A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies

Overview

About this study

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of AB308 in combination with zimberelimab (AB122) in participants with advanced malignancies.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  • Male or female participants ≥ 18 years of age (or age ≥ regionally approved age of consent for participation in investigational clinical studies) at the time of signing the informed consent.
  • Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    • Male and female participants will follow contraception guidelines. 

Disease-specific criteria for dose escalation (Parts A and B):

  • Participants may have any pathologically confirmed solid tumor type for which no standard of care therapy exists, or pathologically confirmed NHL who are refractory or have relapsed on prior chemotherapy regimen and who have not received or are unable to receive allogeneic stem cell transplant (ASCT). Prior autologous stem cell transplant is allowed, but not prior CAR-T therapy;
  • Participants may have received up to and including 5 lines of prior systemic anti-cancer therapies for advanced/recurrent and PD (an unlimited number of prior hormonal therapies) is allowed.

Disease-specific criteria for dose-expansion Cohort 1 (NSCLC):

  • Histologically confirmed, treatment naive, locally advanced or metastatic (stage IIIB ─ IV per AJCC version 8), squamous or non-squamous NSCLC; and
  • Documented high PD-L1 expression with a TPS ≥ 50% (TPS50) by an FDA-approved assay.

Disease-specific criteria for dose-expansion Cohort 2 (melanoma):

  • Histologically confirmed metastatic melanoma; and
  • Have received at least 1 line of prior systemic anticancer therapy (2L+); and
  • Have relapsed following prior PD-L1 therapy.

Disease-specific criteria for dose-expansion Cohort 3 (GI):

  • Histologically confirmed metastatic gastric, GEJ or esophageal cancer with a CPS ≥ 1 (CPS1) by an FDA-approved assay; and
  • Have received at least 1 line of chemotherapy (2L+); and
  • Have not received PD-L1 therapy.

Disease-specific criteria for dose-expansion Cohort 4 (Gyn):

  • Histologically confirmed recurrent or metastatic cervical cancer with CPS1 by an FDA-approved assay; and
  • Have received at least 1 line of chemotherapy (2L+); and
  • Have not received PD-L1 therapy.

Disease-specific criteria for dose-expansion Cohort 5 (DLBCL):

  • The following histologically confirmed DLBCL subtypes as defined per 2016 WHO criteria (Swerdlow, 2016):
    • DLBCL, not otherwise specified (NOS);
    • Germinal center B-cell type (GCB);
    • Activated B-cell type (ABC/non-GCB);
    • Epstein-barr virus (EBV+);
    • Human herpes virus-8 (HHV8+);
    • Primary cutaneous DLBCL;
    • DLBCL with chronic inflammation;
    • High-grade B-cell lymphoma, NOS with MYC and BCL2 and/or BCL6 rearrangements (ie, double-triple-hit lymphomas);
    • Must have received at least two prior lines of systemic therapy (3L+); and
    • Have not received or are unable to receive ASCT. Prior autologous stem cell transplant and CAR-T therapy are allowed.

Disease-specific criteria for dose-expansion Cohort 5 (MM):

  • Documented MM as defined by monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy-proven plasmacytoma;
  • Relapsed or refractory MM after having received at least 3 prior lines of therapy (4L+) that include a proteasome inhibitor, an immunomodulatory imide drug (IMiD), and an anti-CD38 monoclonal antibody and for which no established therapy for MM is appropriate and available, or intolerant to established therapies;
  • Have not received or are unable to receive ASCT. Prior autologous stem cell transplant and CAR-T therapy are allowed;
  • Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) guidance (Version 1.1) for solid tumor indications, or 1 measurable lesion per Lugano Classification criteria for NHL. The measurable lesion must be outside of a radiation field if the participant received prior radiation.
  • Participants with R/R MM must have measurable disease as defined by at least 1 of the criteria below:
    • Serum M-protein ≥1 g/dL;
    • Urine M-protein ≥ 200 mg/24 h;
    • Serum free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is abnormal.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  • Confirmation that the most recent archival tissue sample (FFPE block or freshly cut slides) is available that is representative of the cancer under investigation and adequate for central lab testing of PD-L1 expression by immunohistochemistry. If freshly cut slides or FFPE block is not available, archival unstained slides < 12 months old may be used. If archival tissue is not available as described above, participants will be requested to consent to undergo a fresh biopsy of a tumor lesion not previously irradiated (tumors progressing in a prior site of radiation may be considered after sponsor consultation). The biopsy must not put participants at undue risk and the procedure must not be more invasive than a core biopsy as documented in the medical record by the investigator.
  • Participants who received prior immunotherapy will be allowed to participate in this study if:
    • Any Grade 1 to 2 immune-related AE (irAE) that occurred during treatment with antiPD-1 or anti-PD-L1 therapy improved to ≤ Grade 1 and/or is stably controlled on repletion hormonal therapy or physiologic doses of corticosteroids (not to exceed 10 mg/day prednisone equivalent). Steroid therapy and/or immunosuppressive therapy for irAEs has been discontinued for > 30 days prior to study enrollment;
    • Grade 3 irAEs of laboratory abnormalities (asymptomatic) improved to ≤ Grade 1 or baseline and steroid therapy and/or immunosuppressive therapy for irAEs has been discontinued for > 30 days prior to study enrollment.
  • Participants who harbor genomic aberrations for which FDA-approved targeted therapy exists must have received such therapy prior to enrollment, unless such therapy is deemed inappropriate in the opinion of the investigator (e.g., EGFR+/ALK+).
  • Participants with previously treated brain or meningeal metastases must meet the following criteria:
  • No evidence of progression by magnetic resonance imaging (MRI) for at least 4 weeks prior to the first dose.
  • Neurologic symptoms returned to baseline.
  • Carcinomatous meningitis, which is excluded regardless of clinical stability.
  • Prior radiation therapy must have been completed as follows:
  • Prior systemic radiation or whole brain radiation at least 4 weeks before investigational product administration.
  • Prior focal radiotherapy at least 2 weeks before investigational product administration.
  • No radiopharmaceuticals (e.g., strontium, samarium) may have been administered.
  • Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or hepatitis C qualitative RNA [qualitative]), and HIV-1 and HIV-2 antibody at screening.
    • Note: Participants with treated hepatitis B and/or C with no evidence of active infection may be enrolled.
  • Adequate organ and marrow function, as defined below:
    • Neutrophils ≥ 1500/μL (in absence of growth factor support);
    • Platelets ≥ 100 × 10^3/μL;
    • Hemoglobin ≥ 9.0 g/dL;
    • Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance ≥ 30 mL/min as determined by Cockcroft-Gault equation (Cockcroft, 1976);
    • AST ≤ 2.5 × ULN without hepatic metastasis and ≤ 5 × ULN with hepatic metastasis;
    • ALT ≤ 2.5 × ULN without hepatic metastasis and ≤ 5 × ULN with hepatic metastasis;
    • Bilirubin ≤ 2 × ULN (except participants with Gilbert’s syndrome who must have total bilirubin < 3.0 mg/dL);
    • Platelets ≥ 75 × 10^3/μL, neutrophils ≥ 1000/μL, and hemoglobin ≥ 8 g/dL (dose-expansion Cohort 5 only).

Exclusion Criteria:

  • Use of any live vaccines against infectious diseases (e.g., 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 (e.g., 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.
  • History of trauma or major surgery within 28 days prior to the first dose of investigational product.
    • Note that placement of central venous access catheter (e.g., port or similar) is not considered a major surgical procedure.
  • Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor-α agents) administered at > 10 mg/day prednisone or equivalent within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment, with the following exceptions:
    • Participants who received low dose (≤ 10 mg/day prednisone or equivalent), systemic immunosuppressant medications or a 1-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after medical monitor approval has been obtained;
    • Participants who received mineralocorticoids (e.g., fludrocortisone), inhaled or intranasal corticosteroids for chronic obstructive pulmonary disease or asthma, or low dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study after medical monitor approval has been obtained.
  • Participants with NHL who have current or history of CNS lymphoma, or current eligibility for ASCT.
  • Participants with R/R MM with primary or secondary plasma cell leukemia, current or history of CNS involvement or received prior ASCT.
  • Prior treatment with an anti-TIGIT monoclonal antibody.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Positive serum pregnancy test at screening and prior to dosing on Cycle 1 Day 1 (WOCBP only).
  • 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 AB308 in combination with zimberelimab.
  • Any active or documented history of autoimmune disease including, but not limited to, inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of study treatment, except for the following:
    • Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders such as vitiligo, or alopecia not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger;
    • Endocrinopathies where the participant is stable on hormone replacement therapy;
    • History of Hashimoto syndrome within 3 years of the first of study treatment that resolved to hypothyroidism alone.
  • 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.
  • Prior chemotherapy, targeted small-molecule therapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer), or biologic agents, or use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is shorter) before investigational product administration.
  • Adverse events from prior anti-cancer therapy that have not improved to baseline or Grade 1 (excluding irAEs, ≤ Grade 2 alopecia, or ≤ Grade 2 neuropathy).
  • History of discontinuation of immunotherapy (e.g., anti-PD-1, anti-PD-L1, or anti CTLA-1 antibody) for ≥ CTCAE Grade 3 irAEs.

Eligibility last updated 3/29/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Thanh Ho, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mahesh Seetharam, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Sikander Ailawadhi, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
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