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DZR123 (CPI-0209) in Patients with Advanced Solid Tumors and Lymphomas
EU CTIS ID: 2023-508002-20-00
What this study is testing
Phase 1 (DZR123 Monotherapy Dose Escalation): Determine maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of DZR123 as monotherapy in patients with advanced tumors Phase 2 (DZR123 Monotherapy Dose Expansion and Dose Optimization): Evaluate the antitumor activity of DZR123 as monotherapy in patients with selected advanced solid tumors and lymphomas Cohort M8 Part 1 (DZR123 and Enzalutamide Combination Dose Escalation in Patients with mCRPC): Determine the RP2D of DZR123 in combination with enzalutamide Cohort M8 Part 2 (DZR123 and Enzalutamide Combination Dose Expansion in Patients with mCRPC): Evaluate the antitumor activity of DZR123 in combination with enzalutamide.
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Adult (aged ≥ 18 years)
- Male and female patients and their partners with childbearing potential should agree to use at least one of the highly effective contraceptive methods listed in Section 6.12.1.1 while on study therapy and for 93 days after the last dose of DZR123 for male patients and male partners of female patients, and for 183 days- after the last dose of DZR123 for female patients and female partners of male patients. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Signed and dated institutional review board (IRB)/independent ethics committee (IEC) approved informed consent form (ICF) before any protocol-directed screening procedures are performed.
- P1:adults with confirmed locally advanced or metastatic tumors (solid tumors or lymphoma) who have relapsed after or progressed through standard therapy or who have a disease with no standard effective therapy P2, M1: a Confirmed, locally advanced, unresectable or metastatic UC with predominant urothelial histology b confirmed metastatic solid tumor (except OCCC, EC, and pleural or peritoneal mesothelioma) c Known ARID1A mutation d Disease progression during or following prior chemotherapy approved therapies or for which no standard therapy exists) e Measurable disease per RECIST1.1 M2:adults with Confirmed advanced OCCC b ARID1A mutation c received min.1 line of PCC and bevacizumab d Measurable disease per RECIST1.1 e Pt must have PD after receiving effective and available SoC treatment for CCOC M3:adults with Confirmed recurrent, metastatic, or unresectable EC b Known ARID1A mutation c Min.1 line of PCC in recurrent/metastatic setting d documented MSI-high or, dMMR or non-dMMR/microsatellite stable tumors should have received prior anti-PD-1 or anti-PD-L1 therapy e Brachytherapy is allowed if completed >12wks before 1st dose of study drug f Measurable disease per RECIST1.1 g Pt must have received effective and available SoC treatment for EC M4: adults with lymphoma: a Confirmed PTCL or DLBCL with following criteria: PTCL: Documented refractory, relapsed, or PD after min.1 prior line of systemic therapy. Must have min.1 prior line of systemic therapy for PTCL o Pts must be considered HCT ineligible during screening due to disease status (active disease), comorbidities, other factors o In PTCL, pts with ALCL must have prior brentuximab vedotin treatment DLBCL: Relapsed/refractory disease following 2 or more prior lines of SoC therapy Not considered candidates to receive CAR-T or ASCT as assessed by the treating investigator For pts with past ASCT or CAR-T treatment, min.90 days must have elapsed since start of the procedure. For all other pts, min.8 wks must have elapsed since most recent systemic anti-DLBCL therapy b Min.1 bi-dimensionally measurable lesion on imaging scan defined as >1. 5cm in its longest dimension M5: a Pleural or peritoneal relapsed/refractory mesothelioma b Must have progressed on or after min.1 prior line of active therapy c Have measurable disease for pleural mesothelioma (modified RECIST1.1) or for peritoneal mesothelioma (RECIST1.1) d. Known BAP1 loss per IHC or NGS testing M6:adults with mCRPC: a Have measurable soft-tissue disease with CT scan as defined by PCWG3 criteria b Documented metastatic disease c Progression while on prior therapies d Baseline testosterone levels must be ≤50 ng/dL (≤2.0 nM), surgical or ongoing medical castration must be maintained throughout the study M7: a confirmed recurrent, metastatic, or unresectable EC b Known ARID1A wildtype status and up to 5 pts with known TP53 alterations (both confirmed by NGS testing) c Received max. 2 prior lines of systemic therapy for metastatic/recurrent EC incl min. 1 line platinum-based regimen and anti-PD-1 or anti-PD-L1 agent alone or in combination unless these are contraindicated or are not locally accessible d Measurable disease per RECIST 1.1 M8: pts with prostate cancer with metastatic disease documented by bone and/or measurable soft tissue/visceral disease as per PCWG3 criteria, M8 Part 1 only: must have received min.1 ARPi (excl. enzalutamide) treatment in mCRPC or HSPC disease stage. M8 Part 2 only: must have received abiratoerone treatment in mCRPC or HSPC disease stage. For M8 Part 1 only: max 1 previous regimen of taxane-based chemotherapy in mCRPC or HSPC setting. For M8 Part 2 only: max 1 previous regimen of taxane-based chemotherapy in HSPC. For M8 Part 1 and M8 Part 2: pts with prostate cancer progression (per PCWG3) and ongoing ADT with a GnRH analogue, antagonist or bilateral orchiectomy, have baseline testosterone levels ≤ 50 ng/dL (≤ 2.0 nM), have surgical or ongoing medical castration
- 2. Have a life expectancy of ≥ 12 weeks
- Provide a baseline archival tumor sample (Phase 1); for Phase 2, provide a fresh or archival tumor biopsy at baseline, except as noted for Cohort M4 and Cohort M6. Refer to Section 6.2.11 and Section 6.2.12.
You likely can't join if
- Previous solid organ or allogeneic HCT.
- Have a history of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years. Patients with a history of T-cell lymphoblastic lymphoma or T-cell lymphoblastic leukemia are not eligible.
- Have current known active or chronic infection with HIV, hepatitis B, or hepatitis C. Screening of patients with serologic testing for these viruses is not required. However, patients who have a past history of viral hepatitis or in whom there is a current suspicion of viral hepatitis should have serologic testing for hepatitis B and hepatitis C performed to determine whether there is any current evidence for ongoing infection with these viruses. Patients considered to be at risk for HIV infection should have HIV testing performed.
- 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 the dose administration.
- For Cohort M8 only: - Biochemical recurrence/prostate-PSA-only disease - ONLY FOR M8 PART 1: Patients who received prior enzalutamide. ONLY FOR M8 PART 2: Patients who received prior enzalutamide, apalutamide, darolutamide or any other investigational ARPi. - Herbal products that may decrease PSA levels within 4 weeks prior to Day 1 of treatment and while on study - Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery. - Treatment with any investigational agent within 4 weeks before Day 1 of M8 Part 1 or M8 Part 2. - Prior irradiation to >25% of the bone marrow. - 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. - 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).
- Clinically active or symptomatic viral hepatitis or chronic liver disease.
See the full eligibility criteria
Who can join
- 1. Adult (aged ≥ 18 years)
- Male and female patients and their partners with childbearing potential should agree to use at least one of the highly effective contraceptive methods listed in Section 6.12.1.1 while on study therapy and for 93 days after the last dose of DZR123 for male patients and male partners of female patients, and for 183 days- after the last dose of DZR123 for female patients and female partners of male patients. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Signed and dated institutional review board (IRB)/independent ethics committee (IEC) approved informed consent form (ICF) before any protocol-directed screening procedures are performed.
- P1:adults with confirmed locally advanced or metastatic tumors (solid tumors or lymphoma) who have relapsed after or progressed through standard therapy or who have a disease with no standard effective therapy P2, M1: a Confirmed, locally advanced, unresectable or metastatic UC with predominant urothelial histology b confirmed metastatic solid tumor (except OCCC, EC, and pleural or peritoneal mesothelioma) c Known ARID1A mutation d Disease progression during or following prior chemotherapy approved therapies or for which no standard therapy exists) e Measurable disease per RECIST1.1 M2:adults with Confirmed advanced OCCC b ARID1A mutation c received min.1 line of PCC and bevacizumab d Measurable disease per RECIST1.1 e Pt must have PD after receiving effective and available SoC treatment for CCOC M3:adults with Confirmed recurrent, metastatic, or unresectable EC b Known ARID1A mutation c Min.1 line of PCC in recurrent/metastatic setting d documented MSI-high or, dMMR or non-dMMR/microsatellite stable tumors should have received prior anti-PD-1 or anti-PD-L1 therapy e Brachytherapy is allowed if completed >12wks before 1st dose of study drug f Measurable disease per RECIST1.1 g Pt must have received effective and available SoC treatment for EC M4: adults with lymphoma: a Confirmed PTCL or DLBCL with following criteria: PTCL: Documented refractory, relapsed, or PD after min.1 prior line of systemic therapy. Must have min.1 prior line of systemic therapy for PTCL o Pts must be considered HCT ineligible during screening due to disease status (active disease), comorbidities, other factors o In PTCL, pts with ALCL must have prior brentuximab vedotin treatment DLBCL: Relapsed/refractory disease following 2 or more prior lines of SoC therapy Not considered candidates to receive CAR-T or ASCT as assessed by the treating investigator For pts with past ASCT or CAR-T treatment, min.90 days must have elapsed since start of the procedure. For all other pts, min.8 wks must have elapsed since most recent systemic anti-DLBCL therapy b Min.1 bi-dimensionally measurable lesion on imaging scan defined as >1. 5cm in its longest dimension M5: a Pleural or peritoneal relapsed/refractory mesothelioma b Must have progressed on or after min.1 prior line of active therapy c Have measurable disease for pleural mesothelioma (modified RECIST1.1) or for peritoneal mesothelioma (RECIST1.1) d. Known BAP1 loss per IHC or NGS testing M6:adults with mCRPC: a Have measurable soft-tissue disease with CT scan as defined by PCWG3 criteria b Documented metastatic disease c Progression while on prior therapies d Baseline testosterone levels must be ≤50 ng/dL (≤2.0 nM), surgical or ongoing medical castration must be maintained throughout the study M7: a confirmed recurrent, metastatic, or unresectable EC b Known ARID1A wildtype status and up to 5 pts with known TP53 alterations (both confirmed by NGS testing) c Received max. 2 prior lines of systemic therapy for metastatic/recurrent EC incl min. 1 line platinum-based regimen and anti-PD-1 or anti-PD-L1 agent alone or in combination unless these are contraindicated or are not locally accessible d Measurable disease per RECIST 1.1 M8: pts with prostate cancer with metastatic disease documented by bone and/or measurable soft tissue/visceral disease as per PCWG3 criteria, M8 Part 1 only: must have received min.1 ARPi (excl. enzalutamide) treatment in mCRPC or HSPC disease stage. M8 Part 2 only: must have received abiratoerone treatment in mCRPC or HSPC disease stage. For M8 Part 1 only: max 1 previous regimen of taxane-based chemotherapy in mCRPC or HSPC setting. For M8 Part 2 only: max 1 previous regimen of taxane-based chemotherapy in HSPC. For M8 Part 1 and M8 Part 2: pts with prostate cancer progression (per PCWG3) and ongoing ADT with a GnRH analogue, antagonist or bilateral orchiectomy, have baseline testosterone levels ≤ 50 ng/dL (≤ 2.0 nM), have surgical or ongoing medical castration
- 2. Have a life expectancy of ≥ 12 weeks
- Provide a baseline archival tumor sample (Phase 1); for Phase 2, provide a fresh or archival tumor biopsy at baseline, except as noted for Cohort M4 and Cohort M6. Refer to Section 6.2.11 and Section 6.2.12.
- Must be willing to provide blood and tumor samples for central biomarker testing
- Recovered to baseline or Grade ≤ 1 severity from toxicity related to prior treatments, unless AEs are clinically non-significant and/or stable on supportive therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Adequate bone marrow function defined by the following hematological parameters: +Solid tumor patients: - absolute neutrophil count (ANC) of ≥ 1.5 × 10^9/L, without growth factor support (filgrastim or pegfilgrastim) for at least 14 days - platelet count of ≥ 100×10^9/L - hemoglobin of ≥ 9.0 g/dL (with or without transfusion) + Lymphoma patients with documented bone marrow involvement: - ANC ≥ 0.75 × 10^9/L, without growth factor support (filgrastim or pegfilgrastim) for at least 14 days - platelet count of ≥ 75 x 10^9/L, without platelet transfusion for at least 14 days - hemoglobin ≥ 9.0 g/dL (with or without transfusion)
- Adequate renal function defined as creatinine clearance > 30 mL/min for patients with creatinine levels above institutional normal as determined by Cockcroft-Gault equation OR serum creatinine ≤ 1.5 × the upper limit of normal (ULN)
- Adequate hepatic function defined as serum total bilirubin ≤ 1.5 × ULN, AND aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases); for patients who have known Gilbert’s disease with total bilirubin < 3 × ULN may be eligible provided that the treating physician does not consider it clinically significant.
What rules you out
- Previous solid organ or allogeneic HCT.
- Have a history of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years. Patients with a history of T-cell lymphoblastic lymphoma or T-cell lymphoblastic leukemia are not eligible.
- Have current known active or chronic infection with HIV, hepatitis B, or hepatitis C. Screening of patients with serologic testing for these viruses is not required. However, patients who have a past history of viral hepatitis or in whom there is a current suspicion of viral hepatitis should have serologic testing for hepatitis B and hepatitis C performed to determine whether there is any current evidence for ongoing infection with these viruses. Patients considered to be at risk for HIV infection should have HIV testing performed.
- 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 the dose administration.
- For Cohort M8 only: - Biochemical recurrence/prostate-PSA-only disease - ONLY FOR M8 PART 1: Patients who received prior enzalutamide. ONLY FOR M8 PART 2: Patients who received prior enzalutamide, apalutamide, darolutamide or any other investigational ARPi. - Herbal products that may decrease PSA levels within 4 weeks prior to Day 1 of treatment and while on study - Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery. - Treatment with any investigational agent within 4 weeks before Day 1 of M8 Part 1 or M8 Part 2. - Prior irradiation to >25% of the bone marrow. - 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. - 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).
- 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, in the Investigator’s judgment, increase the risk to the patient associated with his or her participation in the study.
- Known symptomatic untreated brain metastases. Patients with CNS metastases must have stable neurologic status following local therapy for at least 4 weeks on stable or decreasing dose of steroid ≤ 10 mg daily prednisone (or equivalent). Patients in the M4 lymphoma cohort will not be eligible if they have known CNS involvement by lymphoma.
- Clinically significant cardiovascular disease including: a. Myocardial infarction/stroke within 3 months prior (6 months for M8 cohort) to Day 1 of treatment. b. Unstable angina within 3 months (6 months for M8 cohort) prior to Day 1 of treatment. c. Congestive heart failure or cardiomyopathy with New York Heart Association (NYHA; see APPENDIX 3) Class 3 or 4. d. History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes). e. Uncontrolled hypertension (as defined per institutional standards) despite 2 concomitant antihypertensive therapies. f. For Cohorts M1-M6: QT interval corrected by the Fridericia correction formula (QTcF) ≥ 480 msec on the Screening ECG. For Cohort 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, ie, ulcerative colitis, malabsorption syndrome, refractory nausea and vomiting, biliary shunt, significant bowel resection, or any other condition that may significantly interfere with absorption of the study medication by Investigator’s assessment.
- Uncontrolled active infection requiring intravenous antibiotic, antiviral, or antifungal medications within 14 days before the first dose of study drug. Infections (eg, urinary tract infection) controlled 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 pneumonitis or interstitial lung disease.
The study team makes the final eligibility decision.
Where it's taking place
- United States
- United Kingdom
- Korea, Republic of
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; United Kingdom; Korea, Republic of. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.