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

NCT05029882 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: M21-4042023-509335-60-00
• Study Type: interventional
• Target: 520
• Locations: 10 countries
• Sites: 82

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

Keywords

Non-Small Cell Lung Cancer; ABBV-400; Advanced Solid Tumors; Gastroesophageal Adenocarcinoma; Colorectal Cancer; MET Amplification; MET Mutation; Trifluridine/Tipiracil; TAS-102; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• 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 48 Months

Secondary Outcomes (4)

• Duration of Response (DOR) for Participants with Confirmed CR/PR per RECIST v1.1

  Up to 48 Months

• PFS per RECIST v1.1

  Up to 48 Months

• Overall survival (OS)

  Up to 48 Months

• Parts 1-6: ORR per Independent Central Review (ICR) in Participants with MET Amplification

  Up to 48 Months

Study Arms (12)

Part 1 (Monotherapy Dose Escalation)

EXPERIMENTAL

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

Drug: ABBV-400

Part 2i (wtEGFR Non-Small Cell Lung Cancer [NSCLC])

EXPERIMENTAL

Participants with non-squamous wtEGFR NSCLC will receive ABBV-400 at the Recommended Phase 2 dose (RP2D).

Drug: ABBV-400

Part 2ii (mutEGFR NSCLC)

EXPERIMENTAL

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

Drug: ABBV-400

Part 2iii (Squamous NSCLC)

EXPERIMENTAL

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

Drug: ABBV-400

Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct

EXPERIMENTAL

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

Drug: ABBV-400

Part 4 (Colorectal Cancer)

EXPERIMENTAL

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

Drug: ABBV-400

Part 5 (MET Amplification)

EXPERIMENTAL

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

Part 6 (MET Mutation)

EXPERIMENTAL

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

Drug: ABBV-400

Part 7a (Combination Dose Escalation)

EXPERIMENTAL

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

Drug: ABBV-400; Drug: Bevacizumab

Part 7bi (Combination Dose Optimization Low Dose)

EXPERIMENTAL

Participants with CRC will receive the low dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.

Drug: ABBV-400; Drug: Bevacizumab

Part 7bii (Combination Dose Optimization High Dose)

EXPERIMENTAL

Participants with CRC will receive the high dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.

Drug: ABBV-400; Drug: Bevacizumab

Part 7biii (Combination Comparator)

EXPERIMENTAL

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

Drug: Trifluridine/Tipiracil; Drug: Bevacizumab

Interventions

ABBV-400 DRUG

Intravenous (IV) Infusion

Part 1 (Monotherapy Dose Escalation); Part 2i (wtEGFR Non-Small Cell Lung Cancer [NSCLC]); Part 2ii (mutEGFR NSCLC); Part 2iii (Squamous NSCLC); Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct; Part 4 (Colorectal Cancer); Part 5 (MET Amplification); Part 6 (MET Mutation); Part 7a (Combination Dose Escalation); Part 7bi (Combination Dose Optimization Low Dose); Part 7bii (Combination Dose Optimization High Dose)

Trifluridine/Tipiracil DRUG

Oral Tablet

Also known as: TAS-102

Part 7biii (Combination Comparator)

Bevacizumab DRUG

IV Infusion

Part 7a (Combination Dose Escalation); Part 7bi (Combination Dose Optimization Low Dose); Part 7bii (Combination Dose Optimization High Dose); Part 7biii (Combination Comparator)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (82)

University of California, Los Angeles /ID# 243841

Los Angeles, California, 90095, United States

Location

University Of Colorado Denver /ID# 231574

Aurora, Colorado, 80045-2530, United States

Location

Yale School of Medicine /ID# 248418

New Haven, Connecticut, 06519, United States

Location

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

Chicago, Illinois, 60607, United States

Location

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

Fort Wayne, Indiana, 46825, United States

Location

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

Indianapolis, Indiana, 46202-5112, United States

Location

Community Health Network, Inc. /ID# 245331

Indianapolis, Indiana, 46250-2042, United States

Location

Comprehensive Cancer Centers of Nevada /ID# 242930

Henderson, Louisiana, 89052, United States

Location

START Midwest /ID# 231551

Grand Rapids, Michigan, 49546-7062, United States

Location

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

New York, New York, 10065-6007, United States

Location

Duke Cancer Institute /ID# 247236

Durham, North Carolina, 27710, United States

Location

Carolina BioOncology Institute /ID# 231541

Huntersville, North Carolina, 28078, United States

Location

Duplicate_Gabrail Cancer Center Research /ID# 248419

Canton, Ohio, 44718, United States

Location

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

Houston, Texas, 77030-4000, United States

Location

Oncology Consultants /ID# 267347

Houston, Texas, 77030, United States

Location

NEXT Oncology /ID# 231578

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists - Fairfax /ID# 231575

Fairfax, Virginia, 22031, United States

Location

Northwest Medical Specialties Tacoma /ID# 267339

Tacoma, Washington, 98405, United States

Location

Mater Misericordiae Limited /ID# 249995

South Brisbane, Queensland, 4101, Australia

Location

Austin Health /ID# 247667

Heidelberg, Victoria, 3084, Australia

Location

Institut Bergonie /ID# 248028

Bordeaux, Gironde, 33000, France

Location

CHU Nantes - Hopital Laennec /ID# 244723

Saint-Herblain, Loire-Atlantique, 44800, France

Location

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

Saint-Herblain, Loire-Atlantique, 44805, France

Location

Centre Antoine-Lacassagne /ID# 231730

Nice, Provence-Alpes-Côte d'Azur Region, 06189, France

Location

Centre Leon Berard /ID# 250987

Lyon, Rhone, 69373, France

Location

Institut Gustave Roussy /ID# 246824

Villejuif, Val-de-Marne, 94805, France

Location

Centre Georges François Leclerc /ID# 244450

Dijon, 21079, France

Location

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

Paris, 75015, France

Location

Meir Medical Center /ID# 244179

Kfar Saba, Central District, 4428164, Israel

Location

Hadassah Medical Center /ID# 243821

Jerusalem, Jerusalem, 91120, Israel

Location

The Chaim Sheba Medical Center /ID# 231217

Ramat Gan, Tel Aviv, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center /ID# 245271

Tel Aviv, Tel Aviv, 6423906, Israel

Location

Rambam Health Care Campus /ID# 231218

Haifa, 3109601, Israel

Location

Rabin Medical Center /ID# 243363

Petah Tikva, 4941492, Israel

Location

NHO Nagoya Medical Center /ID# 250286

Nagoya, Aichi-ken, 460-0001, Japan

Location

Aichi Cancer Center Hospital /ID# 250284

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East /ID# 232008

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Yokohama Municipal Citizen's Hospital /ID# 248842

Yokohama, Kanagawa, 221-0855, Japan

Location

Kyoto University Hospital /ID# 250291

Kyoto, Kyoto, 606-8507, Japan

Location

Niigata University Medical & Dental Hospital /ID# 250952

Niigata, Niigata, 951-8520, Japan

Location

National Cancer Center Hospital /ID# 232007

Chuo-ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital Of JFCR /ID# 248447

Koto-ku, Tokyo, 135-8550, Japan

Location

Wakayama Medical University Hospital /ID# 250283

Wakayama, Wakayama, 641-8510, Japan

Location

Nagasaki University Hospital /ID# 250290

Nagasaki, 852-8501, Japan

Location

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

Poznan, Greater Poland Voivodeship, 60-693, Poland

Location

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

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

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

Przemyśl, Podkarpackie Voivodeship, 37-700, Poland

Location

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

Olsztyn, 10-357, Poland

Location

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

Rio Piedras, 00935, Puerto Rico

Location

Inje University Haeundae Hospital /ID# 244451

Busan, Busan Gwang Yeogsi, 48108, South Korea

Location

CHA Bundang Medical Center /ID# 247115

Seongnam, Gyeonggido, 13496, South Korea

Location

Gyeongsang National University Hospital /ID# 248420

Jinju, Gyeongsangnam-do, 52727, South Korea

Location

Chungbuk National University Hospital /ID# 245168

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Seoul National University Hospital /ID# 244667

Seoul, Seoul Teugbyeolsi, 03080, South Korea

Location

Kangbuk Samsung Hospital /ID# 248401

Seoul, Seoul Teugbyeolsi, 03181, South Korea

Location

Asan Medical Center /ID# 245215

Seoul, Seoul Teugbyeolsi, 05505, South Korea

Location

SMG-SNU Boramae Medical Center /ID# 248421

Seoul, Seoul Teugbyeolsi, 07061, South Korea

Location

Korea University Guro Hospital /ID# 244504

Seoul, Seoul Teugbyeolsi, 08308, South Korea

Location

Yonsei University Health System Severance Hospital /ID# 245218

Seoul, 03722, South Korea

Location

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

Santiago de Compostela, A Coruna, 15706, Spain

Location

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

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Fundacion Alcorcon /ID# 244505

Alcorcón, Madrid, 28922, Spain

Location

Clinica Universidad de Navarra - Pamplona /ID# 248816

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Vall de Hebron /ID# 249809

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona /ID# 245374

Barcelona, 08036, Spain

Location

Hospital Universitario de Jaen /ID# 249201

Jaén, 23007, Spain

Location

Hospital General Universitario Gregorio Maranon /ID# 245270

Madrid, 28007, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz /ID# 231464

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre /ID# 248417

Madrid, 28041, Spain

Location

Hospital Universitario HM Sanchinarro /ID# 244721

Madrid, 28050, Spain

Location

Hospital Universitario Virgen Macarena /ID# 245213

Seville, 41009, Spain

Location

Hospital Universitario Miguel Servet /ID# 244456

Zaragoza, 50009, Spain

Location

Duplicate_Kaohsiung Chang Gung Memorial Hospital /ID# 246449

Kaohsiung City, Kaohsiung, 833, Taiwan

Location

National Taiwan University Hospital /ID# 245731

Taipei City, Taipei, 100, Taiwan

Location

Changhua Christian Hospital /ID# 249150

Changhua City, Changhua County, 50006, Taiwan

Location

Cmuh /Id# 245729

Taichung, 40701, Taiwan

Location

National Cheng Kung University Hospital /ID# 245918

Tainan, 704, Taiwan

Location

Taipei Medical University Hospital /ID# 245732

Taipei, 11031, Taiwan

Location

Taipei Veterans General Hosp /ID# 250652

Taipei, 11217, Taiwan

Location

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

Taipei, 112, Taiwan

Location

Tri-Service General Hospital /ID# 245733

Taipei, 114, Taiwan

Location

Linkou Chang Gung Memorial Hospital /ID# 248716

Taoyuan, 333, Taiwan

Location

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Interventions

trifluridine tipiracil drug combination; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: September 1, 2021
• Study Start: October 13, 2021
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); KR (10); TW (10); JP (10); PL (4); ES (13); PR (1); FR (8); IL (6); US (18)