Adenocarcinoma, Gastrointestinal Neoplasms
Conditions
Keywords
Secondary
Brief summary
The Phase 1b study is an open-label, multicenter dose escalation study designed to assess the safety, tolerability, immunogenicity and recommended phase 2 dose (RP2D) of IMU-131. The RP2D will be evaluated in the dose expansion Phase 2 study. The Phase 2 study is a randomized, open label comparison of IMU-131 plus standard of care chemotherapy versus standard of care chemotherapy alone.
Interventions
BIOLOGICALIMU-131
IMU-131 vaccine is a P467-CRM197 peptide antigen in PBS buffer and Montanide ISA 51 Sterile adjuvant
DRUGCisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.
Chemotherapy will consist of: cisplatin by intravenous administration at 80 mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 1 to 4 of each cycle) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle), or (in Phase 2 only) oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each cycle and capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle).
Sponsors
Imugene Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Partially blinded - blinded central review of progression.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines; 2. Age ≥ 20 years old; 3. Life expectancy of at least 12 weeks; 4. Phase 1b: No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 6 months prior to Day 0; Phase 2: No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 3 months prior to Day 0; 5. Metastatic gastric or GEJ adenocarcinoma, or locally advanced disease not amenable to surgical resection; 6. HER2/neu overexpression (3+ by immunohistochemistry (IHC) or if IHC 2+ confirmed by fluorescent in situ hybridization \[FISH\] or chromogenic in situ hybridization \[CISH\]). Patients with IHC 2+ expression without confirmation of overexpression by fluorescent in situ hybridization \[FISH\] or chromogenic in situ hybridization \[CISH\]) may be included in Phase 1b with agreement of Imugene Limited; 7. Phase 1b: ECOG performance status 0-1; Phase 2: ECOG performance status 0-2; 8. At least one measurable lesion as defined by RECIST 1.1 criteria. Patients with non-measurable lesions may be included in Phase1b with agreement of Imugene Limited; 9. Adequate left ventricular ejection function at baseline, defined as LVEF \> 50% by echocardiogram or MUGA scan (Multi Gated Acquisition Scan); 10. Adequate hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL; 11. Adequate liver function evidenced by bilirubin ≤ 1.5 x laboratory upper limit of normal \[ULN\], and ALT and AST ≤ 3 x laboratory ULN if no liver involvement or ALT and AST ≤ 5 times laboratory ULN with liver involvement; 12. Adequate renal function (creatinine ≤ 1.5 x laboratory ULN); 13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 14. Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment (see section 4.3 for details). A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
Exclusion criteria
1. Previous treatment with trastuzumab or any other HER2/neu targeting antibody or agent; 2. Continuous systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease; 3. Prior organ transplant; 4. Phase 1b: Patient not considered a candidate for 5-FU, capecitabine, or cisplatin chemotherapy; Phase 2: Patient not considered a candidate for 5-FU, capecitabine, cisplatin or oxaliplatin chemotherapy; 5. History of documented congestive heart failure; angina pectoris requiring antianginal medication; evidence of transmural infarction on ECG; poorly controlled hypertension; clinically significant valvular heart disease; high risk uncontrolled arrhythmias; or New York Heart Association (NYHA) class II heart disease; 6. If on warfarin (Coumadin®) or other vitamin K antagonists; 7. Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin; 8. Peripheral neuropathy or hearing loss of NCI CTCAE Grade \> 2; 9. History of uncontrolled seizures, central nervous disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent, participation in the study, or adversely affecting compliance to study drugs; 10. Active infection requiring IV antibiotics; 11. Positive for human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active hepatitis B (HBsAg reactive) or active hepatitis C (HCV ribonucleic acid \[RNA\] qualitative) infection; 12. Pregnant or lactating females; 13. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry; 14. Has received a live-virus vaccination within 4 weeks of first study vaccination. Seasonal flu vaccines that do not contain live virus are permitted; 15. Current or recent (within 4 weeks of first IMU-131 vaccination) treatment with another investigational drug or participation in another investigational study. 16. Phase 2: Patients with a known diphtheria toxoid hypersensitivity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Number of Participants With Adverse Events (AEs) | Up to approximately 7 months | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section. |
| Phase 2: Overall Survival (OS) | Up to approximately 30 months | OS was measured from date of randomization to date of death due to any cause. |
| Phase 2 Extension: Number of Participants With AEs | From date of first dose to date of last dose plus 30 days (Up to 24 months) | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 and Phase 2 Extension: Objective Response Rate (ORR) | Up to approximately 30 months | ORR was defined as the proportion of participants with a BOR of CR or PR according RECIST 1.1 after randomization/enrollment date. |
| Phase 2 and Phase 2 Extension: Duration of Response (DOR) | Up to approximately 30 months | DOR was defined as the time from the earliest date when a tumor response of CR or PR was observed until the date of first occurrence of disease progression which assessed by the blinded central reviewer or death (due to any reason). |
| Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS) | Up to approximately 30 months | PFS was measured from randomization to date of earliest progressive disease (PD) based on blinded central review according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or to date of death from any cause. |
| Phase 2 Extension: OS | Up to 24 months | OS was measured from date of randomization to date of death due to any cause. |
| Phase 2 and Phase 2 Extension: Percentage Change From Baseline in Tumor Size | Baseline up to approximately 30 months | Change in tumor size (CTS) was measured as the sum of diameters based on blinded central review according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1). |
| Phase 2 and Phase 2 Extension: Time to Progression (TTP) | Up to approximately 30 months | TTP was measured from randomization to date of earliest PD based on blinded central review according to RECIST 1.1 criteria. |
| Phase 2 and Phase 2 Extension: Disease Control Rate (DCR) | Up to approximately 30 months | DCR was defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), or stable disease according to RECIST 1.1 after randomization/enrollment date. |
Countries
Georgia, India, Moldova, Serbia, Taiwan, Thailand, Ukraine
Participant flow
Pre-assignment details
A total of 64 participants were enrolled in the study. Phase 1b, Phase 2, and Phase 2 extension parts enrolled separate participant populations.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy Participants received IMU-131 in IM injections at a single dose level of 10 μg on Days 0, 14, 35, 98 and then every 12 weeks accompanied by chemotherapy every 21 days starting from Day 14. Chemotherapy included IV cisplatin and either 5-FU infusion or oral capecitabine. | 3 |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy Participants received IMU-131 in IM injections at a single dose level of 30 μg on Days 0, 14, 35, 98 and then every 12 weeks accompanied by chemotherapy every 21 days starting from Day 14. Chemotherapy included IV cisplatin and either 5-FU infusion or oral capecitabine | 6 |
| Phase 1b: 50 μg IMU-131 Plus Chemotherapy Participants received IMU-131 in IM injections at a single dose level of 50 μg on Days 0, 14, 35, 98 and then every 12 weeks accompanied by chemotherapy every 21 days starting from Day 14. Chemotherapy included IV cisplatin and either 5-FU infusion or oral capecitabine. | 5 |
| Phase 2: IMU-131 Plus Chemotherapy Participants received IMU-131 in IM injections at dose level of 50 μg on Days 0, 14, 35, 77, and 140, then every 63 days until disease progression accompanied by chemotherapy every 21 days for up to 6 cycles starting from Day 14. Chemotherapy included one of the following treatments:
* IV cisplatin and either 5-FU infusion or oral capecitabine.
* IV oxaliplatin and oral capecitabine. | 19 |
| Phase 2: Chemotherapy Only Participants received chemotherapy every 21 days for up to 6 cycles starting from Day 14. Chemotherapy included one of the following treatments:
* IV cisplatin and either 5-FU infusion or oral capecitabine.
* IV oxaliplatin and oral capecitabine. | 17 |
| Phase 2 Extension: IMU-131 100 μg Participants received IMU-131 in IM injections at dose level of 100 μg on Days 0, 14, and 35, then every 63 days until disease progression accompanied by chemotherapy every 21 days for up to 6 cycles starting from Day 0. Chemotherapy included one of the following treatments:
* IV cisplatin and either 5-FU infusion or oral capecitabine.
* IV oxaliplatin and oral capecitabine. | 7 |
| Phase 2 Extension: IMU-131 200 μg Participants received IMU-131 in IM injections at dose level of 200 μg on Days 0, 14, and 35, then every 63 days until disease progression accompanied by chemotherapy every 21 days for up to 6 cycles starting from Day 0. Chemotherapy included one of the following treatments:
* IV cisplatin and either 5-FU infusion or oral capecitabine.
* IV oxaliplatin and oral capecitabine. | 7 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Phase 1b | Death | 1 | 2 | 1 | 0 | 0 | 0 | 0 |
| Phase 1b | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Phase 1b | Progressive Disease | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
| Phase 1b | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Phase 2 | Death | 0 | 0 | 0 | 17 | 17 | 0 | 0 |
| Phase 2 | Other | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Phase 2 | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Phase 2 Extension | Death | 0 | 0 | 0 | 0 | 0 | 5 | 6 |
| Phase 2 Extension | Other reasons | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 1b: 50 μg IMU-131 Plus Chemotherapy | Total | Phase 2: IMU-131 Plus Chemotherapy | Phase 2: Chemotherapy Only | Phase 2 Extension: IMU-131 100 μg | Phase 2 Extension: IMU-131 200 μg |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous Phase 1b | 51.0 years STANDARD_DEVIATION 24.6 | 60.3 years STANDARD_DEVIATION 9.8 | 57.4 years STANDARD_DEVIATION 21 | 57.3 years STANDARD_DEVIATION 16.7 | — | — | — | — |
| Age, Continuous Phase 2 | — | — | — | 64.5 years STANDARD_DEVIATION 9.28 | 64.4 years STANDARD_DEVIATION 8.53 | 64.6 years STANDARD_DEVIATION 10.31 | — | — |
| Age, Continuous Phase 2 Extension | — | — | — | 65.9 years STANDARD_DEVIATION 12.71 | — | — | 62.1 years STANDARD_DEVIATION 15.19 | 69.7 years STANDARD_DEVIATION 9.25 |
| Ethnicity (NIH/OMB) Phase 1b Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Phase 1b Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Phase 1b Unknown or Not Reported | 3 Participants | 6 Participants | 5 Participants | 14 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Phase 2 Hispanic or Latino | — | — | — | 1 Participants | 0 Participants | 1 Participants | — | — |
| Ethnicity (NIH/OMB) Phase 2 Not Hispanic or Latino | — | — | — | 35 Participants | 19 Participants | 16 Participants | — | — |
| Ethnicity (NIH/OMB) Phase 2 Unknown or Not Reported | — | — | — | 0 Participants | 0 Participants | 0 Participants | — | — |
| Ethnicity (NIH/OMB) Phase 2 Extension Hispanic or Latino | — | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Phase 2 Extension Not Hispanic or Latino | — | — | — | 14 Participants | — | — | 7 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Phase 2 Extension Unknown or Not Reported | — | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase 1b American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Phase 1b Asian | 3 Participants | 4 Participants | 2 Participants | 9 Participants | — | — | — | — |
| Race (NIH/OMB) Phase 1b Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Phase 1b More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Phase 1b Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Phase 1b Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race (NIH/OMB) Phase 1b White | 0 Participants | 2 Participants | 3 Participants | 5 Participants | — | — | — | — |
| Race (NIH/OMB) Phase 2 American Indian or Alaska Native | — | — | — | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Phase 2 Asian | — | — | — | 3 Participants | 3 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Phase 2 Black or African American | — | — | — | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Phase 2 More than one race | — | — | — | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Phase 2 Native Hawaiian or Other Pacific Islander | — | — | — | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Phase 2 Unknown or Not Reported | — | — | — | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Phase 2 White | — | — | — | 33 Participants | 16 Participants | 17 Participants | — | — |
| Race (NIH/OMB) Phase 2 Extension American Indian or Alaska Native | — | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase 2 Extension Asian | — | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase 2 Extension Black or African American | — | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase 2 Extension More than one race | — | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase 2 Extension Native Hawaiian or Other Pacific Islander | — | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase 2 Extension Unknown or Not Reported | — | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase 2 Extension White | — | — | — | 14 Participants | — | — | 7 Participants | 7 Participants |
| Sex: Female, Male Phase 1b Female | 2 Participants | 2 Participants | 1 Participants | 5 Participants | — | — | — | — |
| Sex: Female, Male Phase 1b Male | 1 Participants | 4 Participants | 4 Participants | 9 Participants | — | — | — | — |
| Sex: Female, Male Phase 2 Female | — | — | — | 13 Participants | 9 Participants | 4 Participants | — | — |
| Sex: Female, Male Phase 2 Male | — | — | — | 23 Participants | 10 Participants | 13 Participants | — | — |
| Sex: Female, Male Phase 2 Extension Female | — | — | — | 3 Participants | — | — | 1 Participants | 2 Participants |
| Sex: Female, Male Phase 2 Extension Male | — | — | — | 11 Participants | — | — | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 2 / 6 | 1 / 5 | 17 / 19 | 17 / 17 | 5 / 7 | 6 / 7 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 5 / 5 | 18 / 19 | 15 / 17 | 7 / 7 | 5 / 7 |
| serious Total, serious adverse events | 2 / 3 | 4 / 6 | 3 / 5 | 2 / 19 | 5 / 17 | 0 / 7 | 2 / 7 |
Outcome results
Primary
Phase 1b: Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.
Time frame: Up to approximately 7 months
Population: The Safety population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 1b: Number of Participants With Adverse Events (AEs) | 3 Participants |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 1b: Number of Participants With Adverse Events (AEs) | 6 Participants |
| Phase 1b: 50 μg IMU-131 Plus Chemotherapy | Phase 1b: Number of Participants With Adverse Events (AEs) | 5 Participants |
Primary
Phase 2 Extension: Number of Participants With AEs
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.
Time frame: From date of first dose to date of last dose plus 30 days (Up to 24 months)
Population: The Safety population included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2 Extension: Number of Participants With AEs | 7 Participants |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2 Extension: Number of Participants With AEs | 5 Participants |
Primary
Phase 2: Overall Survival (OS)
OS was measured from date of randomization to date of death due to any cause.
Time frame: Up to approximately 30 months
Population: The Intent-to-Treat population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2: Overall Survival (OS) | 13.90 months |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2: Overall Survival (OS) | 8.31 months |
p-value: 0.07880% CI: [0.38, 0.957]Log Rank
Secondary
Phase 2 and Phase 2 Extension: Disease Control Rate (DCR)
DCR was defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), or stable disease according to RECIST 1.1 after randomization/enrollment date.
Time frame: Up to approximately 30 months
Population: The Full Analysis Set (FAS) included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Disease Control Rate (DCR) | 77.8 percentage of participants |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Disease Control Rate (DCR) | 71.4 percentage of participants |
| Phase 1b: 50 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Disease Control Rate (DCR) | 71.4 percentage of participants |
| Phase 2 Extension: IMU-131 200 μg | Phase 2 and Phase 2 Extension: Disease Control Rate (DCR) | 85.7 percentage of participants |
Secondary
Phase 2 and Phase 2 Extension: Duration of Response (DOR)
DOR was defined as the time from the earliest date when a tumor response of CR or PR was observed until the date of first occurrence of disease progression which assessed by the blinded central reviewer or death (due to any reason).
Time frame: Up to approximately 30 months
Population: All randomized participants with a BOR of CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Duration of Response (DOR) | 7.10 months |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Duration of Response (DOR) | 4.40 months |
| Phase 1b: 50 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Duration of Response (DOR) | 3.65 months |
| Phase 2 Extension: IMU-131 200 μg | Phase 2 and Phase 2 Extension: Duration of Response (DOR) | 5.59 months |
Secondary
Phase 2 and Phase 2 Extension: Objective Response Rate (ORR)
ORR was defined as the proportion of participants with a BOR of CR or PR according RECIST 1.1 after randomization/enrollment date.
Time frame: Up to approximately 30 months
Population: The FAS included all randomized participants who received any amount of study treatment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Objective Response Rate (ORR) | 38.9 percentage of participants |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Objective Response Rate (ORR) | 50.0 percentage of participants |
| Phase 1b: 50 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Objective Response Rate (ORR) | 42.9 percentage of participants |
| Phase 2 Extension: IMU-131 200 μg | Phase 2 and Phase 2 Extension: Objective Response Rate (ORR) | 71.4 percentage of participants |
Secondary
Phase 2 and Phase 2 Extension: Percentage Change From Baseline in Tumor Size
Change in tumor size (CTS) was measured as the sum of diameters based on blinded central review according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1).
Time frame: Baseline up to approximately 30 months
Population: The ITT Population included all randomized participants. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Percentage Change From Baseline in Tumor Size | -22.4 percentage change from baseline |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Percentage Change From Baseline in Tumor Size | -34.4 percentage change from baseline |
| Phase 1b: 50 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Percentage Change From Baseline in Tumor Size | -43.1 percentage change from baseline |
| Phase 2 Extension: IMU-131 200 μg | Phase 2 and Phase 2 Extension: Percentage Change From Baseline in Tumor Size | -36.8 percentage change from baseline |
Secondary
Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS)
PFS was measured from randomization to date of earliest progressive disease (PD) based on blinded central review according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or to date of death from any cause.
Time frame: Up to approximately 30 months
Population: The ITT Population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS) | 6.93 months |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS) | 6.01 months |
| Phase 1b: 50 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS) | 5.03 months |
| Phase 2 Extension: IMU-131 200 μg | Phase 2 and Phase 2 Extension: Progression-Free Survival (PFS) | 8.34 months |
Secondary
Phase 2 and Phase 2 Extension: Time to Progression (TTP)
TTP was measured from randomization to date of earliest PD based on blinded central review according to RECIST 1.1 criteria.
Time frame: Up to approximately 30 months
Population: The ITT Population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Time to Progression (TTP) | 6.93 months |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Time to Progression (TTP) | 8.44 months |
| Phase 1b: 50 μg IMU-131 Plus Chemotherapy | Phase 2 and Phase 2 Extension: Time to Progression (TTP) | 5 months |
| Phase 2 Extension: IMU-131 200 μg | Phase 2 and Phase 2 Extension: Time to Progression (TTP) | 5.5 months |
Secondary
Phase 2 Extension: OS
OS was measured from date of randomization to date of death due to any cause.
Time frame: Up to 24 months
Population: The FAS included all randomized participants who received any amount of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: 10 μg IMU-131 Plus Chemotherapy | Phase 2 Extension: OS | 18.27 months |
| Phase 1b: 30 μg IMU-131 Plus Chemotherapy | Phase 2 Extension: OS | 9.36 months |