Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1
AbbVie (Voir sur ClinicalTrials)
octobre 2021
novembre 2027
26 juin 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Antoine HOLLEBECQUE | 27/05/2024 14:02:26 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Europeen Georges Pompidou | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine-Lacassagne /ID# 231730 - 06189 - Nice - Provence-Alpes-Cote-d Azur - France | Contact (sur clinicalTrials) | ||||
| Centre Georges François Leclerc /ID# 244450 - 21079 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Leon Berard /ID# 250987 - 69373 - Lyon CEDEX 08 - Rhone - France | Contact (sur clinicalTrials) | ||||
| CHU Nantes - Hopital Laennec /ID# 244723 - 44800 - Saint-Herblain - Loire-Atlantique - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonie /ID# 248028 - 33000 - Bordeaux - Gironde - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de l'Ouest René Gauducheau /ID# 248399 - 44805 - St Herblain CEDEX - Loire-Atlantique - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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.
- 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.