Informations générales (source: ClinicalTrials.gov)
A Phase 1/2 Study of DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas
Interventional
Phase 1/Phase 2
Novartis Pharmaceuticals (Voir sur ClinicalTrials)
septembre 2019
février 2030
16 mai 2025
The purpose of this open-label, first-in-human (FIH) trial is to evaluate the safety,
tolerability, and preliminary clinical activity of Tulmimetostat as a monotherapy in
patients with advanced solid tumors and lymphomas.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Vincent RIBRAG | 17/05/2024 14:36:01 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Bergonie Institute - 33000 - Bordeaux - France | Laura Wanner | Contact (sur clinicalTrials) | |||
| Leon Berard Center - 69373 - Lyon - France | Emilie Repetto | Contact (sur clinicalTrials) | |||
| Nantes University Hospital Center - Hotel Dieu Hospital - 44093 - Nantes - France | Tiphaine Chiron | Contact (sur clinicalTrials) | |||
| Nantes University Hospital Center - Hotel Dieu Hospital (Satellite) - 44093 - Nantes - France | Claire Peluchon | Contact (sur clinicalTrials) | |||
| Nord Laennec Hospital - 44800 - Saint-Herblain - France | Helene Godet | Contact (sur clinicalTrials) | |||
| Oscar Lambret Center - 59020 - Lille - France | Solaya Chalal | Contact (sur clinicalTrials) | |||
| Strasbourg Europe Institut of Cancerology - 67200 - Strasbourg - France | Lucie-Anne Casper | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Eligible Phase 1 patients are adults who have a confirmed locally advanced or
metastatic tumors (solid tumors or lymphoma) that have relapsed following standard
therapy or progressed through standard therapy or who have a disease for which no
standard effective therapy exists.
- Eligible Phase 2 patients in cohorts M1 to M3 are adults who are known to have the
ARID1A mutation by next-generation sequencing (NGS) testing; have measurable disease
per Response Evaluation Criteria in Solid Tumors 1.1 and who have confirmed relapsed
urothelial or other advanced/metastatic solid tumors (M1), ovarian clear cell
carcinoma (M2), or endometrial carcinoma (M3).
- Eligible Phase 2 patients in Cohort M4 are adults who have either relapsed or
refractory PTCL (at least 10 patients) or DLBCL (up to 10 patients), including
patients with documented GCB DLBCL with EZH2 hotspot mutation. Patients with PTCL
must have at least 1 prior line of therapy and patients with DLBCL must have at
least 2 prior lines of standard therapy; and are not considered candidates to
receive CAR-T or ASCT therapy.
- Eligible Phase 2 patients in Cohort M5 are adults who are known to the have the BAP1
loss, have malignant pleural or peritoneal mesothelioma, and have progressed on at
least 1 prior line of active therapy.
- Eligible Phase 2 patients in Cohort M6 are adults who have mCRPC with measurable
soft tissue disease with CT scan as defined by PCWG3 criteria, have baseline
testosterone levels ≤ 50 ng/dL (≤ 2.0 nM) and have surgical or ongoing medical
castration and who have progressed on at least 1 androgen-receptor signaling
inhibitor and at least 1 taxane-based chemotherapy (cabazitaxel, France only).
- Eligible Phase 2 patients in Cohort M7 are adults with recurrent, advanced ARID1A WT
endometrial carcinoma confirmed by NGS testing and have measurable disease per
Response Evaluation Criteria in Solid Tumors 1.1 Patients will be enrolled with
maximum up to 2 prior lines of systemic therapy for treating endometrial carcinoma
that must include at least one treatment line with systemic platinum-based
chemotherapy in advanced/ recurrent disease setting, and anti-programmed cell death
protein 1 (PD-1)/ anti-programmed death-ligand 1 (PD-L1) therapy, either in
combination or separately, unless these are contraindicated or are not locally
accessible.
- Eligible Part 1 and Part 2 patients in Cohort M8 are adults who have mCRPC with
measurable soft tissue disease as per PCWG3 criteria, have baseline testosterone
levels ≤ 50 ng/dL (≤ 2.0 nM), have surgical or ongoing medical castration or hormone
sensitive prostate cancer (HSPC) disease stage. In addition, Eligible part 1
patients in Cohort M8 may have received abiraterone treatment in mCRPC while
eligible part 2 patients in Cohort M8 must have received abiraterone treatment in
mCRPC. In addition, only for M8 Part 1: Patients may have received no more than one
previous regimen of taxane-based chemotherapy in mCRPC or HSPC setting. For M8 Part
2: Patients may have received no more than one previous regimen of taxane-based
chemotherapy in HSPC setting. Patients for both M8 Part 1 and M8 Part 2 must have
evidence of prostate cancer progression (per PCWG3) and must have ongoing ADT
(androgen deprivation therapy) with a GnRH analogue, antagonist or bilateral
orchiectomy (i.e., surgical or medical castration).
- All patients will have Eastern Cooperative Oncology Group (ECOG) performance status
of ≤ 1 and adequate organ function.
Key
- Eligible Phase 1 patients are adults who have a confirmed locally advanced or
metastatic tumors (solid tumors or lymphoma) that have relapsed following standard
therapy or progressed through standard therapy or who have a disease for which no
standard effective therapy exists.
- Eligible Phase 2 patients in cohorts M1 to M3 are adults who are known to have the
ARID1A mutation by next-generation sequencing (NGS) testing; have measurable disease
per Response Evaluation Criteria in Solid Tumors 1.1 and who have confirmed relapsed
urothelial or other advanced/metastatic solid tumors (M1), ovarian clear cell
carcinoma (M2), or endometrial carcinoma (M3).
- Eligible Phase 2 patients in Cohort M4 are adults who have either relapsed or
refractory PTCL (at least 10 patients) or DLBCL (up to 10 patients), including
patients with documented GCB DLBCL with EZH2 hotspot mutation. Patients with PTCL
must have at least 1 prior line of therapy and patients with DLBCL must have at
least 2 prior lines of standard therapy; and are not considered candidates to
receive CAR-T or ASCT therapy.
- Eligible Phase 2 patients in Cohort M5 are adults who are known to the have the BAP1
loss, have malignant pleural or peritoneal mesothelioma, and have progressed on at
least 1 prior line of active therapy.
- Eligible Phase 2 patients in Cohort M6 are adults who have mCRPC with measurable
soft tissue disease with CT scan as defined by PCWG3 criteria, have baseline
testosterone levels ≤ 50 ng/dL (≤ 2.0 nM) and have surgical or ongoing medical
castration and who have progressed on at least 1 androgen-receptor signaling
inhibitor and at least 1 taxane-based chemotherapy (cabazitaxel, France only).
- Eligible Phase 2 patients in Cohort M7 are adults with recurrent, advanced ARID1A WT
endometrial carcinoma confirmed by NGS testing and have measurable disease per
Response Evaluation Criteria in Solid Tumors 1.1 Patients will be enrolled with
maximum up to 2 prior lines of systemic therapy for treating endometrial carcinoma
that must include at least one treatment line with systemic platinum-based
chemotherapy in advanced/ recurrent disease setting, and anti-programmed cell death
protein 1 (PD-1)/ anti-programmed death-ligand 1 (PD-L1) therapy, either in
combination or separately, unless these are contraindicated or are not locally
accessible.
- Eligible Part 1 and Part 2 patients in Cohort M8 are adults who have mCRPC with
measurable soft tissue disease as per PCWG3 criteria, have baseline testosterone
levels ≤ 50 ng/dL (≤ 2.0 nM), have surgical or ongoing medical castration or hormone
sensitive prostate cancer (HSPC) disease stage. In addition, Eligible part 1
patients in Cohort M8 may have received abiraterone treatment in mCRPC while
eligible part 2 patients in Cohort M8 must have received abiraterone treatment in
mCRPC. In addition, only for M8 Part 1: Patients may have received no more than one
previous regimen of taxane-based chemotherapy in mCRPC or HSPC setting. For M8 Part
2: Patients may have received no more than one previous regimen of taxane-based
chemotherapy in HSPC setting. Patients for both M8 Part 1 and M8 Part 2 must have
evidence of prostate cancer progression (per PCWG3) and must have ongoing ADT
(androgen deprivation therapy) with a GnRH analogue, antagonist or bilateral
orchiectomy (i.e., surgical or medical castration).
- All patients will have Eastern Cooperative Oncology Group (ECOG) performance status
of ≤ 1 and adequate organ function.
Key
1. Medical Conditions
- Previous solid organ or allogeneic hematopoietic cell transplantation (HCT).
- Known symptomatic untreated brain metastases. Patients with central nervous
system (CNS) metastases must have stable neurologic status following local
therapy for at least 4 weeks on a stable or decreasing dose of steroids (≤ 10
mg daily prednisone or equivalent). Patients in the M4 lymphoma cohort are
excluded if they have known CNS involvement by lymphoma.
- Clinically significant cardiovascular disease, including:
- Myocardial infarction or stroke within 3 months (6 months for M8 cohort)
prior to Day 1 of treatment.
- Unstable angina within 3 months (6 months for M8 cohort) prior to Day 1 of
treatment.
- Congestive heart failure or cardiomyopathy with New York Heart Association
(NYHA) Class 3 or 4.
- History of clinically significant ventricular arrhythmias (e.g.,
ventricular tachycardia, ventricular fibrillation, torsades de pointes).
- Uncontrolled hypertension despite 2 concomitant antihypertensive
therapies.
- For Cohorts M1-M6: QT interval corrected by the Fridericia correction
formula (QTcF) > 480 msec on the Screening ECG.
- For Cohorts M7 and M8: QTcF interval ≥ 450 msec at screening.
- Major surgery within 4 weeks before starting study drug or not recovered from
any effects of prior major surgery (uncomplicated central line placement or
fine needle aspirate are not considered major surgery).
- Gastrointestinal disorders that may significantly interfere with the absorption
of the study medication, such as ulcerative colitis, malabsorption syndrome,
refractory nausea and vomiting, biliary shunt, significant bowel resection.
- Uncontrolled active infection requiring intravenous antibiotic, antiviral, or
antifungal medications within 14 days before the first dose of study drug.
Controlled infections on concurrent antimicrobial agents and antimicrobial
prophylaxis per institutional guidelines are acceptable.
- Suspected pneumonitis or interstitial lung disease (confirmed by radiography or
CT) or a history of these conditions.
- History of a concurrent or second malignancy except for certain adequately
treated cancers such as local basal cell or squamous cell carcinoma of the
skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic
prostate cancer without known metastatic disease, adequately treated Stage 1 or
2 cancer currently in complete remission, or any other cancer in complete
remission for ≥ 3 years. Patients with a history of T-cell lymphoblastic
lymphoma or T-cell lymphoblastic leukemia are not eligible.
- Current known active or chronic infection with HIV, hepatitis B, or hepatitis
C. Screening for these viruses is not required unless there is a past history
or current suspicion of viral hepatitis.
- Clinically active or symptomatic viral hepatitis or chronic liver disease.
- Unstable or severe uncontrolled medical condition or any important medical or
psychiatric illness or abnormal laboratory finding that would increase the risk
to the patient associated with participation in the study.
- For Cohort M7 Only: Patients not willing to or cannot remain fasted due to a
medical condition for 2 hours before and 1 hour after dose administration.
2. Prior/Concomitant Therapy:
- Prior Anticancer Treatment:
- Systemic Anticancer Treatment: Patients must not have received
chemotherapy, targeted therapy, small molecules, antibodies,
investigational anticancer therapy, or other anticancer therapeutics
(except gonadotropin-releasing hormone analogues) within 4 weeks (or 5
half-lives, whichever is shorter) before the first dose of the study drug.
For nitrosoureas or mitomycin C, a 6-week washout is required. For prior
PD-1 or PD-L1 therapy, a washout period of at least 4 weeks is acceptable.
All toxicities from prior therapies must have resolved to Grade 1 or less,
except for endocrinopathies requiring medication, neuropathy, and
alopecia, which must have resolved to Grade 2 or less.
- EZH2 Inhibitor: Previous treatment with an EZH2 inhibitor is not allowed.
- Radiation Therapy: Patients must not have received radiation therapy
(including radiofrequency ablation) within 4 weeks before the first dose
of the study drug. However, a single fraction of radiotherapy for
palliation confined to one field is permitted within 1 week prior to Day 1
of treatment.
- Stereotactic Body Radiation Therapy: Patients must not have received this
therapy within 2 weeks before the first dose of the study drug.
- Chemoembolization or Radioembolization: Patients must not have received
these treatments within 4 weeks before the first dose of the study drug.
- Concomitant Medication:
- CYP3A4/5 Inducers or Inhibitors: Patients must not take strong CYP3A4/5
inducers or inhibitors (except enzalutamide in Cohort M8) within 7 days or
5 times the reported half-life of the CYP3A4/5 inhibitor or inducer
(whichever is longer) prior to the first dose of the study drug and for
the duration of the study.
3. Other Exclusions
- General Exclusions:
- Pregnancy and Breastfeeding: Patients who are breastfeeding, pregnant (as
confirmed by a serum β-hCG pregnancy test within 72 hours prior to the
first dose of the study drug), or planning to conceive or father children
during the trial and for 183 days after the last dose of the study drug
are excluded. Women of nonchildbearing potential (post-menopausal for more
than 1 year or surgically sterilized) do not require a serum pregnancy
test. A highly sensitive urine test can be used if a serum test is not
appropriate. Female patients with false-positive β-hCG values may be
enrolled with written consent from the Sponsor's Medical Monitor after
pregnancy has been excluded.
- Compliance: Patients who are unwilling or unable to comply with the study
protocol or requirements are excluded.
- Additional Exclusions for Cohort M6 (mCRPC) Only:
- Bone-only Disease: Patients with bone-only disease without nodal disease
and no evidence of visceral spread are excluded.
- Structurally Unstable Bone Lesions: Patients with bone lesions that are
structurally unstable and concerning for impending fracture are excluded.
- Herbal Products: Patients using herbal products that may decrease
prostate-specific antigen (PSA) levels within 4 weeks prior to Day 1 of
treatment and during the study are excluded.
- Prostate Cancer Treatments: Patients who have received the following
treatments for prostate cancer within the specified timeframes prior to
Day 1 of treatment are excluded:
1. First-generation androgen receptor antagonists (e.g., bicalutamide,
nilutamide, flutamide) within 4 weeks.
2. 5α reductase inhibitors, ketoconazole, estrogens (including
diethylstilbestrol), or progesterones within 2 weeks.
- Planned Palliative Procedures: Patients with planned palliative procedures
for alleviation of bone pain, such as radiation therapy or surgery, are
excluded.
4. Additional Exclusion Criteria for Cohort M8 (DZR123 and Enzalutamide Combination in
mCRPC) only:
- Biochemical recurrence/prostate-specific antigen (PSA)-only disease.
- Prior Enzalutamide Treatment:
- For M8 Part 1: Patients who have received prior enzalutamide.
- For M8 Part 2: Patients who have received prior enzalutamide, apalutamide,
darolutamide, or any other investigational androgen receptor pathway
inhibitor (ARPi).
- Herbal Products: Use of herbal products that may decrease PSA levels within 4
weeks prior to Day 1 of treatment and during the study.
- Planned Palliative Procedures: Planned palliative procedures for alleviation of
bone pain, such as radiation therapy or surgery.
- Investigational Agents: Treatment with any investigational agent within 4 weeks
before Day 1 of M8 Part 1 or M8 Part 2.
- Bone Marrow Irradiation: Prior irradiation to more than 25% of the bone marrow.
- Gastrointestinal Conditions: Active inflammatory gastrointestinal disease,
chronic diarrhea, known diverticular disease, or previous gastric resection or
lap band surgery. Gastroesophageal reflux disease under treatment with proton
pump inhibitors is allowed.
- Seizure History: History of seizure, loss of consciousness, or transient
ischemic attack within 12 months of study entry, or any condition that may
predispose to seizure (e.g., stroke, brain arteriovenous malformation, head
trauma, underlying brain injury).