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
- Conditions
- Colorectal CancerAdvanced Solid TumorsNon-Small Cell Lung CancerGastroesophageal Adenocarcinoma
- Interventions
- Registration Number
- NCT05029882
- Lead Sponsor
- AbbVie
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 520
-
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2i (wtEGFR Non-Small Cell Lung Cancer [NSCLC]) ABBV-400 Participants with non-squamous wtEGFR NSCLC will receive ABBV-400 at the Recommended Phase 2 dose (RP2D). Part 1 (Monotherapy Dose Escalation) ABBV-400 Participants with advanced solid tumors will receive escalating doses of ABBV-400. Part 2ii (mutEGFR NSCLC) ABBV-400 Participants with non-Squamous mutEGFR NSCLC will receive ABBV-400 at RP2D. Part 6 (MET Mutation) ABBV-400 Participants with MET mutation will receive ABBV-400 at the RP2D and various dose levels for dose optimization. Part 2iii (Squamous NSCLC) ABBV-400 Participants with squamous NSCLC will receive ABBV-400 at RP2D. Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct ABBV-400 Participants with gastroesophageal adenocarcinoma will receive ABBV-400 at the RP2D. Part 7biii (Combination Comparator) Trifluridine/Tipiracil Participants with CRC will receive trifluridine/tipiracil (TAS-102) in combination with bevacizumab. Part 7biii (Combination Comparator) Bevacizumab Participants with CRC will receive trifluridine/tipiracil (TAS-102) in combination with bevacizumab. Part 7a (Combination Dose Escalation) ABBV-400 Participants with CRC will receive escalating doses of ABBV-400 in combination with bevacizumab. Part 4 (Colorectal Cancer) ABBV-400 Participants with Colorectal Cancer (CRC) will receive ABBV-400 at the RP2D and various dose levels for dose optimization. Part 7bii (Combination Dose Optimization High Dose) ABBV-400 Participants with CRC will receive the high dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab. Part 5 (MET Amplification) ABBV-400 Participants with mesenchymal-epithelial transition proto-oncogene (MET) amplification will receive ABBV-400 at the RP2D and various dose levels for dose optimization. Part 7bi (Combination Dose Optimization Low Dose) ABBV-400 Participants with CRC will receive the low dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab. Part 7a (Combination Dose Escalation) Bevacizumab Participants with CRC will receive escalating doses of ABBV-400 in combination with bevacizumab. Part 7bi (Combination Dose Optimization Low Dose) Bevacizumab Participants with CRC will receive the low dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab. Part 7bii (Combination Dose Optimization High Dose) Bevacizumab Participants with CRC will receive the high dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to Month 24 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) for Participants with Confirmed CR/PR per RECIST v1.1 Up to 24 Months 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.
Overall survival (OS) Up to 24 Months Overall survival (OS) is defined as time from first study treatment to death due to any cause.
PFS per RECIST v1.1 Up to 24 Months 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.
Trial Locations
- Locations (82)
Centre Georges François Leclerc /ID# 244450
🇫🇷Dijon, France
AP-HP - Hopital Européen Georges Pompidou /ID# 250481
🇫🇷Paris, France
Rambam Health Care Campus /ID# 231218
🇮🇱Haifa, H_efa, 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, Israel
Hadassah Medical Center /ID# 243821
🇮🇱Jerusalem, Yerushalayim, Israel
Rabin Medical Center /ID# 243363
🇮🇱Petah Tikva, Israel
NHO Nagoya Medical Center /ID# 250286
🇯🇵Nagoya-shi, Aichi, Japan
Aichi Cancer Center Hospital /ID# 250284
🇯🇵Nagoya-shi, Aichi, Japan
National Cancer Center Hospital East /ID# 232008
🇯🇵Kashiwa-shi, Chiba, Japan
Yokohama Municipal Citizen's Hospital /ID# 248842
🇯🇵Yokohama-shi, Kanagawa, Japan
Kyoto University Hospital /ID# 250291
🇯🇵Kyoto-shi, Kyoto, Japan
Nagasaki University Hospital /ID# 250290
🇯🇵Nagasaki-shi, Nagasaki, Japan
Niigata University Medical & Dental Hospital /ID# 250952
🇯🇵Niigata-shi, 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, Japan
Inje University Haeundae Hospital /ID# 244451
🇰🇷Busan, Busan Gwang Yeogsi, Korea, Republic of
Chungbuk National University Hospital /ID# 245168
🇰🇷Cheongju, Chungcheongbugdo, Korea, Republic of
CHA Bundang Medical Center /ID# 247115
🇰🇷Seongnam, Gyeonggido, Korea, Republic of
Gyeongsang National University Hospital /ID# 248420
🇰🇷Jinju, Gyeongsangnamdo, Korea, Republic of
Seoul National University Hospital /ID# 244667
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
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
Hospital Universitario Vall d'Hebron /ID# 249809
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona /ID# 245374
🇪🇸Barcelona, Spain
Hospital Universitario de Jaen /ID# 249201
🇪🇸Jaen, 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
🇪🇸Sevilla, Spain
Hospital Universitario Miguel Servet /ID# 244456
🇪🇸Zaragoza, Spain
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, Taiwan
Taipei Medical University Hospital /ID# 245732
🇨🇳Taipei City, 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 City, Taiwan
Austin Health /ID# 247667
🇦🇺Heidelberg, Victoria, Australia
University of Illinois at Chicago /ID# 251386
🇺🇸Chicago, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center /ID# 245133
🇺🇸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 Center /ID# 247236
🇺🇸Durham, North Carolina, United States
Carolina BioOncology Institute /ID# 231541
🇺🇸Huntersville, North Carolina, United States
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
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
Fort Wayne Medical Oncology and Hematology - Fort Wayne - East Dupont Road /ID# 267338
🇺🇸Fort Wayne, Indiana, United States
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
🇫🇷St Herblain CEDEX, Loire-Atlantique, France
Centre Antoine-Lacassagne /ID# 231730
🇫🇷Nice, Provence-Alpes-Cote-d Azur, France
Centre Leon Berard /ID# 250987
🇫🇷Lyon CEDEX 08, Rhone, France
Institut Gustave Roussy /ID# 246824
🇫🇷Villejuif Cedex, Val-de-Marne, France
Community Health Network, Inc. /ID# 245331
🇺🇸Indianapolis, Indiana, United States
Kangbuk Samsung Hospital /ID# 248401
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center /ID# 245215
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
SMG-SNU Boramae Medical Center /ID# 248421
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Korea University Guro Hospital /ID# 244504
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Yonsei University Health System Severance Hospital /ID# 245218
🇰🇷Seoul, Korea, Republic of
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 246569
🇵🇱Warsaw, Mazowieckie, Poland
Wojewodzki Szpital im. Sw. Ojca Pio /ID# 251846
🇵🇱Przemysl, Podkarpackie, Poland
Med Polonia Sp. z o. o. /ID# 250799
🇵🇱Poznan, Wielkopolskie, Poland
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
🇪🇸Alcorcon, Madrid, Spain
Clinica Universidad de Navarra - Pamplona /ID# 248816
🇪🇸Pamplona, Navarra, Spain