AB308 + Zimberelimab for Advanced Cancers

(ARC-12 Trial)

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

94 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1/1b, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of AB308 in combination with zimberelimab (AB122) in participants with advanced malignancies.

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.

What data supports the effectiveness of the drug AB308 + Zimberelimab for advanced cancers?

Research shows that combining monoclonal antibodies, like those in AB308 and Zimberelimab, can target multiple pathways in cancer cells, potentially leading to better outcomes. Similar combinations have shown benefits in other cancers, such as improved survival rates in advanced melanoma with different antibody combinations. ^{1 2 3 4 5}

What makes the drug AB308 + Zimberelimab unique for advanced cancers?

The combination of AB308 and Zimberelimab is unique because Zimberelimab is an anti-PD-1 monoclonal antibody, which helps the immune system recognize and attack cancer cells, and it has been approved for certain types of cancer in China. This combination may offer a novel approach by potentially enhancing the immune response against advanced cancers. ^{6 7 8 9 10}

Research Team

Medical Director

Principal Investigator

Arcus Biosciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Durvalumab in NSCLC: latest evidence and clinical potential. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The use of combinations of monoclonal antibodies in clinical oncology. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Anlotinib combined with anti-PD-1 antibody, camrelizumab for advanced NSCLCs after multiple lines treatment: An open-label, dose escalation and expansion study. [2022]

5. England 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). [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Zimberelimab: First Approval. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Phase 1 study of AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adults with advanced solid tumors. [2020]

8. England pubmed.ncbi.nlm.nih.gov

First-in-human, dose-escalation, phase 1 study of anti-angiopoietin-2 LY3127804 as monotherapy and in combination with ramucirumab in patients with advanced solid tumours. [2023]

9. Germany 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. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study. [2021]