Zimberelimab (AB122) With TIGIT Inhibitor Domvanalimab (AB154) in PD-1 Relapsed/Refractory Melanoma

  • STATUS
    Recruiting
  • End date
    Jan 29, 2028
  • participants needed
    26
  • sponsor
    Diwakar Davar
Updated on 29 April 2022
measurable disease
anticoagulants
direct bilirubin
melanoma skin
BRAF
anticoagulant therapy
neutrophil count
thromboplastin
mek inhibitor
immunomodulators
immunologic adjuvant
cytotoxic t-lymphocyte antigen 4
malignant melanoma of skin

Summary

The main goal of this study is to establish the proportion of patients with objective response to zimberelimab/domvanalimab in PD-1 R/R melanoma patients.

Description

This is a single-arm two-stage phase II study of PD-1 inhibitor zimberelimab (AB122) in combination with TIGIT inhibitor domvanalimab (AB154) in advanced melanoma patients who have failed PD-1 inhibitor therapy.

Patients will undergo a 28-day screening evaluation consisting of systemic staging scans, tumor biopsy, and blood studies to confirm suitability. Once enrolled, patients will receive zimberelimab 360 mg every 3 weeks (Q3W) and domvanalimab 15 mg/kg Q3W. Patients will undergo restaging scans at W9 following 3 cycles of therapy with response assessed using RECIST v1.1 and iRECIST. Following restaging scans, patients with response will continue to receive zimberelimab and domvanalimab till disease progression, intolerable toxicity or for up to 24 months.

Details
Condition Melanoma
Treatment Zimberelimab, Domvanalimab
Clinical Study IdentifierNCT05130177
SponsorDiwakar Davar
Last Modified on29 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of cutaneous melanoma (or unknown primary) will be enrolled in this study
Male participants: A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies
Not a woman of childbearing potential (WOCBP); OR
A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment
Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered
either as monotherapy or in combination with other checkpoint inhibitors or
other therapies. PD-1 treatment progression is defined by meeting all of the
following
criteria
Has received at least 2 doses of an approved anti-PD-1/L1 mAb
Participants who progressed on/within 3 months of adjuvant therapy with anti-PD-(L)1 inhibitor will be allowed
Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression (as defined in 4.c)
Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb
Progressive disease as determined above. This determination is made by the treating investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of PD. Anti-PD/L1 mAb need not be the most recent line of therapy administered
Prior treatment with an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
antibody is allowed but not required
Prior treatment with BRAF/MEK inhibitor therapy (if BRAF mutated) is allowed but not required
The participant provides written informed consent for the trial
Presence of measurable disease based on RECIST 1.1
Patients need to have at least one measurable lesion and a separate lesion for biopsy. Patients with only 1 lesion may be enrolled after discussion with Sponsor-Investigator
Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Able to provide newly obtained core or excisional biopsy of a tumor lesion not
previously irradiated to undergo tumor biopsy (core, punch, incisional or
excisional)
\--- Biopsy must meet minimal sampling criteria
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed at screening prior to the first dose of study intervention
Have adequate organ function as defined below. Specimens must be collected within 28 days prior to the start of study intervention
Absolute neutrophil count (ANC) ≥1500/µL
Platelets ≥100 000/µL
Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks)
Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN (Creatinine clearance (CrCl) should be calculated per institutional standard)
Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
International normalized ratio (INR) OR prothrombin time (PT) and Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria

Receipt of prior agent(s) targeting components of the TIGIT/CD226 pathway including but not limited to CD226, TIGIT, PVR/CD155 and CD112
Diagnosis of non-cutaneous melanoma histologies including mucosal melanoma, ocular/choroidal melanoma, acral-lentiginous melanoma
Diagnosis of immunodeficiency, immunosuppression and/or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Prior chemotherapy, targeted therapy, and/or small molecule therapy within 2 weeks (or 4 half lives) prior to study Day 1
Patients who have not recovered (i.e., ≤Grade 1 or at baseline or ≤Grade 2 endocrinopathy) from adverse events (AEs) due to a previously administered agent
Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
\--- A 2-week washout is permitted for palliative radiation (≤2 weeks of
radiotherapy) to non-CNS disease
A WOCBP who has a positive urine pregnancy test at Screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Has received a live vaccine within 30 days prior to the first dose of study drug
Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine
Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form
of immunosuppressive therapy within 14 days prior to the first dose of study
drug
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
\--- Note: Replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency
etc.) is not considered a form of systemic treatment and is allowed
Concurrent non-hematologic malignancy within 3 years of data of first planned dose of therapy except for tumors with a negligible risk of metastasis and/or death as defined
below
Adequately treated non-invasive malignancies including but not limited to melanoma in situ (MIS), cutaneous squamous cell carcinoma (cSCC), in situ cSCC, basal cell carcinoma (BCC), CIS of cervix, or DCIS/LCIS of breast
Low-risk early-stage prostate adenocarcinoma (T1-T2a N0 M0 and Gleason score ≤6 and PSA ≤10 ng/mL) for which the management plan is active surveillance, or prostate adenocarcinoma with biochemical-only recurrence with documented PSA doubling time of > 12 months for which the management plan is active surveillance
Indolent hematologic malignancies for which the management plan is active surveillance including but not limited to CLL/indolent lymphoma. Patients with high-risk hematologic malignancies (CML, ALL, AML, Hodgkin's or non-Hodgkin's lymphoma) are excluded even if the management plan is active surveillance
Active (i.e., symptomatic or growing) central nervous system (CNS) metastases
Note: Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during Screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
Patients with leptomeningeal disease are excluded
Has severe hypersensitivity (≥Grade 3) to anti-PD(L)1 inhibitor
Has a systemic disease that requires systemic pharmacologic doses of corticosteroids greater than 10 mg daily prednisone (or equivalent)
Note: Participants who are currently receiving steroids at a dose of ≤10 mg daily do not need to discontinue steroids prior to enrollment
Note: Participants that require topical, ophthalmologic, injected and/or inhalational steroids are not excluded from the study
Note: Participants with hypothyroidism stable on hormone replacement or Sjogren's syndrome are not excluded from the study
Note: Participants who require active immunosuppression (greater than steroid dose discussed above) for any reason are excluded from the study
Has a history of interstitial lung disease or active, non-infectious pneumonitis that
required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has a known history of Human Immunodeficiency Virus (HIV) infection
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) and/or known active Hepatitis C virus (defined as anti-HCV reactive) infection
Patients with treated Hepatitis B/C with no evidence of active infection may be enrolled
Patients with a history of Hepatitis B and/or C who have been treated with curative intent may be enrolled if there is no evidence of active infection (Hepatitis B: negative HBsAg, Hepatitis C: undetectable HCV viral load)
Has a known history of active TB (Bacillus Tuberculosis)
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
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 Screening visit through 120 days after the last dose of trial treatment
Has had an allogenic tissue/solid organ transplant
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