Informations générales (source: ClinicalTrials.gov)
An Open-Label, Dose Escalation and Dose Expansion Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered CA-4948 in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma
Interventional
Phase 1/Phase 2
Curis, Inc. (Voir sur ClinicalTrials)
décembre 2017
octobre 2026
05 avril 2025
This is a multi-center, open-label study to evaluate the safety, pharmacokinetics (PK),
and anti-cancer activity of oral administration of emavusertib alone or in combination
with ibrutinib in adult participants with relapsed or refractory (R/R) hematologic
malignancies.
This trial will be completed in four parts. In Part A1, emavusertib will be evaluated
first in a dose escalating monotherapy setting to establish the safety and tolerability
(complete). In Part A2, emavusertib will be evaluated in combination with ibrutinib at
560 milligrams (mg) once daily (QD) or 420 mg QD as indicated by disease (Part A2
complete).
Part B will comprise 2 cohorts to assess safety and efficacy of emavusertib in
combination with ibrutinib in participants with R/R primary central nervous system
lymphoma (PCNSL) who have directly progressed on a bruton tyrosine kinase inhibitor
(BTKi). In this part of the study, emavusertib will be dosed at 100 mg or 200 mg twice
daily (BID) in combination with ibrutinib in 28-day treatment cycles.
Part C will comprise 3 treatment arms in the second-line setting to assess the efficacy
and safety of emavusertib monotherapy, ibrutinib monotherapy, and emavusertib in
combination with ibrutinib in participants with R/R PCNSL who are naïve to BTKi
treatment. In this part of the study, eligible second-line participants with R/R PCNSL
who are naïve to BTKi treatment will be randomized 1:1:1 to 1 of 3 treatment arms: (1)
emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in
combination with ibrutinib 560 mg QD.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/06/2024 14:01:16 | Contact (sur clinicalTrials) | |||
| CLCC RENE HUGUENIN INSTITUT CURIE | 10/04/2025 13:11:55 | Contact (sur clinicalTrials) | |||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital La Pitié-Salpêtrière | 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 | |||||
| Hopital de la Timone - Marseille - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonie - Bordeaux - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
1. Males and females greater than or equal to 18 years of age
2. Life expectancy of at least 3 months
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable).
Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
1. Participants with parenchymal lesions must have unequivocal evidence of disease
progression (e.g., presence of at least 1 measurable target lesion [≥ 10
millimeters (mm) and ≤ 40 mm in the longest diameter on brain magnetic
resonance imaging [MRI] or head computed tomography [CT] on imaging within 28
days prior to Cycle 1 Day 1]). In cases where the tumor size is smaller but
still measurable and located at a critical central nervous system (CNS)
location, disabling the participant and/or causing symptoms, this participant
may be eligible following a discussion with the Sponsor Medical Monitor.
2. For participants limited to leptomeningeal involvement, cerebrospinal fluid
(CSF) analysis (cytology and/or flow cytometry) with or without additional
imaging (MRI) of the spine as clinically indicated is required to document
abnormal cells within 28 days prior to Cycle 1 Day 1.
Exclusion Criteria for Part B and Part C
1. Participants with only intraocular PCNSL without brain lesion or CSF involvement,
T-cell lymphoma, systemic presence of lymphoma, or non-CNS lymphoma metastatic to
the CNS
2. Evidence of systemic lymphoma. This must be demonstrated by a positron emission
tomography (PET) scan (or CT scan with contrast if applicable) of the chest,
abdomen, and pelvis at Screening (testicular ultrasound may be considered to exclude
a testicular lymphoma disseminated to the brain).
3. Prior history of malignancies other than lymphoma (except for basal cell or squamous
cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior
history of systemic lymphoma, unless the participant has been free of the disease
for ≥ 3 years.
4. Active malignancy other than PCNSL requiring systemic therapy
5. Previous BTKi treatment (Part C only).
6. History of Grade ≥ 3 rhabdomyolysis without complete recovery
7. Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.
8. Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1
Day 1.
9. Received prior investigational drugs (including treatment in clinical research,
unapproved combination products, and new dosage forms) within 28 days or 5
half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic
stem cell transplant (HSCT) within 60 days prior to Cycle 1 Day 1; or had clinically
significant graft-versus-host disease (GVHD) requiring ongoing up-titration of
immunosuppressive medications prior to Screening (with the exception of a BTKi for
Part B only).
Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT
and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical
Monitor approval
10. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug
therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior
to Cycle 1 Day 1 (with the exception of ibrutinib or other BTKi for Part B only,
which may be continued until the day before Cycle 1 Day 1)
11. Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of
their excipients.
1. Males and females greater than or equal to 18 years of age
2. Life expectancy of at least 3 months
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable).
Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
1. Participants with parenchymal lesions must have unequivocal evidence of disease
progression (e.g., presence of at least 1 measurable target lesion [≥ 10
millimeters (mm) and ≤ 40 mm in the longest diameter on brain magnetic
resonance imaging [MRI] or head computed tomography [CT] on imaging within 28
days prior to Cycle 1 Day 1]). In cases where the tumor size is smaller but
still measurable and located at a critical central nervous system (CNS)
location, disabling the participant and/or causing symptoms, this participant
may be eligible following a discussion with the Sponsor Medical Monitor.
2. For participants limited to leptomeningeal involvement, cerebrospinal fluid
(CSF) analysis (cytology and/or flow cytometry) with or without additional
imaging (MRI) of the spine as clinically indicated is required to document
abnormal cells within 28 days prior to Cycle 1 Day 1.
Exclusion Criteria for Part B and Part C
1. Participants with only intraocular PCNSL without brain lesion or CSF involvement,
T-cell lymphoma, systemic presence of lymphoma, or non-CNS lymphoma metastatic to
the CNS
2. Evidence of systemic lymphoma. This must be demonstrated by a positron emission
tomography (PET) scan (or CT scan with contrast if applicable) of the chest,
abdomen, and pelvis at Screening (testicular ultrasound may be considered to exclude
a testicular lymphoma disseminated to the brain).
3. Prior history of malignancies other than lymphoma (except for basal cell or squamous
cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior
history of systemic lymphoma, unless the participant has been free of the disease
for ≥ 3 years.
4. Active malignancy other than PCNSL requiring systemic therapy
5. Previous BTKi treatment (Part C only).
6. History of Grade ≥ 3 rhabdomyolysis without complete recovery
7. Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.
8. Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1
Day 1.
9. Received prior investigational drugs (including treatment in clinical research,
unapproved combination products, and new dosage forms) within 28 days or 5
half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic
stem cell transplant (HSCT) within 60 days prior to Cycle 1 Day 1; or had clinically
significant graft-versus-host disease (GVHD) requiring ongoing up-titration of
immunosuppressive medications prior to Screening (with the exception of a BTKi for
Part B only).
Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT
and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical
Monitor approval
10. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug
therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior
to Cycle 1 Day 1 (with the exception of ibrutinib or other BTKi for Part B only,
which may be continued until the day before Cycle 1 Day 1)
11. Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of
their excipients.