AB308 + Zimberelimab for Advanced Cancers

(ARC-12 Trial)

No longer recruiting at 50 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Arcus Biosciences, Inc.

Must not be taking: Anti-TIGIT, Immunotherapy

Disqualifiers: Autoimmune disease, Recent surgery, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination of AB308 and zimberelimab (also known as AB122) for individuals with advanced cancers. It aims to determine the safety and tolerability of the treatment and its effects on cancer cells in the body. The trial includes different groups based on cancer type, such as gastric, esophageal, cervical, or blood cancers, and examines dosing schedules. Individuals diagnosed with any of these advanced cancers who haven't undergone recent major surgery or certain past treatments might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have had chemotherapy, targeted therapy, immunotherapy, or investigational drugs within 28 days before the first dose of the study treatment.

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

Research is examining the safety of combining AB308 and zimberelimab for individuals with advanced cancers. This marks the first human trial for AB308, so safety information is still being gathered. However, zimberelimab has undergone previous studies in other treatments.

In those earlier studies, patients generally tolerated zimberelimab well, experiencing few side effects. Common side effects included tiredness, fever, and skin rash, but these were usually mild.

As this trial is in an early phase, the primary goal is to assess safety and determine the optimal dose. Researchers are closely monitoring patient reactions to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for advanced cancers, like chemotherapy and radiation, attack rapidly dividing cells but can also harm healthy cells, leading to significant side effects. AB308 and zimberelimab, on the other hand, are part of a new wave of cancer therapies that harness the body's immune system to target and destroy cancer cells more precisely. Zimberelimab is a checkpoint inhibitor that blocks a protein called PD-1, which cancer cells use to avoid detection by the immune system. AB308 is designed to enhance this effect, potentially increasing the immune system's ability to fight cancer. Researchers are excited about this combination because it might offer a more targeted approach with fewer side effects, providing a new hope for patients with various advanced cancers.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research has shown that using AB308 with zimberelimab might help treat advanced cancers. These treatments are monoclonal antibodies, designed to target specific parts of cancer cells. By doing so, they can help stop cancer from growing or spreading. Early studies suggest this combination can enhance the immune system's ability to fight cancer. In this trial, participants will receive AB308 with zimberelimab across various dose escalation and expansion cohorts, targeting different cancers such as melanoma and cervical cancer. Initial results suggest this combination might be effective, but more research is needed to fully understand its potential. ^{1 2 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Arcus Biosciences

Are You a Good Fit for This Trial?

This trial is for adults with advanced malignancies like certain lymphomas, lung, stomach, esophageal cancers and more. Participants must be able to consent, have an ECOG score of 0 or 1 indicating they are fully active or restricted in physically strenuous activity but ambulatory, and have proper organ/marrow function. They should not have had severe reactions to past immunotherapies or recent surgeries and must agree to use contraception.

Inclusion Criteria

My organs and bone marrow are working well.

Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

I can sign and follow the study's consent form and rules.

Exclusion Criteria

I have not needed treatment for an autoimmune disease in the last 3 years.

I stopped immunotherapy due to severe side effects.

I have not had major surgery or serious injury in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Escalating doses of AB308 in combination with zimberelimab are administered every 3, 4, or 6 weeks to determine safety and tolerability

12-18 weeks

Visits every 3, 4, or 6 weeks depending on cohort

Dose Expansion

AB308 in combination with zimberelimab is administered at selected doses to evaluate clinical activity in specific cancer types

12-24 weeks

Visits every 3 or 4 weeks depending on cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AB308
• Zimberelimab

Trial Overview The study tests AB308 combined with Zimberelimab (AB122) on patients with advanced cancers. It's a Phase 1/1b trial that gradually increases doses to assess safety, how the body processes the drugs (PK), their effects on the body (PD), and their effectiveness against tumors.

How Is the Trial Designed?

Group I: Dose Expansion Cohort 5 Experimental Treatment 2 Interventions

AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with hematological malignancies.

Group II: Dose Expansion Cohort 4 Experimental Treatment 2 Interventions

AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with cervical cancer.

Group III: Dose Expansion Cohort 3 Experimental Treatment 2 Interventions

AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with metastatic gastric, or gastroesophageal junction, or esophageal cancer.

Group IV: Dose Expansion Cohort 2 Experimental Treatment 2 Interventions

AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with melanoma.

Group V: Dose Expansion Cohort 1 Experimental Treatment 2 Interventions

AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with in participants with locally advanced or metastatic NSCLC.

Group VI: Dose Escalation Q6W Cohort Experimental Treatment 2 Interventions

Selected dose of AB308 in combination with zimberelimab will be given every 6 weeks in participants with advanced malignancies.

Group VII: Dose Escalation Q4W Cohorts Experimental Treatment 2 Interventions

Escalating doses of AB308 in combination with zimberelimab (480 mg) will be given every 4 weeks in participants with advanced malignancies.

Group VIII: Dose Escalation Q3W Cohorts Experimental Treatment 2 Interventions

Escalating doses of AB308 in combination with zimberelimab (360 mg) will be given every 3 weeks in participants with advanced malignancies.

Who Is Running the Clinical Trial?

Arcus Biosciences, Inc.

Lead Sponsor

Trials

44

Recruited

7,500+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

In a study involving 21 Japanese patients with advanced solid tumors, the maximum tolerated dose (MTD) of BI 836880 was not reached, indicating a favorable safety profile for this treatment.

BI 836880, both as a monotherapy and in combination with ezabenlimab, showed preliminary clinical activity, with some patients experiencing stable disease and confirmed partial responses, suggesting potential efficacy in treating advanced tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of the VEGF/Ang-2 inhibitor BI 836880 alone or combined with the anti-programmed cell death protein-1 antibody ezabenlimab in Japanese patients with advanced solid tumors. Yamamoto, N., Koyama, T., Shimizu, T., et al.[2023]

The combination of ramucirumab and durvalumab was found to have manageable safety, with grade ≥3 treatment-related adverse events occurring in 32.1% of NSCLC, 37.9% of gastric/GEJ, and 42.9% of HCC patients, indicating that while there are risks, they are within acceptable limits for further study.

The treatment showed preliminary efficacy with an objective response rate of 11% for NSCLC and HCC, and 21% for gastric/GEJ, with better outcomes observed in patients with high PD-L1 expression, suggesting that this combination may be particularly beneficial for certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab and durvalumab for previously treated, advanced non-small-cell lung cancer, gastric/gastro-oesophageal junction adenocarcinoma, or hepatocellular carcinoma: An open-label, phase Ia/b study (JVDJ). Bang, YJ., Golan, T., Dahan, L., et al.[2023]

Zimberelimab is an anti-PD-1 monoclonal antibody that has been approved in China for treating relapsed or refractory classical Hodgkin's lymphoma based on a successful phase II trial.

The drug is being developed for various cancers, including cervical cancer and non-small cell lung cancer, highlighting its potential broad application in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zimberelimab: First Approval. Markham, A.[2022]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04772989?utm_source=trialradar

A Study to Evaluate AB308 in Combination With AB122 ... Escalating doses of AB308 in combination with zimberelimab (360 mg) will be given every 3 weeks in participants with advanced malignancies. Intervention/ ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04772989

A Study to Evaluate AB308 in Combination With AB122 ... AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with cervical cancer. Intervention/Treatment ...

3. ctv.veeva.com ctv.veeva.com/study/a-study-to-evaluate-ab308-in-combination-with-ab122-in-participants-with-advanced-malignancies

A Study to Evaluate AB308 in Combination With AB122 in ... AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with cervical cancer.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-05683

A Study to Evaluate AB308 in Combination With AB122 ... This is a Phase 1/1b, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), ...

5. withpower.com withpower.com/trial/phase-1-multiple-myeloma-2-2021-93934

AB308 + Zimberelimab for Advanced Cancers (ARC-12 Trial) Research shows that combining monoclonal antibodies, like those in AB308 and Zimberelimab, can target multiple pathways in cancer cells, potentially leading to ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)03641-3/fulltext

1028TiP ARC-12: Phase I/Ib dose escalation and ... This is a first-in-human, open-label study of AB308 + zim in pts with advanced malignancies. For the dose-escalation, pts must have solid tumors.

7. investors.arcusbio.com investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2025/Anti-TIGIT-Domvanalimab-Plus-Anti-PD-1-Zimberelimab-and-Chemotherapy-Showed-26-7-Months-of-Median-Overall-Survival-as-First-Line-Treatment-of-Unresectable-or-Advanced-Gastroesophageal-Adenocarcinomas-in-the-Phase-2-EDGE-Gastric-Study/default.aspx

Anti-TIGIT Domvanalimab Plus Anti-PD-1 Zimberelimab and ... First overall survival (OS) results from Arm A1 of the Phase 2 EDGE-Gastric study will be presented on October 18 at the European Society ...