been completed. The expansion cohorts (Part 2) are open to enrollment.
• 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-155
  Intravenous (IV) Infusion
• Drug: Paclitaxel
  Intravenous (IV) Infusion
• Drug: Docetaxel
  Intravenous (IV) Infusion

Study Arms

• Experimental: Escalation 1a: ABBV-155
  Participants will be administered ABBV-155 (various doses).
  Intervention: Drug: ABBV-155
• Experimental: Escalation 1b: ABBV-155 + paclitaxel or docetaxel
  Participants will be administered ABBV-155 (various doses) in combination with paclitaxel or docetaxel .
  Interventions:

  • Drug: ABBV-155
  • Drug: Paclitaxel
  • Drug: Docetaxel
• Experimental: Expansion 2a: ABBV-155 in SCLC
  Description: Participants with small cell lung cancer (SCLC) will administer ABBV-155 (at the recommended Phase 2 dose).
  Intervention: Drug: ABBV-155
• Experimental: Expansion 2b: ABBV-155 + paclitaxel in Breast Cancer
  Participants with breast cancer will be administered ABBV-155 (at the recommended Phase 2 dose identified for combination with paclitaxel in part 1b) in combination with paclitaxel.
  Interventions:

  • Drug: ABBV-155
  • Drug: Paclitaxel
• Experimental: Expansion 2b: ABBV-155 + docetaxel in NSCLC
  Participants with non-small cell lung cancer (NSCLC) will be administered ABBV-155 (at or near the recommended Phase 2 dose identified for combination with paclitaxel in part 1b) in combination with docetaxel.
  Interventions:

  • Drug: ABBV-155
  • Drug: Docetaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 15, 2023): 169
• Original Estimated Enrollment (submitted: July 12, 2018): 125
• Estimated Study Completion Date: November 1, 2023
• Estimated Primary Completion Date: November 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Has a histologic or cytologic diagnosis of a malignant solid tumor.
• Participants enrolled in Part 2a (monotherapy, dose expansion) must have small cell lung cancer (SCLC) diagnosis; participants enrolled to Part 2b (combination therapy, dose expansion) must have either NSCLC or HR-positive/HER2-negative breast cancer.
• Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
• Failure of at least 1 prior systemic chemotherapy including all available standard therapies for participants in the dose-escalation phase (Parts 1a and 1b) including the safety lead-in phase (Japan only).

• All participants with breast cancer for subjects in the dose-expansion phase (Part 2b only) must have the following:

  • Locally advanced or metastatic HR-positive/HER2-negative breast cancer after failing cyclin-dependent kinase (CDK)4/6 inhibitor-based therapy.
  • HR-positivity and HER-2-negativity should be confirmed based on American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria.
• All participants with non-small cell lung cancer (NSCLC) for participants in the dose-expansion phase (Part 2b only) must have R/R NSCLC after at least 1 line of therapy. Participants with activating mutations in EGFR, ALK/ROS1, BRAF genes, or with positive expression of PD-L1 must have been treated with the appropriate targeted therapies.
• All participants with SCLC in the dose-expansion phase (Part 2a only) must have R/R SCLC from at least 1 line of therapy which includes a platinum-based therapy with or without an anti-PD-1/PD-L1 therapy.

• All participants with either breast cancer or NSCLC must have the following if exposed to prior taxane-based therapy:

  • No history of taxane allergy (Part 1b and Part 2b only).
  • Disease that has relapsed or progressed at least 2 months after most recent exposure to any taxane-based therapy.
• Available tumor tissue suitable for immunohistochemistry testing.
• Adequate kidney, liver, and hematologic laboratory values as described in the protocol.

Exclusion Criteria:

• Untreated brain or meningeal metastases (participants with a history of metastases may be eligible based on details described in the protocol).
• Grade 2 or higher peripheral neuropathy (only applies to participants who would receive taxane therapy).
• Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
• Known active infection of hepatitis B, hepatitis C, or human immunodeficiency virus with exceptions as described in the protocol.
• Recent history (within 6 months) of congestive heart failure (defined in the protocol), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological or surgical intervention, pericardial effusion, or pericarditis.
• Any history of hypersensitivity to any ingredients of ABBV-155 will be excluded. For combination therapy only (Parts 1b and 2b), no history of serious allergic reaction to any taxane or any ingredients used in taxane formulation (e.g., cremaphor).

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: Australia, Canada, Israel, Japan, Korea, Republic of, Netherlands, Puerto Rico, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT03595059
• Other Study ID Numbers: M16-573
• 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: March 2023