Study of Intravenous (IV) ABBV-637 Alone or in Combination With IV Docetaxel/Osimertinib to Assess Adverse Events and Change in Disease Activity in Adult Participants With Relapsed/Refractory (R/R) Solid Tumors

Study Overview
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Brief Summary
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Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to evaluate the safety and efficacy (how well the study drug works against the disease) of ABBV-637 alone or in combination with docetaxel/osimertinib in participants with solid tumors (NSCLC). Adverse events and change in disease activity will be assessed. ABBV-637 is an investigational drug being developed for the treatment of solid tumors. Study consists of 3 parts - monotherapy dose escalation (Part 1), combination dose escalation and expansion (Parts 2a and 2b) with docetaxel and combination dose escalation and expansion (Parts 3a and 3b) with osimertinib. Approximately 109 adult participants with relapsed/refractory (R/R) solid tumors will be enrolled in approximately 30 sites across the world. In Part 1, participants with solid tumors will receive intravenous (IV) ABBV-637 in 28-day cycles. In Part 2a and 2b, participants will receive IV ABBV-637 in combination with IV docetaxel in 28-day cycles. In Part 3a and 3b, participants will receive intravenous (IV) ABBV-637 in combination with daily oral tablets of osimertinib in 28-day cycle. 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. Treatment effects will be monitored by medical assessments, blood tests, side effect reporting, and questionnaires.

Official Title
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A Phase 1 First In Human Study Evaluating Safety And Efficacy Of ABBV-637 As Either Monotherapy Or In Combination In Adult Subjects With Relapsed And Refractory Solid Tumors

Conditions
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Advanced Solid Tumors Cancer, Non Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: ABBV-637
* Drug: Docetaxel
* Drug: Osimertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic solid tumor diagnosis (Part 1). For Part 2 docetaxel combination therapy: EGFR WT expressing relapsed/refractory (R/R) non-small cell lung cancer (NSCLC) participants. For Part 3 osimertinib combination therapy: mutEGFR-expressing RR NSCLC participants. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. For Part 1 only - history of R/R disease that has progressed on all standard of care therapy. For Part 2 only - history of RR NSCLC that has progressed after treatment with platinum-based chemotherapy regimen and either immune checkpoint inhibitor or targeted therapy and may not have been treated with prior single agent chemotherapy. For Part 3 only - history of RR NSCLC that has progressed on osimertinib Meet the laboratory values as described in the protocol. Exclusion Criteria: History (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological or surgical intervention, pericardial effusion, or pericarditis. Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia. For Part 3 only: History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or pneumonitis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: ABBV-637 Monotherapy<br>Participants will receive escalating doses of ABBV-637 in 28-day cycles. | Drug: ABBV-637<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 2a: ABBV-637 + Docetaxel<br>Participants will receive escalating doses of ABBV-637 in combination with docetaxel in 28-day cycles. | Drug: ABBV-637<br>* Intravenous (IV) Infusion<br>Drug: Docetaxel<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 2b: ABBV-637 + Docetaxel<br>Participants will receive ABBV-637 at dose determined in Part 2a in combination with docetaxel in 28-day cycles. | Drug: ABBV-637<br>* Intravenous (IV) Infusion<br>Drug: Docetaxel<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 3a: ABBV-637 + Osimertinib<br>Participants will receive escalating doses of ABBV-637 in combination with osimertinib in 28-day cycles. | Drug: ABBV-637<br>* Intravenous (IV) Infusion<br>Drug: Osimertinib<br>* Oral Tablets<br>|
| Experimental: Part 3b: ABBV-637 + Osimertinib<br>Participants will receive ABBV-637 at dose determined in Part 3a in combination with osimertinib in 28-day cycles. | Drug: ABBV-637<br>* Intravenous (IV) Infusion<br>Drug: Osimertinib<br>* Oral Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events (AEs) | 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 drug. 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. | Up to approximately 3 years | 
| Percentage of Participants With Objective Response Rate (ORR) (Part 2 & 3) | ORR is defined as the percentage of participants with a confirmed response (CR) or partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response Rate (ORR) (Part 1) | ORR is defined as the percentage of participants with a confirmed response (CR) or partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Up to approximately 3 years | 
| Duration of Response (DOR) for ABBV-637 Administered as Monotherapy (Part 1) | DOR is defined as the time from the initial response of CR/PR per investigator review according to RECIST version 1.1 criteria to the first occurrence of radiographic disease progression, clinical progression or death from any cause whichever occurs first. | Up to approximately 12 months | 
| Duration of Response (DOR) for ABBV-637 in Combination With Docetaxel and Osimertinib (Part 2 & 3) | DOR is defined as the time from the initial response of CR/PR per investigator review according to RECIST version 1.1 criteria to the first occurrence of radiographic disease progression, clinical progression or death from any cause whichever occurs first. | Up to approximately 20 months | 
| Progression-Free Survival (PFS) for ABBV-637 in Combination With Docetaxel and Osimertinib (Part 2 & 3) | PFS is defined as the time from the first dose of any study drug to a documented radiographic disease progression according to RECIST version 1.1 as determined by the investigator, clinical progression or death from any cause, whichever occurs earlier. | Up to approximately 20 months | 
| Overall Survival (OS) for ABBV-637 in Combination With Docetaxel and Osimertinib (Part 2 & 3) | OS is defined as the time from the first dose of any study drug until death from any cause. | Up to approximately 12 months after last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumors Cancer, Non Small Cell Lung Cancer, NSCLC, Cancer, ABBV-637, Docetaxel, Osimertinib