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

NCT ID: NCT05029882

Last Updated: 2025-10-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 520 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-13
• Study Completion Date: 2027-11-30

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 (Monotherapy Dose Escalation)

Participants with advanced solid tumors will receive escalating doses of ABBV-400.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

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).

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Part 2ii (mutEGFR NSCLC)

Participants with non-Squamous mutEGFR NSCLC will receive ABBV-400 at RP2D.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Part 2iii (Squamous NSCLC)

Participants with squamous NSCLC will receive ABBV-400 at RP2D.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct

Participants with gastroesophageal adenocarcinoma will receive ABBV-400 at the RP2D.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Part 4 (Colorectal Cancer)

Participants with Colorectal Cancer (CRC) will receive ABBV-400 at the RP2D and various dose levels for dose optimization.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

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.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Part 6 (MET Mutation)

Participants with MET mutation will receive ABBV-400 at the RP2D and various dose levels for dose optimization.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Part 7a (Combination Dose Escalation)

Participants with CRC will receive escalating doses of ABBV-400 in combination with bevacizumab.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Bevacizumab

Intervention Type: DRUG

IV Infusion

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.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Bevacizumab

Intervention Type: DRUG

IV Infusion

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.

Group Type: EXPERIMENTAL

ABBV-400

Intervention Type: DRUG

Intravenous (IV) Infusion

Bevacizumab

Intervention Type: DRUG

IV Infusion

Part 7biii (Combination Comparator)

Participants with CRC will receive trifluridine/tipiracil (TAS-102) in combination with bevacizumab.

Group Type: EXPERIMENTAL

Trifluridine/Tipiracil

Intervention Type: DRUG

Oral Tablet

Bevacizumab

Intervention Type: DRUG

IV Infusion

Interventions

ABBV-400

Intravenous (IV) Infusion

Intervention Type: DRUG

Trifluridine/Tipiracil

Oral Tablet

Intervention Type: DRUG

Bevacizumab

IV Infusion

Intervention Type: DRUG

Other Intervention Names

TAS-102

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

University of California, Los Angeles /ID# 243841

Los Angeles, California, United States

University Of Colorado Denver /ID# 231574

Aurora, Colorado, United States

Yale School of Medicine /ID# 248418

New Haven, Connecticut, United States

University of Illinois Hospital and Health Sciences System /ID# 251386

Chicago, Illinois, United States

Fort Wayne Medical Oncology and Hematology - Fort Wayne - East Dupont Road /ID# 267338

Fort Wayne, Indiana, United States

Indiana University Melvin and Bren Simon Cancer Center /ID# 245133

Indianapolis, Indiana, United States

Community Health Network, Inc. /ID# 245331

Indianapolis, Indiana, United States

Comprehensive Cancer Centers of Nevada /ID# 242930

Henderson, Louisiana, United States

START Midwest /ID# 231551

Grand Rapids, Michigan, United States

Memorial Sloan Kettering Cancer Center-Koch Center /ID# 250668

New York, New York, United States

Duke Cancer Institute /ID# 247236

Durham, North Carolina, United States

Carolina BioOncology Institute /ID# 231541

Huntersville, North Carolina, United States

Duplicate_Gabrail Cancer Center Research /ID# 248419

Canton, Ohio, United States

MD Anderson Cancer Center at Texas Medical Center /ID# 248656

Houston, Texas, United States

Oncology Consultants /ID# 267347

Houston, Texas, United States

NEXT Oncology /ID# 231578

San Antonio, Texas, United States

Virginia Cancer Specialists - Fairfax /ID# 231575

Fairfax, Virginia, United States

Northwest Medical Specialties Tacoma /ID# 267339

Tacoma, Washington, United States

Mater Misericordiae Limited /ID# 249995

South Brisbane, Queensland, Australia

Austin Health /ID# 247667

Heidelberg, Victoria, Australia

Institut Bergonie /ID# 248028

Bordeaux, Gironde, France

CHU Nantes - Hopital Laennec /ID# 244723

Saint-Herblain, Loire-Atlantique, France

Institut de Cancérologie de l'Ouest René Gauducheau /ID# 248399

Saint-Herblain, Loire-Atlantique, France

Centre Antoine-Lacassagne /ID# 231730

Nice, Provence-Alpes-Côte d'Azur Region, France

Centre Leon Berard /ID# 250987

Lyon, Rhone, France

Institut Gustave Roussy /ID# 246824

Villejuif, Val-de-Marne, France

Centre Georges François Leclerc /ID# 244450

Dijon, , France

AP-HP - Hopital Européen Georges Pompidou /ID# 250481

Paris, , France

Meir Medical Center /ID# 244179

Kfar Saba, Central District, Israel

Hadassah Medical Center /ID# 243821

Jerusalem, Jerusalem, Israel

The Chaim Sheba Medical Center /ID# 231217

Ramat Gan, Tel Aviv, Israel

Tel Aviv Sourasky Medical Center /ID# 245271

Tel Aviv, Tel Aviv, Israel

Rambam Health Care Campus /ID# 231218

Haifa, , Israel

Rabin Medical Center /ID# 243363

Petah Tikva, , Israel

NHO Nagoya Medical Center /ID# 250286

Nagoya, Aichi-ken, Japan

Aichi Cancer Center Hospital /ID# 250284

Nagoya, Aichi-ken, Japan

National Cancer Center Hospital East /ID# 232008

Kashiwa-shi, Chiba, Japan

Yokohama Municipal Citizen's Hospital /ID# 248842

Yokohama, Kanagawa, Japan

Kyoto University Hospital /ID# 250291

Kyoto, Kyoto, Japan

Niigata University Medical & Dental Hospital /ID# 250952

Niigata, Niigata, Japan

National Cancer Center Hospital /ID# 232007

Chuo-ku, Tokyo, Japan

The Cancer Institute Hospital Of JFCR /ID# 248447

Koto-ku, Tokyo, Japan

Wakayama Medical University Hospital /ID# 250283

Wakayama, Wakayama, Japan

Nagasaki University Hospital /ID# 250290

Nagasaki, , Japan

Med Polonia Sp. z o. o. /ID# 250799

Poznan, Greater Poland Voivodeship, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 246569

Warsaw, Masovian Voivodeship, Poland

Wojewodzki Szpital im. Sw. Ojca Pio /ID# 251846

Przemyśl, Podkarpackie Voivodeship, Poland

Samodzielny Publiczny Zespó? Gru?licy i Chorób P?uc w Olsztynie /ID# 250466

Olsztyn, , Poland

Pan American Center for Oncology Trials, LLC /ID# 231580

Rio Piedras, , Puerto Rico

Inje University Haeundae Hospital /ID# 244451

Busan, Busan Gwang Yeogsi, South Korea

CHA Bundang Medical Center /ID# 247115

Seongnam, Gyeonggido, South Korea

Gyeongsang National University Hospital /ID# 248420

Jinju, Gyeongsangnam-do, South Korea

Chungbuk National University Hospital /ID# 245168

Cheongju-si, North Chungcheong, South Korea

Seoul National University Hospital /ID# 244667

Seoul, Seoul Teugbyeolsi, South Korea

Kangbuk Samsung Hospital /ID# 248401

Seoul, Seoul Teugbyeolsi, South Korea

Asan Medical Center /ID# 245215

Seoul, Seoul Teugbyeolsi, South Korea

SMG-SNU Boramae Medical Center /ID# 248421

Seoul, Seoul Teugbyeolsi, South Korea

Korea University Guro Hospital /ID# 244504

Seoul, Seoul Teugbyeolsi, South Korea

Yonsei University Health System Severance Hospital /ID# 245218

Seoul, , South Korea

Complejo Hospitalario Universitario de Santiago (CHUS) /ID# 245378

Santiago de Compostela, A Coruna, Spain

Instituto Catalan de Oncologia (ICO) Badalona /ID# 245379

Badalona, Barcelona, Spain

Hospital Universitario Fundacion Alcorcon /ID# 244505

Alcorcón, Madrid, Spain

Clinica Universidad de Navarra - Pamplona /ID# 248816

Pamplona, Navarre, Spain

Hospital Universitario Vall de Hebron /ID# 249809

Barcelona, , Spain

Hospital Clinic de Barcelona /ID# 245374

Barcelona, , Spain

Hospital Universitario de Jaen /ID# 249201

Jaén, , Spain

Hospital General Universitario Gregorio Maranon /ID# 245270

Madrid, , Spain

Hospital Universitario Fundacion Jimenez Diaz /ID# 231464

Madrid, , Spain

Hospital Universitario 12 de Octubre /ID# 248417

Madrid, , Spain

Hospital Universitario HM Sanchinarro /ID# 244721

Madrid, , Spain

Hospital Universitario Virgen Macarena /ID# 245213

Seville, , Spain

Hospital Universitario Miguel Servet /ID# 244456

Zaragoza, , Spain

Duplicate_Kaohsiung Chang Gung Memorial Hospital /ID# 246449

Kaohsiung City, Kaohsiung, Taiwan

National Taiwan University Hospital /ID# 245731

Taipei City, Taipei, Taiwan

Changhua Christian Hospital /ID# 249150

Changhua City, Changhua County, , Taiwan

Cmuh /Id# 245729

Taichung, , Taiwan

National Cheng Kung University Hospital /ID# 245918

Tainan City, , Taiwan

Taipei Medical University Hospital /ID# 245732

Taipei, , Taiwan

Taipei Veterans General Hosp /ID# 250652

Taipei, , Taiwan

Koo Foundation Sun Yat-Sen Cancer Center /ID# 245917

Taipei, , Taiwan

Tri-Service General Hospital /ID# 245733

Taipei, , Taiwan

Linkou Chang Gung Memorial Hospital /ID# 248716

Taoyuan, , Taiwan

Countries

United States; Australia; France; Israel; Japan; Poland; Puerto Rico; South Korea; Spain; Taiwan

Related Links

https://www.abbvieclinicaltrials.com/study/?id=M21-404

Related Info

Other Identifiers

2023-509335-60-00

Identifier Type: OTHER

Identifier Source: secondary_id

M21-404

Identifier Type: -

Identifier Source: org_study_id