Clinical trial NCT03629756: A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Squamous Cell Carcinoma of the Head and Neck
Breast Cancer
Colorectal Cancer
Melanoma
Bladder Cancer
Ovarian Cancer
Endometrial Cancer
Merkel Cell Carcinoma
GastroEsophageal Cancer
Renal Cell Carcinoma
Castration-resistant Prostate Cancer
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 Dose escalation design.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of participants with Adverse Events
timeFrame: From first dose date to 90 days after the last dose (approximately 3 years)
measure: Percentage of participants who experience a Dose Limiting Toxicity
timeFrame: From first study treatment administration through Day 28
Secondary outcomes:
measure: Etrumadenant Peak Serum Concentration: Cmax
timeFrame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
measure: Zimberelimab Peak Serum Concentration: Cmax
timeFrame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
measure: Etrumadenant Time of Peak Concentration: Tmax
timeFrame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
measure: Zimberelimab Time of Peak Concentration: Tmax
timeFrame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
measure: Percentage of participants with anti-drug antibodies to zimberelimab
timeFrame: 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)
measure: Progression Free Survival (PFS)
timeFrame: From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 1-3 years)
measure: Overall Survival (OS)
timeFrame: From study start of treatment up to death from any cause (approximately 1-3 years)
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Percentage of Participants with Disease Control
timeFrame: From study enrolment until disease progression or loss of clinical benefit (approximately 1-3 years)
measure: Percentage of participants with Objective Response
timeFrame: From study enrolment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1-3 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals dba HonorHealth
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers (Midtown)
state: Colorado
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Royal Oak
country: United States
facility: QUEST Research Institute
state: Michigan
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Fort Worth
country: United States
facility: Texas Oncology, P.A. - Fort Worth Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology, P.A. - San Antonio Medical Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Tyler
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates dba Summit Cancer Centers
state: Washington
city: Kogarah
country: Australia
facility: St. George Private Hospital
state: New South Wales
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Foundation
state: Queensland
city: Malvern
country: Australia
facility: Cabrini Health Limited
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: