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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05029882




Registration number
NCT05029882
Ethics application status
Date submitted
30/08/2021
Date registered
1/09/2021
Date last updated
13/11/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2023-509335-60-00
Secondary ID [2] 0 0
M21-404
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Advanced Solid Tumors 0 0
Gastroesophageal Adenocarcinoma 0 0
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABBV-400
Treatment: Drugs - Trifluridine/Tipiracil
Treatment: Drugs - Bevacizumab

Experimental: Part 1 (Monotherapy Dose Escalation) - Participants with advanced solid tumors will receive escalating doses of ABBV-400.

Experimental: 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).

Experimental: Part 2ii (mutEGFR NSCLC) - Participants with non-Squamous mutEGFR NSCLC will receive ABBV-400 at RP2D.

Experimental: Part 2iii (Squamous NSCLC) - Participants with squamous NSCLC will receive ABBV-400 at RP2D.

Experimental: Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct - Participants with gastroesophageal adenocarcinoma will receive ABBV-400 at the RP2D.

Experimental: Part 4 (Colorectal Cancer) - Participants with Colorectal Cancer (CRC) will receive ABBV-400 at the RP2D and various dose levels for dose optimization.

Experimental: 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.

Experimental: Part 6 (MET Mutation) - Participants with MET mutation will receive ABBV-400 at the RP2D and various dose levels for dose optimization.

Experimental: Part 7a (Combination Dose Escalation) - Participants with CRC will receive escalating doses of ABBV-400 in combination with bevacizumab.

Experimental: 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.

Experimental: 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.

Experimental: Part 7biii (Combination Comparator) - Participants with CRC will receive trifluridine/tipiracil (TAS-102) in combination with bevacizumab.


Treatment: Drugs: ABBV-400
Intravenous (IV) Infusion

Treatment: Drugs: Trifluridine/Tipiracil
Oral Tablet

Treatment: Drugs: Bevacizumab
IV Infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to Month 24
Secondary outcome [1] 0 0
Duration of Response (DOR) for Participants with Confirmed CR/PR per RECIST v1.1
Timepoint [1] 0 0
Up to 24 Months
Secondary outcome [2] 0 0
PFS per RECIST v1.1
Timepoint [2] 0 0
Up to 24 Months
Secondary outcome [3] 0 0
Overall survival (OS)
Timepoint [3] 0 0
Up to 24 Months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/11/2025
Actual
Sample size
Target
500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Mater Misericordiae Limited /ID# 249995 - South Brisbane
Recruitment hospital [2] 0 0
Austin Health /ID# 247667 - Heidelberg
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
France
State/province [14] 0 0
Gironde
Country [15] 0 0
France
State/province [15] 0 0
Loire-Atlantique
Country [16] 0 0
France
State/province [16] 0 0
Provence-Alpes-Cote-d Azur
Country [17] 0 0
France
State/province [17] 0 0
Rhone
Country [18] 0 0
France
State/province [18] 0 0
Val-de-Marne
Country [19] 0 0
France
State/province [19] 0 0
Dijon
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
Israel
State/province [21] 0 0
H_efa
Country [22] 0 0
Israel
State/province [22] 0 0
HaMerkaz
Country [23] 0 0
Israel
State/province [23] 0 0
Tel-Aviv
Country [24] 0 0
Israel
State/province [24] 0 0
Yerushalayim
Country [25] 0 0
Israel
State/province [25] 0 0
Haifa
Country [26] 0 0
Japan
State/province [26] 0 0
Aichi
Country [27] 0 0
Japan
State/province [27] 0 0
Chiba
Country [28] 0 0
Japan
State/province [28] 0 0
Kanagawa
Country [29] 0 0
Japan
State/province [29] 0 0
Kyoto
Country [30] 0 0
Japan
State/province [30] 0 0
Nagasaki
Country [31] 0 0
Japan
State/province [31] 0 0
Niigata
Country [32] 0 0
Japan
State/province [32] 0 0
Tokyo
Country [33] 0 0
Japan
State/province [33] 0 0
Wakayama
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Busan Gwang Yeogsi
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Chungcheongbugdo
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Gyeonggido
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Gyeongsangnamdo
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul Teugbyeolsi
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Seoul
Country [40] 0 0
Poland
State/province [40] 0 0
Mazowieckie
Country [41] 0 0
Poland
State/province [41] 0 0
Podkarpackie
Country [42] 0 0
Poland
State/province [42] 0 0
Wielkopolskie
Country [43] 0 0
Poland
State/province [43] 0 0
Olsztyn
Country [44] 0 0
Puerto Rico
State/province [44] 0 0
Rio Piedras
Country [45] 0 0
Spain
State/province [45] 0 0
A Coruna
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Spain
State/province [48] 0 0
Navarra
Country [49] 0 0
Spain
State/province [49] 0 0
Jaen
Country [50] 0 0
Spain
State/province [50] 0 0
Sevilla
Country [51] 0 0
Spain
State/province [51] 0 0
Zaragoza
Country [52] 0 0
Taiwan
State/province [52] 0 0
Kaohsiung
Country [53] 0 0
Taiwan
State/province [53] 0 0
Taipei
Country [54] 0 0
Taiwan
State/province [54] 0 0
Changhua City, Changhua County
Country [55] 0 0
Taiwan
State/province [55] 0 0
Taichung
Country [56] 0 0
Taiwan
State/province [56] 0 0
Tainan
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taipei City
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taoyuan City

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05029882
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05029882