Immunotherapy Combinations for Esophageal Cancer

Not currently recruiting at 55 trial locations

Overseen By Reference Study ID Number: YO39609 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: NSAIDs, Anticoagulants

Disqualifiers: Autoimmune disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 21

Duration: Up to 3-6 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new combinations of immunotherapy and chemotherapy to treat gastric and esophageal cancers that cannot be surgically removed or have metastasized. It tests various drug combinations, including Atezolizumab (an immunotherapy drug), to determine their safety and effectiveness in shrinking tumors. Individuals with esophageal cancer who have not received prior treatment or those with gastric cancer whose condition has worsened after specific chemotherapies may be suitable candidates for this trial. As a Phase 1/Phase 2 trial, the research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that chronic therapy with certain anti-inflammatory or anti-platelet agents is not allowed, and treatment with anticoagulation agents like warfarin is excluded. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of atezolizumab and tiragolumab is generally well-tolerated by patients. Studies have found this combination to be safe and to show early signs of tumor-fighting activity. The body handled these drugs together without major differences. Some patients experienced side effects, but these were usually manageable.

For the combination of atezolizumab with cisplatin and 5-fluorouracil (5-FU), studies also report good tolerance. This combination has been tested in patients who have undergone previous treatments, and most side effects were manageable and similar to those expected from chemotherapy.

When combined with cisplatin and 5-FU, atezolizumab and tiragolumab are also considered tolerable. Some patients experienced serious side effects, but these were not common. This combination has shown promise in treating esophageal cancer.

Overall, these treatments are still under study, but earlier research has focused on safety and patient tolerance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for esophageal cancer because they combine innovative immunotherapies like atezolizumab and tiragolumab with traditional chemotherapy agents like cisplatin and 5-fluorouracil (5-FU). Unlike the standard chemotherapy treatments, which mainly target rapidly dividing cells, these immunotherapies work by enhancing the body's immune response against cancer cells. Atezolizumab is a checkpoint inhibitor that blocks the PD-L1 protein, helping the immune system recognize and attack cancer cells, while tiragolumab targets the TIGIT pathway, offering another layer of immune activation. This combination approach aims to improve treatment effectiveness and provide a more robust attack on the cancer compared to conventional chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for esophageal and gastric cancer?

Research has shown that combining the drugs atezolizumab and tiragolumab with chemotherapy can help esophageal cancer patients live longer. In this trial, one arm will receive this combination, which studies have shown extends patient survival to an average of 15.7 months, compared to 11.1 months for those who received a placebo. Adding tiragolumab to atezolizumab improved the cancer's response to treatment by 37%. Another arm in this trial will receive atezolizumab with the chemotherapy drugs cisplatin and 5-fluorouracil (5-FU), a combination that has proven very effective in treating other types of cancer, suggesting potential benefits for esophageal cancer as well. These findings offer hope for better outcomes with these immunotherapy combinations. ^{1 3 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adults with advanced gastric or gastroesophageal junction cancer, or esophageal cancer who have not had certain treatments. They must be in good physical condition (ECOG 0-1), expect to live at least 3 months, and agree to use contraception. Excluded are those with uncontrolled hypertension, recent severe infections, significant heart disease, autoimmune diseases, HIV/HBV/HCV infection, CNS metastases risk factors for bleeding disorders.

Inclusion Criteria

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm;

Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm

Exclusion Criteria

Positive EBV viral capsid antigen IgM test at screening

My condition is not gastric cancer.

Positive test for human immunodeficiency virus (HIV) at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immunotherapy-based treatment combinations, including atezolizumab with various agents, depending on the cohort and arm

Up to 3-6 years

Visits every 21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 to 120 days after last dose

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if they progress on initial treatment

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil (5-FU)
• Atezolizumab
• Cisplatin
• Leucovorin
• Linagliptin
• Oxaliplatin
• Paclitaxel
• Ramucirumab
• Tiragolumab

Trial Overview The trial is testing combinations of immunotherapy and chemotherapy in patients with advanced gastric or esophageal cancers. It includes drugs like Atezolizumab and Tiragolumab alongside standard chemotherapies such as Cisplatin and Paclitaxel. Patients will be randomly assigned to different treatment groups.

How Is the Trial Designed?

Group I: 2L-4: Atezo + Linagliptin (Gastric Cancer) Experimental Treatment 2 Interventions

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.

Group II: 2L-3: Atezo + BL-8040 (Gastric Cancer) Experimental Treatment 2 Interventions

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.

Group III: 2L-2: Atezo + PEGPH20 (Gastric Cancer) Experimental Treatment 2 Interventions

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.

Group IV: 2L-1: Atezo + Cobi (Gastric Cancer) Experimental Treatment 2 Interventions

Participants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019.

Group V: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer) Experimental Treatment 5 Interventions

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.

Group VI: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer) Experimental Treatment 5 Interventions

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.

Group VII: 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort) Experimental Treatment 2 Interventions

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.

Group VIII: 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort) Experimental Treatment 3 Interventions

Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy.

Group IX: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort) Experimental Treatment 4 Interventions

Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy.

Group X: 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer) Active Control 2 Interventions

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.

Group XI: 1L-Control: mFOLFOX6 (Gastric Cancer) Active Control 3 Interventions

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.

Group XII: 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort) Active Control 2 Interventions

Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

BioLineRx, Ltd.

Industry Sponsor

Trials

24

Recruited

2,200+

Halozyme Therapeutics

Industry Sponsor

Trials

47

Recruited

3,400+

Published Research Related to This Trial

In a phase II study involving 50 patients with advanced oesophageal cancer, the addition of cetuximab to the standard treatment of 5-FU/cisplatin/docetaxel (TPF) and chemoradiotherapy resulted in a clinical complete response (cCR) rate of 12% and an overall response rate of 54%.

The median overall survival for patients who underwent complete surgical resection was significantly longer at 42.1 months compared to 24.9 months for those who did not have surgery, indicating that achieving a complete resection is crucial for improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. Alsina, M., Rivera, F., Ramos, FJ., et al.[2019]

The combination of nivolumab (an anti-PD-1 antibody) with irinotecan and a fluoropyrimidine showed a disease control rate of 73.3% in 15 patients with advanced unresectable gastroesophageal cancers, indicating potential efficacy in this challenging patient population.

The treatment was generally feasible, with a median progression-free survival of 7 months and overall survival of 13.3 months, although 33% of patients experienced dose delays or adjustments primarily due to fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. Rogers, JE., Xiao, L., Trail, A., et al.[2023]

In a phase II trial involving 24 patients with resectable esophageal carcinoma, the combination of neoadjuvant therapy using paclitaxel, carboplatin, 5-fluorouracil, and conformal radiotherapy resulted in a 57% pathologic complete response rate, indicating significant effectiveness in shrinking tumors before surgery.

The treatment showed a median overall survival of 31 months and a disease-free survival rate of 57% at 3 years, although some patients experienced significant side effects, including esophagitis and hypotension, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiotherapy for esophageal cancer using weekly Paclitaxel and Carboplatin plus infusional 5-Fluorouracil. Gannett, DE., Wolf, RF., Takahashi, GW., et al.[2022]

In a study of 30 patients with resectable esophageal squamous cell carcinoma, a chemotherapy regimen combining 5-fluorouracil, cisplatin, and interferon-alpha showed promising results, with a median overall survival of 26.3 months.

The treatment led to a complete pathological response in 4 out of 23 patients who underwent esophagectomy, indicating significant effectiveness, although there was one toxic death due to esophageal perforation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of neoadjuvant cisplatin, 5-fluorouracil and interferon-alpha in operable squamous cell carcinoma of the esophagus. Bazarbashi, S., Abdelsalam, M., Amin, T., et al.[2013]

In a study of 28 patients with unresectable or recurrent esophageal squamous cell carcinoma (ESCC), the combination of S-1 and paclitaxel (S1/PTX) showed a response rate of 14.8%, with a median overall survival time of 306 days, indicating some clinical efficacy in this difficult-to-treat population.

While S1/PTX was generally well-tolerated, severe neutropenia occurred in 13 patients, highlighting the need for monitoring blood counts during treatment, although most non-hematological side effects were mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. Nakajima, Y., Kawada, K., Tokairin, Y., et al.[2019]

In a Phase II study involving 64 patients with locally advanced esophageal squamous cell carcinoma, the combination of the PD-L1 inhibitor socazolimab with nab-paclitaxel and cisplatin showed promising efficacy, achieving a major pathological response (MPR) rate of 69.0% compared to 62.1% in the control group, although this difference was not statistically significant.

The socazolimab combination therapy resulted in a significantly higher rate of complete tumor downstaging (ypT0) at 37.9% compared to 3.5% in the control group, indicating a potential benefit in tumor reduction without increasing surgical complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial : A randomized clinical trial of neoadjuvant therapy for ESCC. Li, Y., Zhou, A., Liu, S., et al.[2023]

Nimotuzumab (h-R3) showed a weak inhibitory effect on the proliferation of human esophageal squamous cell carcinoma (ESCC) EC1 cells, with a maximum inhibition rate of only 10.10% after 48 hours, indicating limited efficacy as a standalone treatment.

Combining h-R3 with chemotherapeutic agents like cisplatin or fluorouracil did not significantly enhance the inhibition of cell growth or increase apoptosis rates compared to the chemotherapeutic agents alone, suggesting that h-R3 may not provide additional benefits in treating ESCC in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nimotuzumab with cisplatin or fluorouracil on human esophageal squamous cell carcinoma EC1 cells. Ji, YH., Yang, XY., Wu, JQ., et al.[2019]

Nivolumab and pembrolizumab, both PD-1 inhibitors, have shown significant improvements in overall survival (OS) for patients with esophageal carcinoma, particularly in combination with chemotherapy or ipilimumab, based on multiple landmark trials.

In the second-line treatment setting, monotherapy with nivolumab, pembrolizumab, and other PD-1 inhibitors also demonstrated improved OS compared to traditional chemotherapy, highlighting the effectiveness of immunotherapy in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Squamous Cell Cancer of the Esophagus. Thuss-Patience, P., Stein, A.[2022]

Citations

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TENERGY: multicenter phase II study of Atezolizumab ... An improved therapeutic efficacy by combining immunotherapy with radiation has been reported in patients with locally advanced non-small cell ...

2. nature.com nature.com/articles/s43018-025-00918-1

a multicenter phase 2 trial (EPOC1802) Atezolizumab monotherapy after dCRT resulted in a promising cCR rate, although long-term survival data are required. Similar content being ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32312286/

TENERGY: multicenter phase II study of Atezolizumab ... However, complete response (CR) rates are low at 11-25%, resulting in 9-10 months of median overall survival (OS). An improved therapeutic ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-020-06716-5

TENERGY: multicenter phase II study of Atezolizumab ... However, complete response (CR) rates are low at 11–25%, resulting in 9–10 months of median overall survival (OS). An improved therapeutic ...

5. sciencedirect.com sciencedirect.com/science/article/am/pii/S1470204524000810

Atezolizumab plus Modified DCF (Docetaxel, Cisplatin, and ... Background: The modified DCF (docetaxel/cisplatin/5-fluorouracil [mDCF]) regimen has demonstrated high efficacy and good tolerability as first-line treatment ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03281369

NCT03281369 | A Study of Multiple Immunotherapy-Based ... A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity ...

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Present situation and prospect of immunotherapy for ... Neoadjuvant chemotherapy combined with immunotherapy has good effectiveness and safety, which has been verified in the first-line chemotherapy combined with ...