Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal CarcinomaPhase 1/2NCT03281369
A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)
A Phase 1/2 study testing 5-Fluorouracil (5-FU), Leucovorin and Oxaliplatin in people with Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma, run by Hoffmann-La Roche at 28 sites in 7 countries.
Trial summary
A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with locally advanced unresectable or metastatic G/GEJ cancer (hereafter referred to as gastric cancer)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma
- What is being tested?
- 5-Fluorouracil (5-FU), Leucovorin and Oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 219 participants
- Where
- 28 sitesin 7 countries
- Study dates
- 13 Oct 2017to 9 Oct 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Gastric Cancer Cohorts Inclusion Criteria:
- Age >/= 18 years;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
- Life expectancy >/= 3 months, as determined by the investigator;
- Histologically or cytologically confirmed locally advanced unresectable or metastatic adenocarcinoma of gastric or gastroesophageal junction; (for the 1L Gastric Cancer Cohort: no prior systemic therapy for the locally advanced or metastatic disease; for the 2L Gastric Cancer Cohort: disease progression during or following a first-line platinum-containing or fluoropyrimidine-containing chemotherapy regimen);
- Availability of a representative tumor specimen that is suitable for determination of PD-L1 and TIGIT levels by IHC and/or additional biomarker status by means of retrospective central testing;
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- Only for the 1L Gastric Cancer Cohort: human epidermal growth factor receptor 2 (HER2)-negative tumors;
- Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1);
- Adequate hematologic and end organ function based on laboratory results obtained within 14 days prior to initiation of study treatment;
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures 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.
- Esophageal Cancer Cohort Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of squamous cell carcinoma or adenocarcinoma of the esophagus in locally advanced or metastatic disease;
- No prior systemic treatment for esophageal cancer, with the following exception:
- For patients treated with chemotherapy in the locally advanced setting: occurrence of metastasis after 6 months from the last dose of chemotherapy;
- For patients with adenocarcinoma: absence of HER2 expression;
- Life expectancy >/=3 months as determined by the investigator;
- Measurable disease per RECIST v1.1;
- Adequate hematologic and end-organ function;
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs;
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm;
- ECOG Performance Status of 0, 1, or 2.
Who cannot join
- Urinary protein is > 1 + on dipstick and the required following 24-hour urine collection shows urinary protein > 2000 mg;
- Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to initiation of study treatment;
- History of gastrointestinal perforation and/or fistulae within 6 months prior to initiation of study treatment;
- Presence of a bowel obstruction, history or presence of inflammatory enteropathy, or extensive intestinal resection, Crohn disease, ulcerative colitis, or chronic diarrhea;
- Uncontrolled arterial hypertension >/= 150/ >/= 90 millimeter of mercury (mmHg) despite standard medical management;
- Chronic therapy with non-steroidal anti-inflammatory agents or other anti-platelet agents.
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- Gastric Cancer Exclusion Criteria:
- Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy;
- 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 (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan;
- Positive test for human immunodeficiency virus (HIV) at screening;
- Active hepatitis B virus (HBV) or hepatitis C (HCV) infection;
- Severe infection within 4 weeks prior to initiation of study treatment;
- Significant cardiovascular disease;
- Significant bleeding disorder;
- Prior allogeneic stem cell or solid organ transplantation;
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study;
- Treatment with anticoagulation with warfarin, low-molecular-weight heparin, or similar agents for therapeutic purposes;
- History of malignancy other than gastric or gastroesophageal junction carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death;
- Known allergy or hypersensitivity to any of the study drugs or their excipients.
- Esophageal Cancer Cohort Exclusion Criteria:
- High risk for developing esophageal fistula by clinical assessment or imaging;
- Symptomatic, untreated, or actively progressing central nervous system (CNS) Metastases;
- Positive EBV viral capsid antigen IgM test at screening;
- 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;
- Active tuberculosis;
- Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina;
- History of malignancy other than esophageal cancer within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death;
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab or within 90 days after the final dose of tiragolumab.
Trial locations and contacts
28 sites in 7 countries.
28 sites in 7 countries
South Korea7 sites
Seoul National University Bundang Hospital
Gyeonggi-do, 13620
Korea University Anam Hospital
Seoul, 02841
Seoul National University Hospital
Seoul, 110-744
Samsung Medical Center
Seoul, 135-710
Yonsei University College of Medicine (YUCM)-Yonsei Cancer Center
Seoul
University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)
Songpa-gu, 05505
The Catholic University of Korea St. Vincent's Hospital
Suwon, 442-723
United States6 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4000
Uni of Southern California
Los Angeles, California, 90033
Tennessee Oncology - Nashville
Nashville, Tennessee, 37203
Columbia University Medical Center
New York, New York, 10032
UCLA Jonsson Comprehensive Cancer Center
Santa Monica, California, 90404
Mayo Clinic Cancer Center
Scottsdale, Arizona, 85259
United Kingdom5 sites
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)-CECM
London, 0
The Royal Marsden
London, SW7 3RP
The Christie NHS Foundation Trust
Manchester, M20 4BX
The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - Sutton
Sutton, SM2 5PT
Australia3 sites
Blacktown Hospital
Blacktown, New South Wales, 2148
Monash Medical Centre-Moorabbin Campus
Clayton, Victoria, 3168
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Taiwan3 sites
National Cheng Kung University Hospital
Tainan, 70457
National Taiwan University Hospital
Taipei, 100
Taipei Veterans General Hospital
Taipei, 11217
Israel2 sites
Rambam Health Care Campus
Haifa, 3109601
Sourasky Medical Centre
Tel Aviv, 64239
Spain2 sites
Hospital Universitari Vall dHebron
Barcelona, 08035
Universidad de Navarra - Clinica Universitaria de Navarra (CUN)
Pamplona, Navarre, 31008
About this study
Official title: A Phase Ib/II, Open-Label, Multicenter, Randomized, Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)
A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with locally advanced unresectable or metastatic G/GEJ cancer (hereafter referred to as gastric cancer) and esophageal cancer. Two cohorts of patients with gastric cancer have been enrolled in parallel in this study: the second-line (2L) Gastric Cancer Cohort consists of patients with gastric cancer who have progressed after receiving a platinum-containing or fluoropyrimide-containing chemotherapy regimen in the first-line setting, and the first-line (1L) Gastric Cancer Cohort consists of patients with gastric cancer who have not received prior chemotherapy in this setting. In each cohort, eligible patients will be assigned to one of several treatment arms. Additionally, a cohort of patients with esophageal cancer who have not received prior systemic treatment for their disease will be enrolled in this study. Eligible patients will be randomized to chemotherapy or the combination of chemotherapy with checkpoint inhibitor immunotherapy.
- Conditions
- Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma
- Being tested
- 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin, Atezolizumab, Cobimetinib
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-Fluorouracil (5-FU)Drug
5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
LeucovorinDrug
Also called Folinic acid
Leucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
OxaliplatinDrug
Oxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
AtezolizumabDrug
Also called Tecentriq
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
CobimetinibDrug
Also called Cotellic
Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
RamucirumabBiological
Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.
PaclitaxelDrug
Paclitaxel: 80 mg/m^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.
PEGylated recombinant human hyaluronidase (PEGPH20)Biological
PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle.
BL-8040Drug
BL-8040: 1.25 mg/kg administered by subcutaneous (SC) injection on Days 1-5 during the 5-day priming period prior to Cycle 1; 1.25 mg/kg administered by SC injection three times a week (Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of every 21-day cycle).
LinagliptinDrug
Linagliptin: 5 mg orally once a day of every 21-day cycle.
AtezolizumabDrug
Also called Tecentriq
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
CobimetinibDrug
Also called Cotellic
Cobimetinib: 40 or 60 mg (depending on the recommended dose determined during the safety run-in phase) by mouth once a day on Days 1-21 of every 28-day cycle.
CisplatinDrug
Cisplatin: 80 mg/m^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses.
TiragolumabDrug
Also called RO7092284
Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.
5-Fluorouracil (5-FU)Drug
5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| 1L-Control: mFOLFOX6 (Gastric Cancer) | Active comparator | Participants in the 1L Gastric Cancer Control arm will receive modified FOLFOX6 (mFOLFOX6) treatment consisting of 5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria. No longer enrolling participants as of June 2018. Receives: Drug: 5-Fluorouracil (5-FU); Drug: Leucovorin; Drug: Oxaliplatin |
| 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer) | Experimental | Participants in the 1L-A Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib. No longer enrolling participants as of June 2018. Receives: Drug: 5-Fluorouracil (5-FU); Drug: Leucovorin; Drug: Oxaliplatin; Drug: Atezolizumab; Drug: Cobimetinib |
| 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer) | Experimental | Participants in the 1L-A2 Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab during cycles 1 and 2 followed by atezolizumab plus cobimetinib during cycles 3 and beyond. No longer enrolling participants as of June 2018. Receives: Drug: 5-Fluorouracil (5-FU); Drug: Leucovorin; Drug: Oxaliplatin; Drug: Atezolizumab; Drug: Cobimetinib |
| 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer) | Active comparator | Participants in the 2L Gastric Cancer Control arm received ramucirumab plus paclitaxel. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019. Receives: Biological: Ramucirumab; Drug: Paclitaxel |
| 2L-1: Atezo + Cobi (Gastric Cancer) | Experimental | Participants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019. Receives: Drug: Atezolizumab; Drug: Cobimetinib |
| 2L-2: Atezo + PEGPH20 (Gastric Cancer) | Experimental | Participants in the 2L-2 Gastric Cancer arm received atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019. Receives: Biological: PEGylated recombinant human hyaluronidase (PEGPH20); Drug: Atezolizumab |
| 2L-3: Atezo + BL-8040 (Gastric Cancer) | Experimental | Participants in the 2L-3 Gastric Cancer arm received atezolizumab in combination with BL-8040. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019. Receives: Drug: BL-8040; Drug: Atezolizumab |
| 2L-4: Atezo + Linagliptin (Gastric Cancer) | Experimental | Participants in the 2L-4 Gastric Cancer arm received atezolizumab in combination with linagliptin. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019. Receives: Drug: Linagliptin; Drug: Atezolizumab |
| 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort) | Experimental | Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy. Receives: Drug: Atezolizumab; Drug: Cisplatin; Drug: Tiragolumab; Drug: 5-Fluorouracil (5-FU) |
| 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort) | Experimental | Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy. Receives: Drug: Atezolizumab; Drug: Cisplatin; Drug: 5-Fluorouracil (5-FU) |
| 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort) | Active comparator | Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy. Receives: Drug: Cisplatin; Drug: 5-Fluorouracil (5-FU) |
| 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort) | Experimental | Participants in the 1L-3 Esophageal Cancer arm will receive atezolizumab + tiragolumab treatment. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy. Receives: Drug: Atezolizumab; Drug: Tiragolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to 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 and non-target lesions. Any pathological lymph nodes (whether target or non-target) must 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 all target lesions, taking as reference the baseline SOD, in the absence of CR. 95% confidence intervals (CI) for rates were constructed using Clopper-Pearson method. Percentages have been rounded off.
Measured: From randomization up to approximately 84.2 months
Secondary outcomes (12)
Stage 1: Progression Free Survival (PFS) After Randomization, as Determined by Investigator According to RECIST v1.1
PFS was defined as the time from randomization to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred 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 or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, PFS was censored at the day of the last tumor assessment. Kaplan-Meier (K-M) method was used to estimate PFS.
Measured: From randomization to the first occurrence of PD or death (up to approximately 84.2 months)
Stage 1: Overall Survival (OS) After Randomization
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. K-M methodology was used to estimate the median OS.
Measured: From randomization to death (up to approximately 84.2 months)
Stage 1: OS at Month 6 and Month 12
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The K-M approach was used to estimate the percentage of participants who were event-free for OS at Month 6 and Month 12. Percentages have been rounded off.
Measured: At Months 6 and 12
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 as determined by investigator assessment using RECIST v1.1 or death from any cause, whichever occurs first. CR was defined as the disappearance of all target \& non-target lesions or any pathological lymph nodes (whether target or non-target) having 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, in the absence of CR. 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 or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, DOR was censored at the day of the last tumor assessment. K-M method was used to estimate DOR.
Measured: Up to approximately 84.2 months
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 ≥16 weeks for GC cohort or ≥ 12 weeks for esophageal cancer cohort, or CR/PR, as determined by investigator per RECIST v1.1. Disease control rate (DCR) was defined as percentage of participants with DC. CR was defined as disappearance of all target \& non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in SOD of target lesions, taking as reference baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least 20% increase in SOD of target lesions, taking as reference smallest sum on study including baseline (nadir). Additionally, the sum must also demonstrate absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Percentages have been rounded off.
Measured: Up to approximately 84.2 months
Stages 1 and 2: Percentage of Participants With Adverse Events (AEs)
An AE was defined as 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.
Measured: Stage 1: Up to 84.2 months; Stage 2: Up to 42.6 months
Stage 1: Serum Concentration of Atezolizumab
1 cycle = 21 days for the all three reported arms: Stage 1 Cohort 2: Atezolizumab + PEGPH20, Stage 1: Atezolizumab + Cisplatin + 5-FU" cohorts and Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU" cohort.
The protocol pre-specified that PK assessments could be conducted only for treatment combinations selected by the sponsor for further development. As the sponsor decided not to continue further development of the mFOLFOX6 + atezolizumab + cobimetinib, atezolizumab + linagliptin, and atezolizumab + BL-8040 combinations, PK data were not reported for these cohorts.
Measured: Pre-dose, 30 minutes (min) post-dose (infusion=60 min) on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20, 24, & 28; Stage 1 treatment discontinuation (TD) (up to approximately 82.7 months)
Stage 1: Serum Concentration of Tiragolumab
Measured: Pre-dose, 30 min post-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20, 24, & 28 (1 Cycle=28 days); Stage 1 TD (up to approximately 46.7 months)
Stage 1: Plasma Concentration of PEGPH20
1 Cycle=21 days
Measured: Pre-dose: Day 1 of Cycles 1, 2, 3, 4 & Days 8, 15 of Cycle 1; 5 minutes & 1-3 hours post-dose: Day 1 Cycle 1; 5 min post-dose: Day 1 Cycle 2; Stage 1: TD (up to approx 3.3 months) & Day 120 post last dose of atezo (up to approx 6.8 months)
Stage 1: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Atezolizumab
Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample have been reported here.
The protocol pre-specified that ADA assessments could be conducted only for treatment combinations selected by the sponsor for further development. As the sponsor decided not to continue further development of the mFOLFOX6 + atezolizumab + cobimetinib, atezolizumab + linagliptin, and atezolizumab + BL-8040 combinations, ADA data were not reported for these cohorts.
Measured: Up to approximately 82.7 months
Stage 1: Number of Participants With Treatment-emergent ADAs to Tiragolumab
Participants who received tiragolumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following tiragolumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
Measured: Up to approximately 46.7 months
Stage 1: Number of Participants With Treatment-emergent ADAs to PEGPH20
Participants who received PEGPH20 were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following PEGPH20 exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
Measured: Up to approximately 3.3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2017
- Study start13 Oct 2017
- Primary completion9 Oct 2025
- Study completion9 Oct 2025
Why it stopped: The study was closed because the sponsor decided not to continue the development of certain treatment combinations.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal CarcinomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 219 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Halozyme Therapeutics, BioLineRx, Ltd.
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03281369
- Sponsor's protocol ID
- YO39609
- Other IDs
- 2016-004529-17, 2016
- Status last verified
- Jul 2026
- First submitted
- 11 Sep 2017
- Last updated
- 3 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
Publications
Sun JM, Chao Y, Kim SB, Rha SY, Evans TRJ, Strickland AH, Wainberg Z, Chau I, Pelles-Avraham S, Ajani J, Malhotra R, Liu Q, Li S, Cha E, Kalaitzidou M, Huang X, Allen S, Hsu CH. First-line tiragolumab plus atezolizumab and chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic oesophageal cancer (MORPHEUS-EC): a randomised, open-label, phase 1b/2 trial. Lancet Oncol. 2026 Jan;27(1):90-102. doi: 10.1016/S1470-2045(25)00402-4.
PubMed 41449151Ko AH, Kim KP, Siveke JT, Lopez CD, Lacy J, O'Reilly EM, Macarulla T, Manji GA, Lee J, Ajani J, Alsina Maqueda M, Rha SY, Lau J, Al-Sakaff N, Allen S, Lu D, Shemesh CS, Gan X, Cha E, Oh DY. Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform. Oncologist. 2023 Jun 2;28(6):553-e472. doi: 10.1093/oncolo/oyad022.
PubMed 36940261
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II, Open-Label, Multicenter, Randomized, Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)
- ClinicalTrials.gov ID
- NCT03281369
- Acronym / sponsor ID
- YO39609
- Conditions
- Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was closed because the sponsor decided not to continue the development of certain treatment combinations.
- Enrolment
- 219 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Collaborators
- Halozyme Therapeutics, BioLineRx, Ltd.
- Study start
- 13 Oct 2017 (actual)
- Primary completion
- 9 Oct 2025 (actual)
- Study completion
- 9 Oct 2025 (actual)
- First posted
- 13 Sep 2017 (actual)
- Results
- Posted 3 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with locally advanced unresectable or metastatic G/GEJ cancer (hereafter referred to as gastric cancer) and esophageal cancer. Two cohorts of patients with gastric cancer have been enrolled in parallel in this study: the second-line (2L) Gastric Cancer Cohort consists of patients with gastric cancer who have progressed after receiving a platinum-containing or fluoropyrimide-containing chemotherapy regimen in the first-line setting, and the first-line (1L) Gastric Cancer Cohort consists of patients with gastric cancer who have not received prior chemotherapy in this setting. In each cohort, eligible patients will be assigned to one of several treatment arms. Additionally, a cohort of patients with esophageal cancer who have not received prior systemic treatment for their disease will be enrolled in this study. Eligible patients will be randomized to chemotherapy or the combination of chemotherapy with checkpoint inhibitor immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| 1L-Control: mFOLFOX6 (Gastric Cancer) | Active comparator | Drug: 5-Fluorouracil (5-FU), Drug: Leucovorin, Drug: OxaliplatinParticipants in the 1L Gastric Cancer Control arm will receive modified FOLFOX6 (mFOLFOX6) treatment consisting of 5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria. No longer enrolling participants as of June 2018. |
| 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer) | Experimental | Drug: 5-Fluorouracil (5-FU), Drug: Leucovorin, Drug: Oxaliplatin, Drug: Atezolizumab, Drug: CobimetinibParticipants in the 1L-A Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib. No longer enrolling participants as of June 2018. |
| 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer) | Experimental | Drug: 5-Fluorouracil (5-FU), Drug: Leucovorin, Drug: Oxaliplatin, Drug: Atezolizumab, Drug: CobimetinibParticipants in the 1L-A2 Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab during cycles 1 and 2 followed by atezolizumab plus cobimetinib during cycles 3 and beyond. No longer enrolling participants as of June 2018. |
| 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer) | Active comparator | Biological: Ramucirumab, Drug: PaclitaxelParticipants in the 2L Gastric Cancer Control arm received ramucirumab plus paclitaxel. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019. |
| 2L-1: Atezo + Cobi (Gastric Cancer) | Experimental | Drug: Atezolizumab, Drug: CobimetinibParticipants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019. |
| 2L-2: Atezo + PEGPH20 (Gastric Cancer) | Experimental | Biological: PEGylated recombinant human hyaluronidase (PEGPH20), Drug: AtezolizumabParticipants in the 2L-2 Gastric Cancer arm received atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019. |
| 2L-3: Atezo + BL-8040 (Gastric Cancer) | Experimental | Drug: BL-8040, Drug: AtezolizumabParticipants in the 2L-3 Gastric Cancer arm received atezolizumab in combination with BL-8040. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019. |
| 2L-4: Atezo + Linagliptin (Gastric Cancer) | Experimental | Drug: Linagliptin, Drug: AtezolizumabParticipants in the 2L-4 Gastric Cancer arm received atezolizumab in combination with linagliptin. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019. |
| 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort) | Experimental | Drug: Atezolizumab, Drug: Cisplatin, Drug: Tiragolumab, Drug: 5-Fluorouracil (5-FU)Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy. |
| 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort) | Experimental | Drug: Atezolizumab, Drug: Cisplatin, Drug: 5-Fluorouracil (5-FU)Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy. |
| 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort) | Active comparator | Drug: Cisplatin, Drug: 5-Fluorouracil (5-FU)Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy. |
| 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort) | Experimental | Drug: Atezolizumab, Drug: TiragolumabParticipants in the 1L-3 Esophageal Cancer arm will receive atezolizumab + tiragolumab treatment. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Age >/= 18 years;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
- Life expectancy >/= 3 months, as determined by the investigator;
- Histologically or cytologically confirmed locally advanced unresectable or metastatic adenocarcinoma of gastric or gastroesophageal junction; (for the 1L Gastric Cancer Cohort: no prior systemic therapy for the locally advanced or metastatic disease; for the 2L Gastric Cancer Cohort: disease progression during or following a first-line platinum-containing or fluoropyrimidine-containing chemotherapy regimen);
- Availability of a representative tumor specimen that is suitable for determination of PD-L1 and TIGIT levels by IHC and/or additional biomarker status by means of retrospective central testing;
Key exclusion criteria (33 listed)
- Urinary protein is > 1 + on dipstick and the required following 24-hour urine collection shows urinary protein > 2000 mg;
- Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to initiation of study treatment;
- History of gastrointestinal perforation and/or fistulae within 6 months prior to initiation of study treatment;
- Presence of a bowel obstruction, history or presence of inflammatory enteropathy, or extensive intestinal resection, Crohn disease, ulcerative colitis, or chronic diarrhea;
- Uncontrolled arterial hypertension >/= 150/ >/= 90 millimeter of mercury (mmHg) despite standard medical management;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-Fluorouracil (5-FU)5-FU 2400 milligrams per square meter (mg/m^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle. | Drug | 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer), 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer), 1L-Control: mFOLFOX6 (Gastric Cancer) |
| LeucovorinAlso: Folinic acidLeucovorin: 100 mg/m^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle. | Drug | 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer), 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer), 1L-Control: mFOLFOX6 (Gastric Cancer) |
| OxaliplatinOxaliplatin: 100 mg/m^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle. | Drug | 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer), 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer), 1L-Control: mFOLFOX6 (Gastric Cancer) |
| AtezolizumabAlso: TecentriqAtezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle. | Drug | 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer), 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer), 2L-1: Atezo + Cobi (Gastric Cancer) |
| CobimetinibAlso: CotellicCobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle | Drug | 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer), 2L-1: Atezo + Cobi (Gastric Cancer) |
| RamucirumabRamucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle. | Biological | 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer) |
| PaclitaxelPaclitaxel: 80 mg/m^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle. | Drug | 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer) |
| PEGylated recombinant human hyaluronidase (PEGPH20)PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle. | Biological | 2L-2: Atezo + PEGPH20 (Gastric Cancer) |
| BL-8040BL-8040: 1.25 mg/kg administered by subcutaneous (SC) injection on Days 1-5 during the 5-day priming period prior to Cycle 1; 1.25 mg/kg administered by SC injection three times a week (Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of every 21-day cycle). | Drug | 2L-3: Atezo + BL-8040 (Gastric Cancer) |
| LinagliptinLinagliptin: 5 mg orally once a day of every 21-day cycle. | Drug | 2L-4: Atezo + Linagliptin (Gastric Cancer) |
| AtezolizumabAlso: TecentriqAtezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle | Drug | 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort), 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort), 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort), 2L-2: Atezo + PEGPH20 (Gastric Cancer), 2L-3: Atezo + BL-8040 (Gastric Cancer), 2L-4: Atezo + Linagliptin (Gastric Cancer) |
| CobimetinibAlso: CotellicCobimetinib: 40 or 60 mg (depending on the recommended dose determined during the safety run-in phase) by mouth once a day on Days 1-21 of every 28-day cycle. | Drug | 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer) |
| CisplatinCisplatin: 80 mg/m^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses. | Drug | 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort), 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort), 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort) |
| TiragolumabAlso: RO7092284Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle. | Drug | 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort), 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort) |
| 5-Fluorouracil (5-FU)5-FU 800 mg/m^2 administerd by IV infusion on Days 1-5 of each 21 day cycle. | Drug | 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort), 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort), 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort) |
Primary outcome
Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to RECIST v1.1
Time frame: From randomization up to approximately 84.2 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 and non-target lesions. Any pathological lymph nodes (whether target or non-target) must 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 all target lesions, taking as reference the baseline SOD, in the absence of CR. 95% confidence intervals (CI) for rates were constructed using Clopper-Pearson method. Percentages have been rounded off.
12 secondary outcomes
Stage 1: Progression Free Survival (PFS) After Randomization, as Determined by Investigator According to RECIST v1.1
Time frame: From randomization to the first occurrence of PD or death (up to approximately 84.2 months)
Stage 1: Overall Survival (OS) After Randomization
Time frame: From randomization to death (up to approximately 84.2 months)
Stage 1: OS at Month 6 and Month 12
Time frame: At Months 6 and 12
Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1
Time frame: Up to approximately 84.2 months
Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1
Time frame: Up to approximately 84.2 months
Stages 1 and 2: Percentage of Participants With Adverse Events (AEs)
Time frame: Stage 1: Up to 84.2 months; Stage 2: Up to 42.6 months
Stage 1: Serum Concentration of Atezolizumab
Time frame: Pre-dose, 30 minutes (min) post-dose (infusion=60 min) on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20, 24, & 28; Stage 1 treatment discontinuation (TD) (up to approximately 82.7 months)
Stage 1: Serum Concentration of Tiragolumab
Time frame: Pre-dose, 30 min post-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20, 24, & 28 (1 Cycle=28 days); Stage 1 TD (up to approximately 46.7 months)
Stage 1: Plasma Concentration of PEGPH20
Time frame: Pre-dose: Day 1 of Cycles 1, 2, 3, 4 & Days 8, 15 of Cycle 1; 5 minutes & 1-3 hours post-dose: Day 1 Cycle 1; 5 min post-dose: Day 1 Cycle 2; Stage 1: TD (up to approx 3.3 months) & Day 120 post last dose of atezo (up to approx 6.8 months)
Stage 1: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Atezolizumab
Time frame: Up to approximately 82.7 months
Stage 1: Number of Participants With Treatment-emergent ADAs to Tiragolumab
Time frame: Up to approximately 46.7 months
Stage 1: Number of Participants With Treatment-emergent ADAs to PEGPH20
Time frame: Up to approximately 3.3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41449151Sun JM, Chao Y, Kim SB, Rha SY, Evans TRJ, Strickland AH, Wainberg Z, Chau I, Pelles-Avraham S, Ajani J, Malhotra R, Liu Q, Li S, Cha E, Kalaitzidou M, Huang X, Allen S, Hsu CH. First-line tiragolumab plus atezolizumab and chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic oesophageal cancer (MORPHEUS-EC): a randomised, open-label, phase 1b/2 trial. Lancet Oncol. 2026 Jan;27(1):90-102. doi: 10.1016/S1470-2045(25)00402-4.
- Derived from this study: PubMed 36940261Ko AH, Kim KP, Siveke JT, Lopez CD, Lacy J, O'Reilly EM, Macarulla T, Manji GA, Lee J, Ajani J, Alsina Maqueda M, Rha SY, Lau J, Al-Sakaff N, Allen S, Lu D, Shemesh CS, Gan X, Cha E, Oh DY. Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform. Oncologist. 2023 Jun 2;28(6):553-e472. doi: 10.1093/oncolo/oyad022.
- Individual participant dataSharing planned: Yes. For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
28 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 5-Fluorouracil (5-FU), Leucovorin and Oxaliplatin in people with Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma, run by Hoffmann-La Roche at 28 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in South Korea, United States, United Kingdom, Australia, Taiwan and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to RECIST v1.1 (time frame: From randomization up to approximately 84.2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03281369, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.