Clinical trial NCT05029882: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-09-01
Enrollment: 520
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to Month 24
Secondary outcomes:
measure: Duration of Response (DOR) for Participants with Confirmed CR/PR per RECIST v1.1
timeFrame: Up to 24 Months
measure: PFS per RECIST v1.1
timeFrame: Up to 24 Months
measure: Overall survival (OS)
timeFrame: Up to 24 Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles /ID# 243841
state: California
city: Aurora
country: United States
facility: University Of Colorado Denver /ID# 231574
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine /ID# 248418
state: Connecticut
city: Chicago
country: United States
facility: University of Illinois at Chicago /ID# 251386
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology - Fort Wayne - East Dupont Road /ID# 267338
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center /ID# 245133
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network, Inc. /ID# 245331
state: Indiana
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada /ID# 242930
state: Louisiana
city: Grand Rapids
country: United States
facility: START Midwest /ID# 231551
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 250668
state: New York
city: Durham
country: United States
facility: Duke Cancer Center /ID# 247236
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 231541
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research /ID# 248419
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center at Texas Medical Center /ID# 248656
state: Texas
city: Houston
country: United States
facility: Oncology Consultants /ID# 267347
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology /ID# 231578
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax /ID# 231575
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties Tacoma /ID# 267339
state: Washington
city: South Brisbane
country: Australia
facility: Mater Misericordiae Limited /ID# 249995
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health /ID# 247667
state: Victoria
city: Bordeaux
country: France
facility: Institut Bergonie /ID# 248028
state: Gironde
city: Saint-Herblain
country: France
facility: CHU Nantes - Hopital Laennec /ID# 244723
state: Loire-Atlantique
city: St Herblain CEDEX
country: France
facility: Institut de Cancérologie de l'Ouest René Gauducheau /ID# 248399
state: Loire-Atlantique
city: Nice
country: France
facility: Centre Antoine-Lacassagne /ID# 231730
state: Provence-Alpes-Cote-d Azur
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 250987
state: Rhone
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 246824
state: Val-de-Marne
city: Dijon
country: France
facility: Centre Georges François Leclerc /ID# 244450
city: Paris
country: France
facility: AP-HP - Hopital Européen Georges Pompidou /ID# 250481
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 231218
state: H_efa
city: Kfar Saba
country: Israel
facility: Meir Medical Center /ID# 244179
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 231217
state: Tel-Aviv
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 245271
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center /ID# 243821
state: Yerushalayim
city: Petah Tikva
country: Israel
facility: Rabin Medical Center /ID# 243363
city: Nagoya-shi
country: Japan
facility: NHO Nagoya Medical Center /ID# 250286
state: Aichi
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital /ID# 250284
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 232008
state: Chiba
city: Yokohama-shi
country: Japan
facility: Yokohama Municipal Citizen's Hospital /ID# 248842
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital /ID# 250291
state: Kyoto
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital /ID# 250290
state: Nagasaki
city: Niigata-shi
country: Japan
facility: Niigata University Medical & Dental Hospital /ID# 250952
state: Niigata
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 232007
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital Of JFCR /ID# 248447
state: Tokyo
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital /ID# 250283
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Hospital /ID# 244451
state: Busan Gwang Yeogsi
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital /ID# 245168
state: Chungcheongbugdo
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center /ID# 247115
state: Gyeonggido
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital /ID# 248420
state: Gyeongsangnamdo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 244667
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital /ID# 248401
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 245215
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center /ID# 248421
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital /ID# 244504
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 245218
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 246569
state: Mazowieckie
city: Przemysl
country: Poland
facility: Wojewodzki Szpital im. Sw. Ojca Pio /ID# 251846
state: Podkarpackie
city: Poznan
country: Poland
facility: Med Polonia Sp. z o. o. /ID# 250799
state: Wielkopolskie
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zespó? Gru?licy i Chorób P?uc w Olsztynie /ID# 250466
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC /ID# 231580
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) /ID# 245378
state: A Coruna
city: Badalona
country: Spain
facility: Instituto Catalan de Oncologia (ICO) Badalona /ID# 245379
state: Barcelona
city: Alcorcon
country: Spain
facility: Hospital Universitario Fundacion Alcorcon /ID# 244505
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona /ID# 248816
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 249809
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 245374
city: Jaen
country: Spain
facility: Hospital Universitario de Jaen /ID# 249201
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon /ID# 245270
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 231464
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 248417
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 244721
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena /ID# 245213
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet /ID# 244456
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital /ID# 246449
state: Kaohsiung
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 245731
state: Taipei
city: Changhua City, Changhua County
country: Taiwan
facility: Changhua Christian Hospital /ID# 249150
city: Taichung
country: Taiwan
facility: Cmuh /Id# 245729
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 245918
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital /ID# 245732
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 250652
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center /ID# 245917
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital /ID# 245733
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 248716
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: