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Non-small Cell Lung CancerPhase 1NCT03629756

A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies

A Phase 1 study testing Etrumadenant and Zimberelimab in people with Non-small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck, run by Arcus Biosciences, Inc. at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity of etrumadenant (AB928) in combination with zimberelimab (AB122) (an anti-PD-1 antibody) in participants with advanced malignancies. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Etrumadenant and Zimberelimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
15 sitesin 2 countries
Study dates
24 Jul 2018to 3 Sep 2021
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Male or female participants ≥ 18 years
  • Must have at least 1 measurable lesion per RECIST v1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  • Must have received standard of care, including potentially curative available therapies or interventions.
  • Confirm that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor lesion must be obtained. Biopsy must not put participant at undue risk and the procedure must not be more invasive than a core biopsy.
  • Adequate organ and marrow function
Show all 12Show fewer
  • Dose escalation only:
  • Pathologically confirmed non-small cell lung cancer, squamous cell carcinoma of the head and neck, renal cell carcinoma, breast cancer, colorectal cancer, melanoma, bladder cancer, ovarian cancer, endometrial cancer, Merkel cell carcinoma, or gastroesophageal cancer that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists or standard therapy is not considered appropriate by the participant and treating physician (reason must be documented in medical records).
  • Dose expansion only:
  • Participants with advanced clear-cell RCC or mCRPC.9. Clear-cell RCC participants may have received up to 2 prior lines of therapy, one of which must have included an anti-PD-(L)1 based therapy and must not have progressed within 16 weeks during an anti-PD-(L)1 therapy.
  • mCRPC participants must have progressed during or following treatment with an androgen synthesis inhibitor, and have also had one prior line of a taxane-containing regimen or the physician and participant consider the taxane-containing regimen to be inappropriate.
  • mCRPC participants must be naive to any immunotherapy (including but not limited to anti-PD-(L)1 or anti-CTLA-4 antagonists, sipuleucel-T, etc.).

Who cannot join

  • Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product.
  • Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational product hazardous (eg, interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms) or obscure the interpretation of toxicity determination or AEs, or concurrent medical condition requiring the use of immunosuppressive medications or immunosuppressive doses of systemic or absorbable topical corticosteroids.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 90 days after the last dose of etrumadenant in combination with zimberelimab.
  • Any active or documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.
  • Prior malignancy active within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, breast, or prostate cancer.
  • Dose escalation: Prior treatment with an anti-PD-L1, anti-PD-1, anti-CTLA-4, or other immune checkpoint inhibitor or agonist as a monotherapy or in combination;
  • Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before investigational product administration.

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States12 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Rocky Mountain Cancer Centers (Midtown)

    Denver, Colorado, 80218

  • Texas Oncology, P.A. - Fort Worth Cancer Center

    Fort Worth, Texas, 76104

  • Prisma Health

    Greenville, South Carolina, 29605

  • Carolina BioOncology Institute

    Huntersville, North Carolina, 28078

  • University of California, Los Angeles

    Los Angeles, California, 90024

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • QUEST Research Institute

    Royal Oak, Michigan, 48073

  • Texas Oncology, P.A. - San Antonio Medical Center

    San Antonio, Texas, 78240

  • Scottsdale Healthcare Hospitals dba HonorHealth

    Scottsdale, Arizona, 85258

  • Medical Oncology Associates dba Summit Cancer Centers

    Spokane, Washington, 99208

  • Texas Oncology, P.A. - Tyler

    Tyler, Texas, 75702

Other trials in United States

Australia3 sites

  • Gallipoli Medical Research Foundation

    Greenslopes, Queensland, 4120

  • St. George Private Hospital

    Kogarah, New South Wales, 2217

  • Cabrini Health Limited

    Malvern, 3144

Other trials in Australia

About this study

Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies

This is a Phase 1, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity of etrumadenant (AB928) in combination with zimberelimab (AB122) (an anti-PD-1 antibody) in participants with advanced malignancies.

Read the detailed description

In the dose-escalation phase, escalating doses of etrumadenant in combination with zimberelimab will be assessed in participants with advanced malignancies. Eligible participants will receive oral administration of etrumadenant as well as IV infusion of zimberelimab. The recommended Phase 2 dose (RP2D) of etrumadenant will be determined upon completion of the dose-escalation phase.

In the dose-expansion phase, etrumadenant at RP2D in combination with zimberelimab may be assessed in participants with advanced clear-cell renal cell carcinoma (RCC) or metastatic castrate-resistant adenocarcinoma of the prostate (mCRPC).

Overall duration of treatment will depend on how well the treatment is tolerated. Treatment may continue until unacceptable toxicity or progressive disease or other reasons specified in the protocol.

Being tested
Etrumadenant, Zimberelimab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Breast Neoplasms, Colorectal Neoplasms, Melanoma, Urinary Bladder Neoplasms, Ovarian Neoplasms, Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EtrumadenantDrug

    Also called AB928

    Etrumadenant is an A2aR and A2bR antagonist.

  • ZimberelimabDrug

    Also called AB122

    Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

Study groups in NCT03629756
Study groupRoleWhat they receive
Dose EscalationExperimental3+3 design, including a DLT evaluation period. Etrumadenant RP2D will be determined in this part with escalating doses of oral etrumadenant in combination with a fixed dose of IV zimberelimab.
Receives: Drug: Etrumadenant; Drug: Zimberelimab
Dose Expansion-advanced clear-cell RCCExperimentalEtrumadenant at RP2D + zimberelimab
Receives: Drug: Etrumadenant; Drug: Zimberelimab
Dose Expansion-mCRPCExperimentalEtrumadenant at RP2D + zimberelimab
Receives: Drug: Etrumadenant; Drug: Zimberelimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of participants with Adverse Events

    Safety will be assessed by monitoring adverse events and clinically relevant changes in Eastern Cooperative Oncology Group (ECOG) performance status, 12 lead Electrocardiogram (ECG), vital signs, physical examination and clinical laboratory results.

    Measured: From first dose date to 90 days after the last dose (approximately 3 years)

  2. Percentage of participants who experience a Dose Limiting Toxicity

    Measured: From first study treatment administration through Day 28

Secondary outcomes (10)

  1. Etrumadenant Peak Serum Concentration: Cmax

    Measured: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)

  2. Zimberelimab Peak Serum Concentration: Cmax

    Measured: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)

  3. Etrumadenant Time of Peak Concentration: Tmax

    Measured: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)

  4. Zimberelimab Time of Peak Concentration: Tmax

    Measured: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)

  5. Percentage of participants with anti-drug antibodies to zimberelimab

    Measured: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), at end of treatment, and 30 and 90 days post last dose (approximately 7 months)

  6. Progression Free Survival (PFS)

    PFS as determined by Investigator according to Prostate Cancer Working Group 3 (PCWG3) for prostate adenocarcinoma and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for all other tumor types

    Measured: From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 1-3 years)

  7. Overall Survival (OS)

    OS as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types

    Measured: From study start of treatment up to death from any cause (approximately 1-3 years)

  8. Duration of Response (DOR)

    DOR as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types

    Measured: From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (approximately 1-3 years)

  9. Percentage of Participants with Disease Control

    Disease Control (complete response, partial response, or stable disease) for >6 months as determined by the Investigator per PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types

    Measured: From study enrolment until disease progression or loss of clinical benefit (approximately 1-3 years)

  10. Percentage of participants with Objective Response

    Objective Response as determined by Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types

    Measured: From study enrolment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1-3 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2018
  2. Study start24 Jul 2018
  3. Primary completion18 Aug 2021
  4. Study completion3 Sep 2021

Resources

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
3+3 Dose escalation design.
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03629756
Sponsor's protocol ID
ARC-5 (AB928CSP0005)
Status last verified
May 2024
First submitted
17 Jul 2018
Last updated
24 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan \[SAP\], Clinical Study Report \[CSR\]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. For more information, please visit our website.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Etrumadenant and Zimberelimab in people with Non-small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck, run by Arcus Biosciences, Inc. at 15 sites in 2 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 12 inclusion and 8 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: finished, as of the sponsor's last update on 24 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Australia. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Percentage of participants with Adverse Events (time frame: From first dose date to 90 days after the last dose (approximately 3 years)). The study lists 2 primary outcomes in all. 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 NCT03629756.

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 24 May 2024.

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