Urothelial Cancer
Conditions
Keywords
durvalumab, MEDI4736, anti-PD-L1
Brief summary
This is an open label, multi-institutional, single arm study of a phase Ib study, followed by a phase II study of durvalumab with radiation therapy (RT) in patients with urothelial cancer (UC). No randomization or blinding is involved.
Detailed description
OUTLINE: This is a multi-center study. The phase Ib study will evaluate the safety of combining durvalumab with RT followed by adjuvant durvalumab. The phase II study will estimate the Progression Free Survival (PFS) and Disease Control Rate (DCR) with durvalumab plus RT followed by single agent durvalumab for patients with UC of bladder. PHASE Ib INVESTIGATIONAL TREATMENT: Cohort 1 will consist of up to 6 patients who will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will be started on day 1; RT will be started on day 1 or 2. Three patients will be enrolled initially. If 2 or more patients (out of 3) experience dose-limiting toxicity (DLT), the combined treatment will be considered unsafe. Otherwise, an additional 3 patients will be treated at the same dose. If 0 or 1 patient experience DLT, the dose of durvalumab will be deemed safe for phase 2 part of the study. If, however, 2 or more patients (out of 6) experience DLT, the combined treatment will be considered unsafe. Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab treatment will be started 3-4 weeks post completion of durvalumab and RT. PHASE II INVESTIGATIONAL TREATMENT: Subjects will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will start on Day 1. RT to start on Day 1 or 2. Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab monotherapy will be started 3-4 weeks post completion of durvalumab and RT. Life expectancy of \>6 months per treating physician. Adequate organ and marrow function as defined below: 1. Hemoglobin ≥ 9.0 g/dL 2. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (\> 1500 per mm\^3) 3. Platelet count ≥ 100 x 10\^9/L (\>100,000 per mm\^3) 4. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. 5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN. 6. Serum creatinine CL\>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
Interventions
DRUGdurvalumab
1500 mg Q4 weekly
RADIATIONRadiation Therapy
64.8 Gy, 36 daily fractions on weekdays over about 7 weeks
Sponsors
AstraZeneca
Monika Joshi, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase Ib subjects must meet the following inclusion criteria: * Locally advanced urothelial cancer of bladder with any of the following: 1. T3-4, N0-2 M0, OR Tx N1-2 M0 OR T2 N1-2 M0: Treatment naïve, unresectable, OR medically unfit for surgery, OR cisplatin ineligible. T3 N0 M0 patients can be included if they are cisplatin ineligible. 2. Patients who have T3-4, N0-2 M0 OR Tx N1-2 M0 OR T2 N1-2 M0 post-neoadjuvant chemotherapy who become unresectable OR medically unfit for surgery. Phase II subjects must meet the following inclusion criteria: * Locally advanced urothelial cancer of bladder with any of the following: 1. T3-4, N0-2 M0 OR Tx N1-2 M0 OR T2 N1-2 M0: Treatment naïve, unresectable, OR medically unfit for surgery OR cisplatin ineligible. T3 N0 M0 patients can be included if they are cisplatin ineligible. 2. T3-4, N0-1 M0 OR Tx N1-2 M0 OR T2 N1-2 M0 patients post-neoadjuvant chemotherapy who become unresectable OR medically unfit for surgery. * T2, N0, M0 who are ineligible to get cisplatin based chemotherapy. All subjects: * Written informed consent and HIPAA authorization for personal health information, obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Life expectancy of \>6 months per treating physician. * Subjects must have archival tissue available from previous TURBT (preferred) or lymph node core biopsy within 8 weeks of treatment or be assessed by the treating urologist to undergo maximal TURBT. The extent of TURBT may vary for each patient and will be determined by the treating urologist. Further, the treating urologist will decide if performing the TURBT is clinically appropriate. If the potential subject does not have tumor amenable to biopsy, there is insufficient tissue for PD-L1 testing or is not clinically appropriate for TURBT, enrollment must be discussed with the sponsor-investigator on a case by case basis. * Histologically proven urothelial carcinoma of bladder with predominant transitional cell component. Adenocarcinoma, squamous cell differentiation, or other atypical histology (such as plasmacytoid or sarcomotoid) of the bladder will be allowed on the study, provided they form \<50% of the histology * Females of childbearing potential must have a negative urine and serum pregnancy test within 3 days of study registration. NOTE: Female subjects are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are ≥60 years old and naturally postmenopausal for at least 12 consecutive months. * Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion criteria
* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). * Participation in another clinical study with an investigational product within 2 weeks prior to registration. * Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab. * Previous systemic immunotherapy. Previous use of intravesical BCG is acceptable. * History of another primary malignancy except for: 1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence. However adequately treated prostate cancer \>3 years ago with no significant change in PSA for past 6 months can be included. Patients with a history of prostate cancer must not have any definitive radiation therapy to prostate area. 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3. Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ. * Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within14 days prior to the first dose of study drug (14 days prior to the first dose of study drug for subjects who have received prior TKIs \[e.g., erlotinib, gefitinib and crizotinib\] and within 6 weeks for nitrosourea or mitomycin C). * Mean QT interval corrected for heart rate (QTc) ≥470 ms on electrocardiogram (ECG) using Frediricia's Correction. * Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. * Any unresolved toxicity (\>CTCAE grade 2) from previous anti-cancer therapy. (Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy). * Any prior Grade ≥3 Immune-mediated adverse event (imAE) while receiving any previous immunotherapy agent, or any unresolved imAE \>Grade 1. * Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Patients with h/o completely resolved childhood asthma or atopy will not be excluded. Patients with well-controlled hypothyroidism on thyroxine replacement will be eligible as well. * Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). * History of and/or confirmed pneumonitis. * History of primary immunodeficiency. * History of allogeneic organ transplant. * History of hypersensitivity to durvalumab or any excipient. * History of hypersensitivity to the combination or radiation therapy. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. * Known history of previous clinical diagnosis of tuberculosis. * Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of starting treatment with durvalumab. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. * Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control. For this study male or female patients of reproductive potential need to employ two highly effective and acceptable forms of contraception throughout their participation in the study and for 90 days after last dose of study drug * Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results. * Brain metastases or history of leptomeningeal carcinomatosis. * Subjects with uncontrolled seizures. * Previous definitive radiation to pelvic area.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Safety Assessment - Evaluation of DLT (Dose Limiting Toxicity) Rate | Begin W1 and every 2 chemotherapy cycles (2 weeks) thereafter, for up to 2 years or until unacceptable toxicity. | To assess the safety of combining durvalumab with RT in that DLT rate is lower than than 33% based on CTCAEv4.0 |
| All Phases: Progression Free Survival Rate at 1 Year | From C1D1 to Progression or until death for 1 year | Progression free survival rate at one year is defined as the probability that a patient remains free of progression of disease (SD+CR+PR) by modified RECIST 1.1 and cystoscopy at 1 year from the start of durvalumab treatment, D1 of durvaRT. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Phase II: Disease Control Rate to Concurrent durvaRT Followed by Durvalumab | From C1D1 until death or up to a maximum of 39 months. | The number of all subjects is reported with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to modified RECIST 1.1 and cystoscopy, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease(SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started;Disease Control Rate (DCR) = CR + PR+SD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Phases: DCR Post Completion of Concurrent durvaRT | From C1D1 until death or up to a maximum of 39 months | We will be determining the disease control rate, defined as percentage of patients achieving CR, PR, SD post completion of concurrent durvaRT. This will give us some preliminary evidence for efficacy of durvaRT combination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease(SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started;Disease Control Rate (DCR) = CR + PR+SD |
| All Phases: Overall Survival | From C1D1 until death or 39 months. | Estimate the overall survival (OS), defined as time from start of treatment, D1, to the date of death due to any cause. OS is defined, as time from start of treatment to the date of death due to any cause, or to the date of censoring at the last time the subject was known to be alive in intention-to-treat population. OS is one of the secondary objectives of this study. This is an immunotherapy based clinical trial and it is prudent to determine the OS to reflect the long-term benefit from this therapeutic approach. |
| All Phases : Median Progression Free Survival (PFS) Time | From C1D1 to PD or until death or up to a maximum of 37 months. | Median progression free survival will be determined for all subjects. |
| Phase II: Complete Remission | From C1D1 until CR or death or up to a maximum of 39 months. | Estimate the rate of CR is one of the secondary objectives for phase II part of this study. This will help us determine the actual effectiveness of durvaRT approach. CR will be determined with the help of imaging and cystoscopy post completion of durvaRT per modified RECIST 1.1. Number of subjects reporting CR will be reported here. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm Ib: Safety Run In Phase Ib Subjects will receive durvalumab 1500mg Q4 weekly with RT to gross disease over 36 fractions. Durvalumab will start on Day 1. RT to start on Day 1 or 2. Subjects will receive adjuvant durvalumab monotherapy Q4 week, up to 12 months. Durvalumab monotherapy to start 4 weeks post completion of durvalumab and RT.
durvalumab: 1500 mg Q4 weekly
Radiation Therapy: 64.8 Gy, 36 daily fractions on weekdays over about 7 weeks | 6 |
| Arm II: Investigational Treatment Phase II Subjects will receive durvalumab 1500mg Q4 weekly with RT to gross disease over 36 fractions. Durvalumab will start on Day 1. RT to start on Day 1 or 2. Subjects will receive adjuvant durvalumab monotherapy Q4 week, up to 12 months. Adjuvant durvalumab monotherapy to start 4 weeks post completion of durvalumab and RT.
durvalumab: 1500 mg Q4 weekly | 20 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow up | Death | 4 | 8 |
| Follow up | Refused to Follow up | 0 | 2 |
| Follow up | Study terminated | 0 | 6 |
| Follow up | Symptomatic deterioration | 0 | 1 |
| Study Treatment | AE/Side Effects/Complications | 1 | 5 |
| Study Treatment | Disease Progression | 2 | 4 |
| Study Treatment | Patient withdrawal After Therapy Start | 1 | 4 |
Baseline characteristics
| Characteristic | Arm II: Investigational Treatment Phase II | Arm Ib: Safety Run In Phase Ib | Total |
|---|---|---|---|
| Age, Continuous | 76.6 years STANDARD_DEVIATION 7.44 | 69.5 years STANDARD_DEVIATION 14.05 | 75 years STANDARD_DEVIATION 9.5 |
| Cisplatin ineligible Subject is cisplatin ineligible at screening | 19 Participants | 4 Participants | 23 Participants |
| Cisplatin ineligible Subject is not cisplatin ineligible at screening | 1 Participants | 2 Participants | 3 Participants |
| ECOG status 0-1 | 14 Participants | 5 Participants | 19 Participants |
| ECOG status 2 | 6 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Non-Hispanic | 18 Participants | 5 Participants | 23 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 14 Participants | 5 Participants | 19 Participants |
| Tumor Node Metastasis (TNM) stage at screening T2N0M0 | 10 Participants | 0 Participants | 10 Participants |
| Tumor Node Metastasis (TNM) stage at screening T2N1M0 | 2 Participants | 1 Participants | 3 Participants |
| Tumor Node Metastasis (TNM) stage at screening T2N2M0 | 1 Participants | 0 Participants | 1 Participants |
| Tumor Node Metastasis (TNM) stage at screening T3N0M0 | 5 Participants | 1 Participants | 6 Participants |
| Tumor Node Metastasis (TNM) stage at screening T3N2M0 | 1 Participants | 1 Participants | 2 Participants |
| Tumor Node Metastasis (TNM) stage at screening T4N0M0 | 0 Participants | 1 Participants | 1 Participants |
| Tumor Node Metastasis (TNM) stage at screening T4N1M0 | 0 Participants | 1 Participants | 1 Participants |
| Tumor Node Metastasis (TNM) stage at screening T4N2M0 | 0 Participants | 1 Participants | 1 Participants |
| Tumor Node Metastasis (TNM) stage at screening T4NXMX | 1 Participants | 0 Participants | 1 Participants |
| Unfit for surgery Subject is medically unfit for surgery at screening | 11 Participants | 2 Participants | 13 Participants |
| Unfit for surgery Subject is not medically unfit for surgery at screening | 9 Participants | 4 Participants | 13 Participants |
| Unresectable Subject's tumor is not unresectable at screening. | 14 Participants | 3 Participants | 17 Participants |
| Unresectable Subject's tumor is unresectable at screening. | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 6 | 8 / 20 |
| other Total, other adverse events | 6 / 6 | 20 / 20 |
| serious Total, serious adverse events | 4 / 6 | 8 / 20 |
Outcome results
Primary
All Phases: Progression Free Survival Rate at 1 Year
Progression free survival rate at one year is defined as the probability that a patient remains free of progression of disease (SD+CR+PR) by modified RECIST 1.1 and cystoscopy at 1 year from the start of durvalumab treatment, D1 of durvaRT. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From C1D1 to Progression or until death for 1 year
Population: All Phase Ib and Phase II subjects were analyzed together.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm Ib: Safety Run In Phase Ib | All Phases: Progression Free Survival Rate at 1 Year | 71.5 percentage of participants |
Primary
Phase Ib: Safety Assessment - Evaluation of DLT (Dose Limiting Toxicity) Rate
To assess the safety of combining durvalumab with RT in that DLT rate is lower than than 33% based on CTCAEv4.0
Time frame: Begin W1 and every 2 chemotherapy cycles (2 weeks) thereafter, for up to 2 years or until unacceptable toxicity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm Ib: Safety Run In Phase Ib | Phase Ib: Safety Assessment - Evaluation of DLT (Dose Limiting Toxicity) Rate | 0 Participants |
Primary
Phase II: Disease Control Rate to Concurrent durvaRT Followed by Durvalumab
The number of all subjects is reported with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to modified RECIST 1.1 and cystoscopy, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease(SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started;Disease Control Rate (DCR) = CR + PR+SD
Time frame: From C1D1 until death or up to a maximum of 39 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm Ib: Safety Run In Phase Ib | Phase II: Disease Control Rate to Concurrent durvaRT Followed by Durvalumab | 13 Participants |
Secondary
All Phases: DCR Post Completion of Concurrent durvaRT
We will be determining the disease control rate, defined as percentage of patients achieving CR, PR, SD post completion of concurrent durvaRT. This will give us some preliminary evidence for efficacy of durvaRT combination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease(SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started;Disease Control Rate (DCR) = CR + PR+SD
Time frame: From C1D1 until death or up to a maximum of 39 months
Population: Phase Ib and Phase II subjects were analyzed together.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm Ib: Safety Run In Phase Ib | All Phases: DCR Post Completion of Concurrent durvaRT | 72.7 percentage of participants |
Secondary
All Phases : Median Progression Free Survival (PFS) Time
Median progression free survival will be determined for all subjects.
Time frame: From C1D1 to PD or until death or up to a maximum of 37 months.
Population: Phase Ib and Phase II subjects were analyzed together
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm Ib: Safety Run In Phase Ib | All Phases : Median Progression Free Survival (PFS) Time | 21.8 months |
Secondary
All Phases: Overall Survival
Estimate the overall survival (OS), defined as time from start of treatment, D1, to the date of death due to any cause. OS is defined, as time from start of treatment to the date of death due to any cause, or to the date of censoring at the last time the subject was known to be alive in intention-to-treat population. OS is one of the secondary objectives of this study. This is an immunotherapy based clinical trial and it is prudent to determine the OS to reflect the long-term benefit from this therapeutic approach.
Time frame: From C1D1 until death or 39 months.
Population: Phase Ib and Phase II subjects were analyzed together.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm Ib: Safety Run In Phase Ib | All Phases: Overall Survival | 30.8 months |
Secondary
Phase II: Complete Remission
Estimate the rate of CR is one of the secondary objectives for phase II part of this study. This will help us determine the actual effectiveness of durvaRT approach. CR will be determined with the help of imaging and cystoscopy post completion of durvaRT per modified RECIST 1.1. Number of subjects reporting CR will be reported here. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions.
Time frame: From C1D1 until CR or death or up to a maximum of 39 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm Ib: Safety Run In Phase Ib | Phase II: Complete Remission | 17 Participants |