Phase 1/2 Study Of Intratumoral G100 With Or Without Pembrolizumab In Patients With Follicular Non-Hodgkin’s Lymphoma

  • STATUS
    Recruiting
  • sponsor
    Immune Design
Updated on 23 November 2020

Summary

Phase 1/2 Study Of Intratumoral G100 With Or Without Pembrolizumab In Patients With Follicular Non-Hodgkin’s Lymphoma

Description

This is a multi-center Phase 1/2 open label trial of G100 in patients with low grade NHL. G100 is composed of glucopyranosyl lipid A in a stable emulsion (GLA-SE) and is a potent TLR4 (toll-like receptor-4 agonist. In this study, G100 will be administered by direct injection (intratumorally) into tumors of low-grade NHL patients following 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 clinical efficacy of G100 will be examined alone or with pembrolizumab.

This study will have two phases. In Part 1, Dose Escalation, two sequentially enrolled cohorts of patients will be treated at one of 2 dose levels of G100 using a standard escalation design. This study will have two phases. In Part 1, Dose Escalation, two sequentially enrolled cohorts of patients 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 eligible. In Part 2, 2 groups of patients 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, patients with injectable tumors of 4 cm or greater would be enrolled and treated with a higher dose of G100.

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.

Study Contact Information:

Debi Kadoun
Phone: 253-428-8752
Email: dkadoun@nwmsonline.com

Linda Dhaene
Phone: 253-428-8753
Email: ldhaene@nwmsonlin.com

Details
Condition Adult Non-Hodgkin Lymphoma
Clinical Study IdentifierTX141261
SponsorImmune Design
Last Modified on23 November 2020

Eligibility

Yes No Not Sure

Inclusion Criteria

Follicular low grade NHL: either treatment naive or relapsed or refractory following at least one prior treatment. In Part 1 Dose Escalation only, in addition to follicular NHL, marginal zone B cell lymphomas: either treatment naive or relapsed or refractory follow at least one prior treatment
Tumor mass(es) accessible for intratumoral injection and are being considered for local radiation therapy and at least one additional site of disease outside the radiation field for assessment of distal (abscopal) response
≥ 18 years of age
Life expectancy of ≥ 6 months per the investigator
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
ECG without evidence of clinically significant arrhythmia or ischemia
If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use at least one highly effective or two effective contraceptive methods during the dosing period and for three months after last study treatment, or if receiving pembrolizumab, four months after last treatment
If male and sexually active with a FCBP, must agree to use highly effective contraception such as latex condom during the dosing period and for three months after last study treatment, or if receiving pembrolizumab, four months after last treatment

Exclusion Criteria

Cancer therapies, including chemotherapy, radiation (non-study regimen related), biologics or kinase inhibitors, G-CSF or GM-CSF within 4 weeks prior to the first scheduled G100 dose
Investigational therapy within 4 weeks prior to G100 dosing
Prior administration of other intratumoral immunotherapeutics
Inadequate organ function including
Marrow: Peripheral blood leukocyte count (WBC) < 3000/mm3, absolute neutrophil count ≤ 1500/mm3, platelets < 75000/mm3, or hemoglobin < 10 gm/dL
Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2.5 x Upper Limit of Normal (ULN), total serum bilirubin > 1.5 x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ≤3.0 mg/dL)
Renal: Creatinine > 1.5x ULN
Other: INR (prothrombin time ratio) or partial thromboplastin time (PTT) >1.5 x ULN
Significant immunosuppression from
Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic corticosteroids at any dose, or
Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine or conditions such as common variable hypogammaglobulinemia
Pregnant or nursing
Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
History of other cancer within 2 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ)
Recent (< 1 week ago) clinically significant infection, active tuberculosis or evidence of active hepatitis B, hepatitis C or HIV infection
Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease
Significant autoimmune disease, including active non-infectious pneumonitis, with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy
Psychiatric, other medical illness or other condition that in the opinion of the PI prevents compliance with study procedures or ability to provide valid informed consent
History of significant adverse or allergic reaction to any component of G100 including egg lecithin, and if enrolled in Part 2, anti-PD-1 antibodies
Use of anti-coagulant agents or history a significant bleeding diathesis. (If a superficial lymph node or subcutaneous mass is to be injected, patients on agents such as non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, or clopidogrel are eligible and these agents do not have to be withheld. For procedures with moderate or significant risk of bleeding, long-acting agents such as aspirin or clopidogrel should be discussed with the Medical Monitor and may need to be discontinued before G100 therapy
For patients enrolled in Part 2 with the potential to receive pembrolizumab
History of interstitial lung disease
Received a live virus vaccine within 30 days of planned study start
Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD.)
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in Merck MK-3475 clinical trials
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