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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03629756
• Other study ID #: ARC-5 (AB928CSP0005)
• Status: Completed
• Phase: Phase 1
• Start date: July 24, 2018
• Est. completion date: September 3, 2021

Study information

• Verified date: August 2023
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: September 3, 2021
• Est. primary completion date: August 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female participants = 18 years

2. Must have at least 1 measurable lesion per RECIST v1.1.

3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

4. Must have received standard of care, including potentially curative available therapies or interventions.

5. 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.

6. Adequate organ and marrow function

Dose escalation only:

7. 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:

8. 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.

9. 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.

10. 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.).

Exclusion Criteria:

1. Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product.

2. 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.

3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

4. 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.

5. 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.

6. 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.

7. 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;

8. 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.

Related Conditions & MeSH terms

• Bladder Cancer
• Breast Cancer
• Carcinoma
• Carcinoma, Merkel Cell
• Carcinoma, Renal Cell
• Castration-resistant Prostate Cancer
• Colorectal Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• GastroEsophageal Cancer
• Melanoma
• Merkel Cell Carcinoma
• Non-small Cell Lung Cancer
• Ovarian Cancer
• Renal Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck

Intervention

Drug:
• Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist.
• Zimberelimab
Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

Locations

Country	Name	City	State
Australia	Gallipoli Medical Research Foundation	Greenslopes	Queensland
Australia	St. George Private Hospital	Kogarah	New South Wales
Australia	Cabrini Health Limited	Malvern
United States	University of Michigan	Ann Arbor	Michigan
United States	Rocky Mountain Cancer Centers (Midtown)	Denver	Colorado
United States	Texas Oncology, P.A. - Fort Worth Cancer Center	Fort Worth	Texas
United States	Prisma Health	Greenville	South Carolina
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	QUEST Research Institute	Royal Oak	Michigan
United States	Texas Oncology, P.A. - San Antonio Medical Center	San Antonio	Texas
United States	Scottsdale Healthcare Hospitals dba HonorHealth	Scottsdale	Arizona
United States	Medical Oncology Associates dba Summit Cancer Centers	Spokane	Washington
United States	Texas Oncology, P.A. - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From first dose date to 90 days after the last dose (approximately 3 years)
Primary	Percentage of participants who experience a Dose Limiting Toxicity		From first study treatment administration through Day 28
Secondary	Etrumadenant Peak Serum Concentration: Cmax		Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Secondary	Zimberelimab Peak Serum Concentration: Cmax		Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Secondary	Etrumadenant Time of Peak Concentration: Tmax		Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Secondary	Zimberelimab Time of Peak Concentration: Tmax		Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Secondary	Percentage of participants with anti-drug antibodies to zimberelimab		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)
Secondary	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	From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 1-3 years)
Secondary	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	From study start of treatment up to death from any cause (approximately 1-3 years)
Secondary	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	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)
Secondary	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	From study enrolment until disease progression or loss of clinical benefit (approximately 1-3 years)
Secondary	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	From study enrolment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1-3 years)

External Links

•   ARC-5 - Lay Summary (English Version)