Pancreatic Adenocarcinoma
Conditions
Brief summary
A Phase Ib/II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in participants with metastatic Pancreatic Ductal Adenocarcinoma (PDAC). Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of patients who have received no prior systemic therapy for metastatic PDAC, and Cohort 2 will consist of patients who have received one line of prior systemic therapy for PDAC. In each cohort, eligible patients will be assigned to one of several treatment arms.
Interventions
DRUGNab-Paclitaxel
Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
DRUGGemcitabine
Gemcitabine will be administered as per the schedule specified in the respective arm.
DRUGOxaliplatin
Oxaliplatin will be administered as per the schedule specified in the respective arm.
DRUGLeucovorin
Leucovorin will be administered as per the schedule specified in the respective arm.
DRUGFluorouracil
Fluorouracil will be administered as per the schedule specified in the respective arm.
DRUGAtezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
DRUGCobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm.
DRUGPEGPH20
PEGPH20 will be administered as per the schedule specified in the respective arm.
DRUGBL-8040
BL-8040 will be administered as per the schedule specified in the respective arm.
DRUGSelicrelumab
Selicrelumab will be administered as per the schedule specified in the respective arm.
DRUGBevacizumab
Bevacizumab will be administered as per the schedule specified in the respective arm.
DRUGRO6874281
RO6874281 will be administered as per the schedule specified in the respective arm
DRUGAB928
AB928 will be administered as per the schedule specified in the respective arm.
DRUGTiragolumab
Tiragolumab will be administered as per the schedule specified in the respective arm.
DRUGTocilizumab
Tocilizumab will be administered as per the schedule specified in the respective arm.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma * For patients in Cohort 1: no prior systemic treatment for PDAC * For patients in Cohort 2: disease progression during administration of either 5-FU- or gemcitabine-based first-line chemotherapy * Life expectancy greater than or equal to 3 months * Availability of a representative tumor specimen that is suitable for determination of programmed death-ligand 1 (PD-L1) and/or additional biomarker status via central testing * Measurable disease (at least one target lesion) according to RECIST v1.1 * Adequate hematologic and end-organ function test results * Tumor accessible for biopsy * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as outlined for each specific treatment arm * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
Exclusion criteria
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage procedure (i.e., more than one time per month) * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * History of leptomeningeal disease * Active or history of autoimmune disease or immune deficiency * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * Positive human immunodeficiency (HIV) test at screening or at any time prior to screening * Active hepatitis B or C virus infection or active tuberculosis * Severe infection within 4 weeks prior to initiation of study treatment * Prior allogeneic stem cell or solid organ transplantation * History of malignancy other than pancreatic carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Up to 33.3 months | OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart during Stage 1 as determined by the investigator using RECIST v.1.1. Objective response rate (ORR) was defined as the percentage of participants with OR. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. 95% confidence intervals (CI) for rates were constructed using Clopper-Pearson method. Percentages have been rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | Up to 33.3 months | PFS was defined as the time from study treatment initiation to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (K-M) method was used to estimate PFS. |
| Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | Up to 33.3 months | OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS. |
| Number of Participants With Adverse Events (AEs) | Up to 33.3 months | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. |
| Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | Up to 33.3 months | DOR was defined as time from first occurrence of a documented OR until the time of documented PD or death from any cause, whichever occurs first as determined by investigator assessment using RECIST v1.1. DOR was calculated for participants who had a best confirmed OR of CR/PR. CR=the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR=at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. K-M method was used to estimate DOR. |
| Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | Up to 33.3 months | DC was defined as stable disease (SD) for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1 Disease control rate (DCR) was defined as the percentage of participants with DC. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages have been rounded off. |
| Stage 1: OS Rate at Month 6 | Month 6 | OS was defined as the time from randomization to death from any cause. OS rate at 6 months was defined as the percentage of participants who did not experience death from any cause at 6 months from randomization. K-M method was used to estimate OS. Percentages have been rounded off. |
Countries
Germany, Japan, South Korea, Spain, United States
Participant flow
Recruitment details
A total of 341 participants with metastatic pancreatic ductal adenocarcinoma (PDAC) took part in the study from 05 Jul 2017 to 27 Feb 2025. The study included participants in 2 cohorts: Cohort 1: received no prior systemic therapy for metastatic PDAC & Cohort 2: received 1 prior line of systemic therapy for PDAC. Multiple combination therapies were compared against common control(s) in Cohorts 1 and 2.
Pre-assignment details
Eligible participants from both cohorts were assigned to one of several treatment arms in Stage 1. Cohort 2 participants with disease progression (PD), loss of clinical benefit, or unacceptable toxicity in Stage 1 were eligible for a different treatment combination in Stage 2. The study is considered Completed because all the pre-planned study activities and analyses have been performed.
Participants by arm
| Arm | Count |
|---|---|
| Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) Participants received nab-paclitaxel, 125 mg/m\^2, IV infusion and gemcitabine, 1000 mg/m\^2, IV infusion on Days 1, 8, and 15 of each cycle until unacceptable toxicity or PD (1 cycle = 28 days). | 35 |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab Participants received atezolizumab, 840 mg, IV infusion on Days 1 and 15 of each cycle along with nab-paclitaxel, 125 mg/m\^2 and gemcitabine, 1000 mg/m\^2, also administered as IV infusion on Days 1, 8, and 15 of each cycle. Participants also received selicrelumab, 16 mg, SC injection on Day 1 of Cycles 1-4 and every third cycle thereafter (i.e. Cycles 7, 10, 13 etc.) of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 28 days). | 9 |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab Participants received atezolizumab, 840 mg, and bevacizumab, 10 mg/kg, IV infusion on Days 1 and 15 of each cycle along with nab-paclitaxel 125 mg/m\^2, and gemcitabine, 1000 mg/m\^2 also administered as IV infusion on Days 1, 8, and 15 of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 28 days). | 25 |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 Participants received AB928, 150 mg, orally, QD on Days 1 to 28 of each cycle; atezolizumab 840 mg, IV infusion on Days 1 and 15 of each cycle and nab-paclitaxel, 125 mg/m\^2, and gemcitabine, 1000 mg/m\^2, also administered as IV infusion, on Days 1, 8, and 15 of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 28 days). | 16 |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab Participants received atezolizumab, 840 mg and tiragolumab, 420 mg, IV infusion on Days 1 and 15 of each cycle along with nab-paclitaxel, 125 mg/m\^2 and gemcitabine, 1000 mg/m\^2, also administered as IV infusion on Days 1, 8, and 15 of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 28 days). | 42 |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab Participants received atezolizumab, 1680 mg and tocilizumab, 8 mg/kg, IV infusion on Days 1 of each cycle along with nab-paclitaxel, 125 mg/m\^2 and gemcitabine, 1000 mg/m\^2, also administered as IV infusion on Days 1, 8, and 15 of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 28 days). | 31 |
| Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) Participants who progressed on a prior gemcitabine-based regimen received mFOLFOX6 which is oxaliplatin, 85 mg/m\^2 and leucovorin, 400 mg/m\^2 as IV infusion, and 5-fluorouracil, 400 mg/m\^2, IV push on Days 1 and 15 of each cycle along with 5-fluorouracil, 2400 mg/m\^2, IV continuous infusion on Days 1, 2, 15 and 16 of each cycle until unacceptable toxicity or PD (1 cycle=28 days). | 25 |
| Stage 1 Cohort 2: Control (Nab-Paclitaxel and Gemcitabine) Participants who progressed on a prior fluoropyrimidine-based regimen received nab-paclitaxel, 125 mg/m\^2 and gemcitabine, 1000 mg/m\^2, also administered as IV infusion on Days 1, 8, and 15 of each cycle until unacceptable toxicity or PD (1 cycle=28 days). | 25 |
| Stage 1 Cohort 2: Atezolizumab + BL-8040 Participants received BL-8040, 1.25 mg/kg, SC injection on Days 1-5 of the first week, as priming treatment, and thereafter three times a week (Days 1, 3, 5, 8, 10, 12, 15, 17, and 19) along with atezolizumab, 1200 mg, IV infusion on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 21 days). | 16 |
| Stage 1 Cohort 2: Atezolizumab + Cobimetinib Participants received atezolizumab, 840 mg, IV infusion on Days 1 and 15 of each cycle and cobimetinib 60 mg, orally, QD on Days 1-21 of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 28 days). | 15 |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 Participants received atezolizumab, 1200 mg, IV infusion on Day 1 of each cycle and PEGPH20, 3 µg/kg, IV infusion on Days 1, 8 and 15 of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 21 days). | 71 |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q3W Participants received atezolizumab, 1200 mg, IV infusion and RO6874281, 10 mg, IV infusion on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit (1 cycle = 21 days). | 16 |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W Participants received atezolizumab, 840 mg, IV infusion on Days 1 and 15 of each cycle and RO6874281, 10 mg, IV infusion on Day 1 and 15 mg on Days 8, 15, and 22 of Cycle 1 and thereafter 15 mg on Days 1 and 15 of subsequent cycles until unacceptable toxicity or loss of clinical benefit (1 cycle = 28 days). | 15 |
| Total | 341 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1 | Arm Terminated by Sponsor | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage 1 | Death | 22 | 8 | 23 | 14 | 34 | 28 | 19 | 21 | 14 | 10 | 59 | 14 | 14 | 0 | 0 | 0 |
| Stage 1 | Lost to Follow-up | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage 1 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Stage 1 | Progressive Disease | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage 1 | Reason not Specified | 1 | 0 | 0 | 1 | 0 | 1 | 2 | 2 | 0 | 1 | 3 | 0 | 1 | 0 | 0 | 0 |
| Stage 1 | Study Terminated By Sponsor | 3 | 0 | 0 | 0 | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage 1 | Withdrawal by Subject | 6 | 0 | 1 | 0 | 2 | 0 | 3 | 2 | 2 | 4 | 9 | 1 | 0 | 0 | 0 | 0 |
| Stage 2 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 14 | 4 | 1 |
| Stage 2 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Stage 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W | Total | Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) | Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab | Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab | Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 | Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab | Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab | Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) | Stage 1 Cohort 2: Control (Nab-Paclitaxel and Gemcitabine) | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + RO6874281 Q3W |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-64 years | 8 Participants | 193 Participants | 15 Participants | 6 Participants | 13 Participants | 11 Participants | 26 Participants | 11 Participants | 9 Participants | 20 Participants | 8 Participants | 9 Participants | 49 Participants | 8 Participants |
| Age, Customized 65-84 years | 7 Participants | 148 Participants | 20 Participants | 3 Participants | 12 Participants | 5 Participants | 16 Participants | 20 Participants | 16 Participants | 5 Participants | 8 Participants | 6 Participants | 22 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 12 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 325 Participants | 33 Participants | 9 Participants | 23 Participants | 16 Participants | 36 Participants | 30 Participants | 25 Participants | 24 Participants | 16 Participants | 15 Participants | 68 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 105 Participants | 12 Participants | 1 Participants | 5 Participants | 8 Participants | 8 Participants | 12 Participants | 11 Participants | 6 Participants | 8 Participants | 4 Participants | 21 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 9 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 20 Participants | 5 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 203 Participants | 18 Participants | 4 Participants | 16 Participants | 7 Participants | 30 Participants | 15 Participants | 14 Participants | 19 Participants | 7 Participants | 9 Participants | 43 Participants | 10 Participants |
| Sex: Female, Male Female | 7 Participants | 134 Participants | 13 Participants | 4 Participants | 7 Participants | 8 Participants | 12 Participants | 11 Participants | 14 Participants | 11 Participants | 5 Participants | 5 Participants | 28 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 207 Participants | 22 Participants | 5 Participants | 18 Participants | 8 Participants | 30 Participants | 20 Participants | 11 Participants | 14 Participants | 11 Participants | 10 Participants | 43 Participants | 7 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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 23 / 32 | 8 / 9 | 23 / 25 | 14 / 15 | 34 / 41 | 28 / 30 | 19 / 23 | 21 / 23 | 14 / 15 | 11 / 14 | 60 / 66 | 14 / 15 | 14 / 14 | 14 / 14 | 5 / 6 | 1 / 1 |
| other Total, other adverse events | 32 / 32 | 9 / 9 | 23 / 25 | 15 / 15 | 40 / 41 | 30 / 30 | 21 / 23 | 23 / 23 | 15 / 15 | 13 / 14 | 65 / 66 | 15 / 15 | 14 / 14 | 13 / 14 | 6 / 6 | 0 / 1 |
| serious Total, serious adverse events | 13 / 32 | 8 / 9 | 17 / 25 | 4 / 15 | 19 / 41 | 12 / 30 | 10 / 23 | 12 / 23 | 4 / 15 | 8 / 14 | 30 / 66 | 7 / 15 | 2 / 14 | 7 / 14 | 2 / 6 | 0 / 1 |
Outcome results
Primary
Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart during Stage 1 as determined by the investigator using RECIST v.1.1. Objective response rate (ORR) was defined as the percentage of participants with OR. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. 95% confidence intervals (CI) for rates were constructed using Clopper-Pearson method. Percentages have been rounded off.
Time frame: Up to 33.3 months
Population: Efficacy population included participants in the safety population who received at least one dose of study drug and who had at least one baseline and one on-study tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 37.5 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 55.6 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 48.0 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 26.7 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 31.7 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 30.0 percentage of participants |
| Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 8.7 percentage of participants |
| Stage 1 Cohort 2: Control (Nab-Paclitaxel and Gemcitabine) | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + Cobimetinib | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 6.1 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q3W | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W | Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 7.1 percentage of participants |
95% CI: [-25.6, 61.71]
95% CI: [-18.85, 39.85]
95% CI: [-43.7, 22.03]
95% CI: [-30.58, 18.99]
95% CI: [-34.19, 19.19]
95% CI: [-25.96, 8.57]
95% CI: [-25.96, 8.57]
95% CI: [-18.44, 13.17]
95% CI: [-25.72, 8.33]
95% CI: [-25.04, 21.93]
Secondary
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
Time frame: Up to 33.3 months
Population: Safety population included all participants who received any amount of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) | Number of Participants With Adverse Events (AEs) | 32 Participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab | Number of Participants With Adverse Events (AEs) | 9 Participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab | Number of Participants With Adverse Events (AEs) | 24 Participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 | Number of Participants With Adverse Events (AEs) | 15 Participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab | Number of Participants With Adverse Events (AEs) | 41 Participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab | Number of Participants With Adverse Events (AEs) | 30 Participants |
| Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) | Number of Participants With Adverse Events (AEs) | 22 Participants |
| Stage 1 Cohort 2: Control (Nab-Paclitaxel and Gemcitabine) | Number of Participants With Adverse Events (AEs) | 23 Participants |
| Stage 1 Cohort 2: Atezolizumab + BL-8040 | Number of Participants With Adverse Events (AEs) | 15 Participants |
| Stage 1 Cohort 2: Atezolizumab + Cobimetinib | Number of Participants With Adverse Events (AEs) | 14 Participants |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Number of Participants With Adverse Events (AEs) | 65 Participants |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q3W | Number of Participants With Adverse Events (AEs) | 15 Participants |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W | Number of Participants With Adverse Events (AEs) | 14 Participants |
| Stage 2 Cohort 2: Atezolizumab + Cobimetinib | Number of Participants With Adverse Events (AEs) | 14 Participants |
| Stage 2 Cohort 2: Atezolizumab + RO6874281 Q3W | Number of Participants With Adverse Events (AEs) | 6 Participants |
| Stage 2 Cohort 2: Atezolizumab + RO6874281 Q2W | Number of Participants With Adverse Events (AEs) | 0 Participants |
Secondary
Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1
DOR was defined as time from first occurrence of a documented OR until the time of documented PD or death from any cause, whichever occurs first as determined by investigator assessment using RECIST v1.1. DOR was calculated for participants who had a best confirmed OR of CR/PR. CR=the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR=at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. K-M method was used to estimate DOR.
Time frame: Up to 33.3 months
Population: Efficacy population included participants in the safety population who received at least one dose of study drug and who had at least one baseline and one on-study tumor assessment. Overall number analyzed included participants with OR i.e responders.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 5.40 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 3.35 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 8.18 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 4.85 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 4.47 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 5.65 months |
| Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 3.37 months |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 8.15 months |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W | Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | 6.14 months |
95% CI: [0.24, 3.51]
95% CI: [0.23, 1.6]
95% CI: [0.44, 5.47]
95% CI: [0.35, 2.44]
95% CI: [0.24, 1.93]
Secondary
Stage 1: OS Rate at Month 6
OS was defined as the time from randomization to death from any cause. OS rate at 6 months was defined as the percentage of participants who did not experience death from any cause at 6 months from randomization. K-M method was used to estimate OS. Percentages have been rounded off.
Time frame: Month 6
Population: Efficacy population included participants in the safety population who received at least one dose of study drug and who had at least one baseline and one on-study tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) | Stage 1: OS Rate at Month 6 | 87.07 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab | Stage 1: OS Rate at Month 6 | 55.56 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab | Stage 1: OS Rate at Month 6 | 83.48 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 | Stage 1: OS Rate at Month 6 | 80.00 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab | Stage 1: OS Rate at Month 6 | 72.55 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab | Stage 1: OS Rate at Month 6 | 86.67 percentage of participants |
| Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) | Stage 1: OS Rate at Month 6 | 78.76 percentage of participants |
| Stage 1 Cohort 2: Control (Nab-Paclitaxel and Gemcitabine) | Stage 1: OS Rate at Month 6 | 53.45 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1: OS Rate at Month 6 | 27.78 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + Cobimetinib | Stage 1: OS Rate at Month 6 | 41.96 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1: OS Rate at Month 6 | 51.97 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q3W | Stage 1: OS Rate at Month 6 | 43.33 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W | Stage 1: OS Rate at Month 6 | 50.00 percentage of participants |
95% CI: [-66.07, 3.04]
95% CI: [-22.55, 15.37]
95% CI: [-30.52, 16.38]
95% CI: [-32.72, 3.68]
95% CI: [-17.38, 16.57]
95% CI: [-83.51, -18.46]
95% CI: [-70.43, -3.18]
95% CI: [-49.39, -4.2]
95% CI: [-67.44, -3.42]
95% CI: [-60.94, 3.42]
Secondary
Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1
OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS.
Time frame: Up to 33.3 months
Population: Efficacy population included participants in the safety population who received at least one dose of study drug and who had at least one baseline and one on-study tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 14.55 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 9.03 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 13.34 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 16.49 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 13.34 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 11.20 months |
| Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 6.77 months |
| Stage 1 Cohort 2: Control (Nab-Paclitaxel and Gemcitabine) | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 8.31 months |
| Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 4.47 months |
| Stage 1 Cohort 2: Atezolizumab + Cobimetinib | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 4.24 months |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 7.06 months |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q3W | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 4.70 months |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W | Stage 1: Overall Survival (OS), as Determined by Investigator According to RECIST v1.1 | 7.33 months |
95% CI: [0.59, 3]
95% CI: [0.71, 2.29]
95% CI: [0.45, 1.74]
95% CI: [0.58, 1.68]
95% CI: [0.59, 1.84]
95% CI: [0.87, 4.77]
95% CI: [0.6, 2.94]
95% CI: [0.48, 1.6]
95% CI: [0.68, 3.36]
95% CI: [0.44, 2.02]
Secondary
Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1
DC was defined as stable disease (SD) for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1 Disease control rate (DCR) was defined as the percentage of participants with DC. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages have been rounded off.
Time frame: Up to 33.3 months
Population: Efficacy population included participants in the safety population who received at least one dose of study drug and who had at least one baseline and one on-study tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 81.3 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 55.6 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 64.0 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 66.7 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 61.0 percentage of participants |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 66.7 percentage of participants |
| Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 30.4 percentage of participants |
| Stage 1 Cohort 2: Control (Nab-Paclitaxel and Gemcitabine) | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 34.8 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 0 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + Cobimetinib | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 0 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 18.2 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q3W | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 0 percentage of participants |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W | Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 7.1 percentage of participants |
Secondary
Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1
PFS was defined as the time from study treatment initiation to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (K-M) method was used to estimate PFS.
Time frame: Up to 33.3 months
Population: Efficacy population included participants in the safety population who received at least one dose of study drug and who had at least one baseline and one on-study tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1 Cohort 1 : Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine) | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 6.11 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 4.04 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 7.18 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + AB928 | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 8.21 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tiragolumab | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 5.82 months |
| Stage 1 Cohort 1: Atezolizumab + Chemotherapy + Tocilizumab | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 5.39 months |
| Stage 1 Cohort 2: Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]) | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 2.76 months |
| Stage 1 Cohort 2: Control (Nab-Paclitaxel and Gemcitabine) | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 2.53 months |
| Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 1.64 months |
| Stage 1 Cohort 2: Atezolizumab + Cobimetinib | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 1.28 months |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 1.51 months |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q3W | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 1.38 months |
| Stage 1 Cohort 2: Atezolizumab + RO6874281 Q2W | Stage 1: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 | 1.46 months |
95% CI: [0.48, 2.64]
95% CI: [0.66, 2.08]
95% CI: [0.29, 1.23]
95% CI: [0.67, 1.89]
95% CI: [0.61, 1.87]
95% CI: [0.96, 4.75]
95% CI: [1.54, 8.57]
95% CI: [0.68, 1.92]
95% CI: [0.72, 3.05]
95% CI: [0.84, 3.06]