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A Study to Evaluate Immunotherapy Combinations in Participants With Gastrointestinal Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03720678
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : March 31, 2020
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Brief Summary:
This is a Phase 1/1b, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of AB928 in combination with mFOLFOX in participants with advanced metastatic gastroesophageal Cancer (GEC) or colorectal cancer (CRC).

Condition or disease Intervention/treatment Phase
GastroEsophageal Cancer Colorectal Cancer Drug: AB928 Drug: mFOLFOX Phase 1

Detailed Description:

In the dose escalation phase, escalating doses of AB928 in combination with mFOLFOX at standard doses will be assessed in participants with advanced metastatic GEC or CRC. Eligible participants will receive oral administration of AB928 as well as IV infusion of mFOLFOX. The recommended dose for expansion (RDE) of AB928 will be determined upon completion of the dose-escalation phase.

In the dose expansion phase, AB928 at the RDE in combination with mFOLFOX at standard doses may be assessed in participants with advanced metastatic GEC or CRC.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 98 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Gastrointestinal Malignancies
Actual Study Start Date : October 15, 2018
Estimated Primary Completion Date : July 30, 2020
Estimated Study Completion Date : July 30, 2021

Arm Intervention/treatment
Experimental: Dose Escalation
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The RDE of AB928 will be determined in this part with escalating doses of AB928 in combination with the standard mFOLFOX chemotherapy regimen in participants with gastroesophageal or colorectal cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist.

Drug: mFOLFOX
Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen

Experimental: Dose Expansion-GE
The RDE of AB928 will be determined from the dose escalation part. AB928 will be given in combination with the standard mFOLFOX chemotherapy regimen in participants with gastroesophageal cancer
Drug: AB928
AB928 is an A2aR and A2bR antagonist.

Drug: mFOLFOX
Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen

Experimental: Dose Expansion-CRC
The RDE of AB928 will be determined from the dose escalation part. AB928 will be given in combination with the standard mFOLFOX chemotherapy regimen in participants with colorectal cancer
Drug: AB928
AB928 is an A2aR and A2bR antagonist.

Drug: mFOLFOX
Oxaliplatin, Leucovorin and 5-fluorouracil given as part of standard mFOLFOX chemotherapy regimen




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) [ Time Frame: From first dose date to 90 days after the last dose (Approximately 1 year) ]
  2. Incidence of dose-limiting toxicities (DLTs) during dose escalation phase [ Time Frame: From first dose date to 28 days after the first dose ]

Secondary Outcome Measures :
  1. Plasma concentration of AB928 [ Time Frame: Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (2 months), at end of treatment and 30 days post end of treatment (i.e. in total approximately 3 months) ]
  2. Percentage of participants with Objective Response as determined by Investigator according to RECIST v1.1 [ Time Frame: From study enrollment until participation discontinuation, first occurence of progressive disease, or death from any cause, whichever occurs frist (approximately 3-5 years) ]
  3. Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1 [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years) ]
  4. Duration of Response as determined by the Investigator according to RECIST v1.1 [ Time Frame: From the date of first occurence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years) ]
  5. Progression Free Survival (PFS) as determined by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: From start of treatment up to first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years) ]
  6. Overall Survival (OS) as determined by the Investigator according to RECIST v1.1 [ Time Frame: From start of treatment up to death from any cause (up to approximately 3-5 years) ]
  7. Receptor Occupancy in peripheral blood [ Time Frame: Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (2 months), at end of treatment and 30 days after end of treatment (in total approximately 3 months). Each Cycle is 28 days. ]
  8. T-cell immunophenotyping in peripheral blood [ Time Frame: Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (2 months), at end of treatment and 30 days after end of treatment (in total approximately 3 months). Each Cycle is 28 days. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants ≥ 18 years
  2. Histologically confirmed gastroesophageal cancer or colorectal cancer that is metastatic, advanced or recurrent with progression
  3. Participants for whom mFOLFOX is considered appropriate therapy
  4. Must have at least 1 measurable lesion per RECIST v1.1.
  5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  6. Must have received standard of care, including potentially curative available therapies or interventions.
  7. Confirm that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor lesion must be obtained.
  8. Adequate organ and marrow function

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. Untreated or symptomatic CNS disease
  5. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with screening visit through 30 days after the last dose of AB928 in combination with mFOLFOX.
  6. Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.

    1. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
    2. Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study.
  7. Prior malignancy active within the previous 2 years 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.
  8. Oxaliplatin-based therapy as the most recent regimen prior to enrolling in the study, except if prior oxaliplatin-based therapy was received as the most recent regimen in the adjuvant setting and completed ≥ 6 months prior to study enrollment.
  9. Prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 4 weeks prior to Day 1 or has not recovered (ie, ≥ Grade 1 or baseline) from AEs due to a previously administered agent, except ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy and other AEs considered not clinically significant by the Medical Monitor and Investigator.
  10. Use of other investigational drugs (drugs not marketed for any indication) within 28 days of investigational product administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03720678


Contacts
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Contact: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com

Locations
Show Show 24 study locations
Sponsors and Collaborators
Arcus Biosciences, Inc.
Investigators
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Study Director: Medical Director Arcus Biosciences, Inc.

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Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT03720678    
Other Study ID Numbers: AB928CSP0003
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: March 31, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases