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

Colorectal Cancer Clinical Trial

Official title:

A Phase 1 First in Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-400 as Monotherapy and in Combination With Bevacizumab in Adult Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05029882
• Other study ID #: M21-404
• Secondary ID: 2023-509335-60-0
• Status: Recruiting
• Phase: Phase 1
• Start date: October 13, 2021
• Est. completion date: November 23, 2025

Study information

• Verified date: April 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: November 23, 2025
• Est. primary completion date: November 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Solid Tumors
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Gastroesophageal Adenocarcinoma
• Non-Small Cell Lung Cancer

Intervention

Drug:
• ABBV-400
Intravenous (IV) Infusion
• Trifluridine/Tipiracil
Oral Tablet
• Bevacizumab
IV Infusion

Locations

Country	Name	City	State
Australia	Austin Health /ID# 247667	Heidelberg	Victoria
Australia	Mater Misericordiae Limited /ID# 249995	South Brisbane	Queensland
France	Institut Bergonie /ID# 248028	Bordeaux	Gironde
France	Centre Georges François Leclerc /ID# 244450	Dijon
France	Centre Leon Berard /ID# 250987	Lyon CEDEX 08	Rhone
France	Centre Antoine Lacassagne - Nice /ID# 231730	Nice	Alpes-Maritimes
France	AP-HP - Hopital Européen Georges Pompidou /ID# 250481	Paris
France	CHU Nantes - Hopital Laennec /ID# 244723	Saint-Herblain
France	Institut de Cancérologie de l'Ouest René Gauducheau /ID# 248399	St Herblain CEDEX	Loire-Atlantique
France	Institut Gustave Roussy /ID# 246824	Villejuif Cedex	Val-de-Marne
Israel	Rabin Medical Center /ID# 243363	Haifa	H_efa
Israel	Rambam Health Care Campus /ID# 231218	Haifa	H_efa
Israel	Hadassah Medical Center /ID# 243821	Jerusalem	Yerushalayim
Israel	Meir Medical Center /ID# 244179	Kfar Saba	HaMerkaz
Israel	The Chaim Sheba Medical Center /ID# 231217	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 245271	Tel Aviv	Tel-Aviv
Japan	National Cancer Center Hospital /ID# 232007	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East /ID# 232008	Kashiwa-shi	Chiba
Japan	The Cancer Institute Hospital Of JFCR /ID# 248447	Koto-ku	Tokyo
Japan	Kyoto University Hospital /ID# 250291	Kyoto-shi	Kyoto
Japan	Nagasaki University Hospital /ID# 250290	Nagasaki-shi	Nagasaki
Japan	Aichi Cancer Center Hospital /ID# 250284	Nagoya-shi	Aichi
Japan	NHO Nagoya Medical Center /ID# 250286	Nagoya-shi	Aichi
Japan	Niigata University Medical & Dental Hospital /ID# 250952	Niigata-shi	Niigata
Japan	Wakayama Medical University Hospital /ID# 250283	Wakayama-shi	Wakayama
Japan	Yokohama Municipal Citizen's Hospital /ID# 248842	Yokohama-shi	Kanagawa
Korea, Republic of	CHA Bundang Medical Center /ID# 247115	???	Gyeonggido
Korea, Republic of	SMG-SNU Boramae Medical Center /ID# 248421	???
Korea, Republic of	Inje University Haeundae Hospital /ID# 244451	Busan
Korea, Republic of	Chungbuk National Univ Hosp /ID# 245168	Cheongju
Korea, Republic of	Gyeongsang National University Hospital /ID# 248420	Jinju	Gyeongsangnamdo
Korea, Republic of	Asan Medical Center /ID# 245215	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Kangbuk Samsung Hospital /ID# 248401	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Korea University Guro Hospital /ID# 244504	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 244667	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital /ID# 245218	Seoul	Seoul Teugbyeolsi
Poland	Samodzielny Publiczny Zespó? Gru?licy i Chorób P?uc w Olsztynie /ID# 250466	Olsztyn
Poland	Med Polonia Sp. z o. o. /ID# 250799	Poznan	Wielkopolskie
Poland	Wojewodzki Szpital im. Sw. Ojca Pio /ID# 251846	Przemysl	Podkarpackie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 246569	Warsaw	Mazowieckie
Puerto Rico	Pan American Center for Oncology Trials, LLC /ID# 231580	Rio Piedras
Spain	Hospital Universitario Fundacion Alcorcon /ID# 244505	Alcorcon	Madrid
Spain	Instituto Catalan de Oncologia (ICO) Badalona /ID# 245379	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona /ID# 245374	Barcelona
Spain	Hospital Universitario Vall d'Hebron /ID# 249809	Barcelona
Spain	Hospital Universitario de Jaen /ID# 249201	Jaen
Spain	Hospital General Universitario Gregorio Maranon /ID# 245270	Madrid
Spain	Hospital Universitario 12 de Octubre /ID# 248417	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 231464	Madrid
Spain	Hospital Universitario HM Sanchinarro /ID# 244721	Madrid
Spain	Clinica Universidad de Navarra - Pamplona /ID# 248816	Pamplona	Navarra
Spain	Hospital Clínico Universitario de Santiago-CHUS /ID# 245378	Santiago de Compostela	A Coruna
Spain	Hospital Universitario Virgen Macarena /ID# 245213	Sevilla
Spain	Hospital Universitario Miguel Servet /ID# 244456	Zaragoza
Taiwan	Changhua Christian Hospital /ID# 249150	Changhua City, Changhua County
Taiwan	Cmuh /Id# 245729	Taichung
Taiwan	National Cheng Kung University Hospital /ID# 245918	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center /ID# 245917	Taipei
Taiwan	Taipei Veterans General Hosp /ID# 250652	Taipei
Taiwan	National Taiwan University Hospital /ID# 245731	Taipei City
Taiwan	Taipei Medical University Hospital /ID# 245732	Taipei City
Taiwan	Tri-Service General Hospital /ID# 245733	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital /ID# 248716	Taoyuan City
United States	Univ of Colorado Cancer Center /ID# 231574	Aurora	Colorado
United States	Gabrail Cancer Center Research /ID# 248419	Canton	Ohio
United States	Duke Cancer Center /ID# 247236	Durham	North Carolina
United States	Virginia Cancer Specialists - Fairfax /ID# 231575	Fairfax	Virginia
United States	START Midwest /ID# 231551	Grand Rapids	Michigan
United States	Comprehensive Cancer Centers of Nevada /ID# 242930	Henderson	Louisiana
United States	MD Anderson Cancer Center at Texas Medical Center /ID# 248656	Houston	Texas
United States	Carolina BioOncology Institute /ID# 231541	Huntersville	North Carolina
United States	Community Health Network, Inc. /ID# 245331	Indianapolis	Indiana
United States	Indiana University Melvin and Bren Simon Cancer Center /ID# 245133	Indianapolis	Indiana
United States	University of California, Los Angeles /ID# 243841	Los Angeles	California
United States	Yale School of Medicine /ID# 248418	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 250668	New York	New York
United States	NEXT Oncology /ID# 231578	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  France,  Israel,  Japan,  Korea, Republic of,  Poland,  Puerto Rico,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Overall survival (OS)	Overall survival (OS) is defined as time from first study treatment to death due to any cause.	Up to 24 Months