Informations générales (source: ClinicalTrials.gov)
A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-706 as Monotherapy and in Combination With Budigalimab (ABBV-181), Carboplatin, or Cisplatin in Adult Subjects With Advanced Solid Tumors
Interventional
Phase 1
AbbVie (Voir sur ClinicalTrials)
décembre 2022
novembre 2027
31 mai 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 safety, tolerability,
pharmacokinetics and preliminary efficacy of ABBV-706 as a monotherapy and in combination
with budigalimab, carboplatin, or cisplatin.
ABBV-706 is an investigational drug being developed for the treatment of small cell lung
cancer (SCLC), high-grade central nervous system (CNS) tumors and high-grade
neuroendocrine carcinomas (NECs). There are multiple treatment arms in this study.
Participants will either receive ABBV-706 as a single agent or in combination with
budigalimab (another investigational drug), carboplatin or cisplatin at different doses.
Approximately 350 adult participants will be enrolled in the study across sites
worldwide.
In part 1 (dose escalation), ABBV-706 will be intravenously infused in escalating doses
as a monotherapy until the maximum tolerated dose (MTD) is determined in participants
with SCLC, high-grade CNS tumors, and high-grade NECs. In part 2, multiple doses will be
selected from Part 1 and SCLC participants will be assigned to one of these doses in a
randomized fashion to determine the recommended Phase 2 dose. In Part 3a, participants
with SCLC or NECs will receive ABBV-706 in combination with budigalimab intravenously
every 3 weeks. In Part 3b participants with SCLC or NECs will receive ABBV-706 in
combination with either carboplatin or cisplatin intravenously. In Part 4a, participants
with CNS tumors will receive ABBV-706 intravenously at a dose determined from Part 1. In
Part 4b, participants with NECs will receive ABBV-706 intravenously at a dose selected
from Part 1. The estimated duration of the study is up to 3 years.
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 a hospital
or clinic and may require frequent medical assessments, blood tests, and scans.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | 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 | |||||
| Institut Bergonie /ID# 258655 - 33000 - Bordeaux - Gironde - France | Contact (sur clinicalTrials) | ||||
| Institut Régional du Cancer Montpellier /ID# 265086 - 34298 - Montpellier - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- The laboratory values criteria must be met within 7 days prior to the first dose of
study drug as per the protocol.
- QT interval corrected for heart rate (QTc) <= 450 msec (males) or <= 470 msec
(females) using Fridericia's correction, and an ejection fraction of >= 50% as
measured by echocardiogram or multigated acquisition (MUGA) scan at Screening.
- Part 1 only: Advanced recurrent or refractory solid tumors with potential SEZ6
expression including small cell lung cancer (SCLC), high-grade central nervous
system (CNS) tumors (glioblastoma [GBM], IDH-wildtype Grade 4; oligodendroglioma,
IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade
4), neuroendocrine prostate cancer (NEPC), high-grade poorly differentiated
gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)s, large cell
neuroendocrine carcinoma (LCNEC)s, SCLC transformed from epidermal growth factor
receptor (EGFR) mutant non-small cell lung cancer (NSCLC), atypical lung carcinoids,
and other high-grade poorly differentiated NECs, who have progressed on or after
standard of care (SoC) therapy and with no curative therapy available. For SCLC,
participants must have histologically or cytologically confirmed SCLC that is
relapsed or refractory following at least 1 prior platinum-containing chemotherapy.
- Part 2 only: Histologically or cytologically confirmed SCLC that is relapsed or
refractory (R/R) following at least 1 prior platinum-containing chemotherapy and
with no curative therapy available. For the purposes of this study, a line of
therapy is defined as >= 1 complete cycle of either a single agent or combination of
drugs, including any planned sequential therapy of various regimens.
- Part 3a only: Participants with R/R SCLC following at least 1 prior
platinum-containing chemotherapy or R/R poorly differentiated NECs, e.g., NEPC,
GEP-NECs, LCNECs, SCLC transformed from EGFR mutant Non-small cell lung cancer
(NSCLC), atypical lung carcinoids, other high-grade poorly differentiated NECs.
- Part 3b only: Participants with R/R SCLC who have only progressed following a
frontline regimen containing a platinum-based chemotherapy or R/R NECs, e.g., NEPC,
GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids,
other NECs.
- Part 4a only: Participants with R/R high-grade CNS tumors (GBM, IDH-wildtype Grade
4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma,
IDH-mutant Grade 3 or Grade 4) who have progressed on SoC therapy and with no
curative therapy options available.
- Part 4b only: Participants with R/R neuroendocrine tumors, including NEPC, GEP-NECs,
LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, and other
high-grade poorly differentiated NECs, who have progressed on SoC therapy and with
no curative therapy options available.
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1 for participants with extracranial solid tumors or Response Assessment for
Neuro-Oncology (RANO)for participants with primary high-grade CNS tumors (GBM,
IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3;
astrocytoma, IDH-mutant Grade 3 or Grade 4).
- Primary CNS tumors within 12 weeks from radiation therapy should have unequivocal
progression as documented by either tumor recurrence predominantly outside of
radiation field on magnetic resonance imaging (MRI) or confirmed on tumor biopsy.
- Participants with brain metastases from an extracranial solid tumor are eligible if
the brain metastases as outlined in the protocol.
- Fresh or archival tumor tissue available for submission, for retrospective SEZ6
expression analysis as outlined in the protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- The laboratory values criteria must be met within 7 days prior to the first dose of
study drug as per the protocol.
- QT interval corrected for heart rate (QTc) <= 450 msec (males) or <= 470 msec
(females) using Fridericia's correction, and an ejection fraction of >= 50% as
measured by echocardiogram or multigated acquisition (MUGA) scan at Screening.
- Part 1 only: Advanced recurrent or refractory solid tumors with potential SEZ6
expression including small cell lung cancer (SCLC), high-grade central nervous
system (CNS) tumors (glioblastoma [GBM], IDH-wildtype Grade 4; oligodendroglioma,
IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade
4), neuroendocrine prostate cancer (NEPC), high-grade poorly differentiated
gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)s, large cell
neuroendocrine carcinoma (LCNEC)s, SCLC transformed from epidermal growth factor
receptor (EGFR) mutant non-small cell lung cancer (NSCLC), atypical lung carcinoids,
and other high-grade poorly differentiated NECs, who have progressed on or after
standard of care (SoC) therapy and with no curative therapy available. For SCLC,
participants must have histologically or cytologically confirmed SCLC that is
relapsed or refractory following at least 1 prior platinum-containing chemotherapy.
- Part 2 only: Histologically or cytologically confirmed SCLC that is relapsed or
refractory (R/R) following at least 1 prior platinum-containing chemotherapy and
with no curative therapy available. For the purposes of this study, a line of
therapy is defined as >= 1 complete cycle of either a single agent or combination of
drugs, including any planned sequential therapy of various regimens.
- Part 3a only: Participants with R/R SCLC following at least 1 prior
platinum-containing chemotherapy or R/R poorly differentiated NECs, e.g., NEPC,
GEP-NECs, LCNECs, SCLC transformed from EGFR mutant Non-small cell lung cancer
(NSCLC), atypical lung carcinoids, other high-grade poorly differentiated NECs.
- Part 3b only: Participants with R/R SCLC who have only progressed following a
frontline regimen containing a platinum-based chemotherapy or R/R NECs, e.g., NEPC,
GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids,
other NECs.
- Part 4a only: Participants with R/R high-grade CNS tumors (GBM, IDH-wildtype Grade
4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma,
IDH-mutant Grade 3 or Grade 4) who have progressed on SoC therapy and with no
curative therapy options available.
- Part 4b only: Participants with R/R neuroendocrine tumors, including NEPC, GEP-NECs,
LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, and other
high-grade poorly differentiated NECs, who have progressed on SoC therapy and with
no curative therapy options available.
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1 for participants with extracranial solid tumors or Response Assessment for
Neuro-Oncology (RANO)for participants with primary high-grade CNS tumors (GBM,
IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3;
astrocytoma, IDH-mutant Grade 3 or Grade 4).
- Primary CNS tumors within 12 weeks from radiation therapy should have unequivocal
progression as documented by either tumor recurrence predominantly outside of
radiation field on magnetic resonance imaging (MRI) or confirmed on tumor biopsy.
- Participants with brain metastases from an extracranial solid tumor are eligible if
the brain metastases as outlined in the protocol.
- Fresh or archival tumor tissue available for submission, for retrospective SEZ6
expression analysis as 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 pneumonitis.
- History of idiopathic pulmonary fibrosis or organizing pneumonia.
- Prior treatment with an antibody drug conjugate that consists of a Top1 inhibitor
payload.
- Part 2 only: Prior treatment with a SEZ6-targeted antibody drug conjugate.