Follicular Low Grade Non-Hodgkin's Lymphoma Clinical Trial
Official title:
Phase 1/2 Study of Intratumoral G100 With Or Without Pembrolizumab or Rituximab In Patients With Follicular Non-Hodgkin's Lymphoma
This is a Phase 1/2 open label trial of G100 in participants with low grade Non-Hodgkin's Lymphoma (NHL). G100 is composed of glucopranosyl lipid A in a stable emulsion and is a potent TLR4 (toll-like receptor-4) agonist. G100 will be administered by direct injection (intratumorally) into tumors of low grade NHL with or without standard low dose radiation therapy. Preclinical models and clinical studies in other cancers such as Merkel cell carcinoma have demonstrated that G100 administered in this manner can alter the tumor microenvironment, activate dendritic cells, T cells and other immune cells and induce systemic anti-tumor immune responses. In this trial, the safety, immunogenicity, and preliminary clinical efficacy of G100 will be examined alone or with pembrolizumab.
This is a multi-center Phase 1/2 open label trial of intratumoral G100 in participants with
low grade NHL. Eligible participants with NHL will be enrolled and receive G100 to an
accessible tumor mass. Clinical response will be evaluated in the injected tumor and systemic
(abscopal) responses will be evaluated in distal areas involved with tumor.
The study will be conducted in 5 parts. In Part 1, Dose Escalation, 2 sequentially enrolled
cohorts of participants will be treated at one of 2 dose levels of G100 using a standard
escalation design. In this portion of the study, both follicular and marginal zone NHL will
be eligible. In Part 2, 2 groups of participants with follicular NHL may be examined. One
group will be randomly assigned to receive either single agent G100 intratumorally at the
maximum safe dose determined in Part 1 following local radiation or will receive the same
treatment regimen sequentially administered with pembrolizumab. A second treatment group may
be explored if the safety profile in Part 1 is acceptable. In this optional group,
participants with injectable tumors of 4 cm or greater would be enrolled and treated with a
higher dose of G100. In Part 3, expansion of a higher dose (20µg of G100) in participants
with follicular NHL will be enrolled to receive local radiation therapy and intratumoral
G100. In Part 4, Dose Escalation and Expansion, a dose of 20µg of G100 will be examined as a
treatment of 1 or more tumors (up to 4) with pembrolizumab in order to establish safety and
examine clinical and biomarker responses in participants receiving increasing total systemic
doses of G100 and Part 5, will evaluate standard induction therapy with rituximab (anti-CD20)
in combination of escalating doses of intratumoral G100 in single tumors.
The primary goal of this study is to determine the safety and tolerability of different doses
of G100 when administered by intratumoral injection. The development of anti-tumor immune
responses and preliminary evidence of clinical responses in local and distal tumor sites will
also be examined.
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