A Phase Ib, Open-Label, Dose-Escalation, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Efficacy Of Subcutaneous Glofitamab Following Obinutuzumab Pretreatment in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma.
Primary Objective:
To evaluate the safety and tolerability of glofitamab SC administration.
Secondary:
1. To characterize the PK profile of glofitamab SC administration.
2. To evaluate the preliminary efficacy of glofitamab given subcutaneously followed
by IV and/or SC administration.
3. To evaluate potential effects of ADAs.
4. To evaluate the relationship between glofitamab exposure and pharmacodynamic biomarkers.
5. To evaluate the preliminary efficacy of tocilizumab in ameliorating the symptoms of
severe CRS following glofitamab treatment.
Tocilizumab
Glofitamab
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Matthew Matasar
- Principal Investigator
Inclusion Criteria
- History or status of a histologically-confirmed hematological malignancy that is
expected to express CD19 and CD20; relapse after or failure to respond to at least
one prior treatment regimen; no available treatment options that are expected to
prolong survival (Part I and II); relapsed after or failed to respond to only one
prior systemic treatment regimen (Part III)
- Must have at least one measurable target lesion (>/= 1.5 cm) in its largest
dimension by computed tomography scan
- Able and willing to provide a fresh biopsy from a safely accessible site, per
Investigator's determination, providing the participant has more than one measurable
target lesion
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or
some participants in Part III
- Life expectancy of >/= 12 weeks
- Adverse events from prior anti-cancer therapy must have resolved to Grade
- Adequate liver, hematological, and renal function
- Negative test results for acute or chronic hepatitis B virus infection
- Negative test results for hepatitis C virus and HIV
- The contraception and abstinence requirements are intended to prevent exposure of an
embryo to the study treatment. The reliability of sexual abstinence for male and/or
female enrollment eligibility needs to be evaluated in relation to the duration of
the clinical study and the preferred and usual lifestyle of the participant.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation
methods) and withdrawal are not acceptable methods of preventing drug exposure
- Female participants: A female participant is eligible to participate if she is not
pregnant and not breastfeeding, and if at least one of the following applies: women
of non-childbearing potential (WONCBP); women of child bearing potential (WOCBP) who
agree to remain abstinent or use two highly effective contraceptive methods with a
failure rate of <1% per year during the treatment period and for at least 18 months
after obinutuzumab or 3.5 months after the last dose of englumafusp alfa, 2 months
after last dose of glofitamab, or 3 months after the last dose of tocilizumab,
whichever is longer. Examples of contraceptive methods with a failure rate of < 1%
per year include bilateral tubal occlusion/ ligation, male sexual partner who is
sterilized, established proper use of hormonal contraceptives that inhibit
ovulation, hormone-releasing intrauterine devices and copper intrauterine devices.
Hormonal contraceptive methods must be supplemented by a barrier method; have a
negative pregnancy test (blood) within the 7 days prior to the first study treatment
administration
- Male participants: During the treatment period and for at least 3 months after
obinutuzumab, or 3.5 months after the last dose of englumafusp alfa, 2 months after
the last dose of glofitamab, or 2 months after the last dose of tocilizumab
whichever is longer, agreement to: Remain abstinent or use contraceptive measures
such as a condom plus an additional contraceptive method that together result in a
failure rate of < 1% per year, with a partner who is a women of childbearing
potential. With pregnant female partner, remain abstinent or use contraceptive
measures such as a condom to avoid exposing the embryo; refrain from donating sperm
during this same period
Exclusion Criteria
- Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count
(ALC) or the presence of abnormal cells in the peripheral blood signifying
circulating lymphoma cells (for some participants in Part III, ALC only)
- Participants with acute bacterial, viral, or fungal infection at baseline, confirmed
by a positive blood culture within 72 hours prior to obinutuzumab infusion or by
clinical judgment in the absence of a positive blood culture
- Participants with known active infection, or reactivation of a latent infection,
whether bacterial, viral fungal, mycobacterial, or other pathogens (excluding fungal
infections of nail beds) or any major episode of infection requiring hospitalization
or treatment with IV antibiotics
- Pregnant or breast-feeding or intending to become pregnant during the study
- Prior treatment with systemic immunotherapeutic agents, including, but not limited
to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines or monoclonal
antibodies within 4 weeks or five half-lives of the drug, whichever is shorter,
before obinutuzumab infusion
- History of treatment-emergent immune-related AEs associated with prior
immunotherapeutic agents and auto-immune disease
- Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with
any other investigational or approved anti-cancer agent within 4 weeks or 5
half-lives of the drug, whichever is shorter, prior to obinutuzumab infusion
- Prior solid organ transplantation
- Prior allogeneic stem cell transplant (SCT) and prior chimeric antigen receptor
-T-cell therapy
- Autologous SCT within 100 days prior to obinutuzumab infusion
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
and confirmed progressive multifocal leukoencephalopathy
- Current or past history of central nervous system (CNS) lymphoma and CNS disease
- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results, including diabetes
mellitus, history of relevant pulmonary disorders and known autoimmune diseases
- Major surgery or significant traumatic injury < 28 days prior to the Gpt infusion or
anticipation of the need for major surgery during study treatment
- Participants with another invasive malignancy in the last 2 years
- Significant cardiovascular disease
- Administration of a live, attenuated vaccine within 4 weeks before Gpt infusion or
anticipation that such a live attenuated vaccine will be required during the study
- Received systemic immunosuppressive medications (including but not limited to
cyclohosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents) within two weeks prior to Gpt, with the exception of corticosteroid
treatment <=25 mg/day of prednisone or equivalent, however there must be
documentation that the participant was on a stable dose of at least a 2-week
duration prior to Gpt infusion. Inhaled and topical steroids are permitted
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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