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

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. 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. Approximately 460 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. In the 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 intravenous (IV) ABBV-400 monotherapy in expansion [Part 4], and participants MET amplification will receive intravenous (IV) ABBV-400 monotherapy in expansion [Part 5]. 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.

Official Title
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A Phase 1 First in Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-400 in Adult Subjects With Advanced Solid Tumors

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

Intervention / Treatment
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* Drug: ABBV-400


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic malignant solid tumor diagnosis (World Health Organization [WHO] criteria). Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. For Part 1 only - history of advanced solid tumor that has 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 - history of advanced non-squamous wtEGFR or mutEGFR or history of advanced 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 and squamous NSCLC (Parts 2i and 2iii). Platinum-based chemotherapy doublet and tyrosine kinase inhibitor(s) (TKI[s]) for non- squamous mutEGFR NSCLC (Part 2ii). Should 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 - history of advanced histopathologically or cytologically confirmed diagnosis of gastroesophageal adenocarcinoma/gastroesophagel junction adenocarcinoma (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. 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 treatment with Lonsurf or Regorafenib is also acceptable. 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. 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 pneumonitis. 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.

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 (Monotherapy Dose Escalation)<br>Participants with advanced solid tumors will receive escalating doses of ABBV-400. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 2i (wtEGFR Non-Small Cell Lung Cancer [NSCLC])<br>Participants with non-squamous wtEGFR NSCLC will receive ABBV-400 at the Recommended Phase 2 dose (RP2D). | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 2ii (mutEGFR NSCLC)<br>Participants with non-Squamous mutEGFR NSCLC will receive ABBV-400 at RP2D. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 2iii (Squamous NSCLC)<br>Participants with squamous NSCLC will receive ABBV-400 at RP2D. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junction Adenocarcinoma)<br>Participants with gastroesophageal adenocarcinoma will receive ABBV-400 at the RP2D. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 4 (Colorectal Cancer)<br>Participants with Colorectal Cancer will receive ABBV-400 at the RP2D and various dose levels for dose optimization. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|
| Experimental: Part 5 (MET Amplification)<br>Participants with mesenchymal-epithelial transition proto-oncogene (MET) amplification will receive ABBV-400 at the RP2D and various dose levels for dose optimization. | Drug: ABBV-400<br>* Intravenous (IV) Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | 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. | Up to Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) for Participants with Confirmed CR/PR per RECIST v1.1 | 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. | Up to 24 Months | 
| PFS per RECIST v1.1 | 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. | Up to 24 Months | 
| Overall survival (OS) | Overall survival (OS) is defined as time from first study treatment to death due to any cause. | Up to 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, ABBV-400, Advanced Solid Tumors, Gastroesophageal Adenocarcinoma, Colorectal Cancer, Gastroesophagel Junction Adenocarcinoma