The purpose of this study is to test the safety and tolerability of 2141-V11 in people who
have cancer that does not respond to standard treatment and who have skin lesions (skin
tumors) associated with their cancer. The study will also test how the body processes and
responds to 2141-V11, and if the study drug has cancer fighting activity in people. The study
drug activates a naturally occurring protein called CD40. By activating CD40, cells of the
immune system are better able to identify and kill cancer cells.
We are testing if injection of 2141-V11 into metastasis to the skin will be safe and well
tolerated, and may result in immune activation in patients with solid tumors that have
metastasis to the skin.
This is a Phase 1 open label, dose-escalation study evaluating the safety, pharmacokinetics,
pharmacodynamics, immunogenicity, and efficacy of the Fc-engineered variant 2141-V11 in
patients with previously treated relapsed or refractory solid tumors and locally advanced or
metastatic solid tumors to the skin amenable to intratumoral injection.
There are two parts to the study: a dose-finding stage (Part I), and a dose expansion stage
(Part II). Both Part I and Part II of the study will include patients with locally advanced
or metastatic cancers of the skin which are not amenable to standard treatment.
A traditional 3 + 3 dose escalation design will be used (Part I). Successive cohorts of
participants (3 participants/cohort) will be started on a fixed dose intratumoral injection
of 2141V11 at the dose assigned to their cohort. The study drug, 2141-V11, will be dosed once
every 3 weeks. The study drug is administered in cycles.
The first group of study participants in Part I will receive the lowest dose of study drug.
The next group of study participants will receive the next higher dose. This dosing scheme
continues until the maximum tolerated dose is determined. The maximum tolerated dose (MTD)
will be defined as 1 dose level below the dose in which DLTs are observed in >33% of the
Participants in Part II of the study will receive the MTD determined from Part 1 (dose
escalation) of the study. Part II participants in the study will also receive two
vaccinations (KLH and tetanus) to allow monitoring of their immune function.
Participants in both Part I and II can continue to receive cycles of study drug at their
assigned dose if they do not experience progression of disease, a serious adverse event, and
the study is ongoing.
1. Age > 18 years old
2. Must have measurable or evaluable metastatic disease (at least more than 1 lesion) as
evidenced by physical exam or imaging
3. Must have an identifiable metastatic lesion of the skin or subcutaneous tissue
amenable to intratumoral injection. This includes all solid tumors as well as
metastatic melanoma and/or melanoma with in-transit metastases.
4. ECOG performance status < 1
5. Histologically confirmed diagnosis of refractory or relapsed metastatic disease
6. Must have the ability to comply with the collection of tumor and skin biopsies, and
tumors must be accessible for biopsy.
7. Required values for screening laboratory tests:
1. Absolute neutrophil count (ANC) > 1000/mm3 independent of growth factor support
2. Platelets > 75,000/mm3
3. Hemoglobin > 8 g/dl
4. Creatinine clearance > 40 ml/min for the dose-escalation phase, >25 ml/min in
dose expansion phase (if safety data from dose escalation indicate this is
5. AST/ALT < 3 x ULN
6. Bilirubin < 1.5 x ULN (except for participants with Gilbert's Syndrome or of
8. Patients must have refractory or relapsed disease and have must have exhausted all
standard-of-care therapy for their disease
9. Must be at least 4 weeks since treatment with standard or investigational
chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, and recovered
from any clinically significant toxicity experienced during treatment.
10. If sexually active male or female and participating in sexual activity that could lead
to pregnancy, agrees to use two effective methods of contraception (i.e. condom with
spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based
contraceptive with condom). For females, these restrictions apply for 1 month after
the last dose of study drug. For males, these restrictions apply for 3 months after
the last dose of study drug. Men must agree not to donate sperm during and after the
study g. Female study participants of reproductive potential are defined as
pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy,
bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered
menopausal if they have not had a menses for at least 12 months and have a FSH of
greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for
24 consecutive months.
11. Women of childbearing potential must have a negative beta-human chorionic gonadotropin
(hCG) pregnancy test at screening, as well as a negative pregnancy test prior to each
12. Life expectancy greater than 16 weeks (should be evaluated by a prognostic score,
e.g., Roya Marsden score)
13. Able to comply with the treatment schedule as determined by the participant and the
1. Concurrent anticancer therapy including investigational agents. This includes topical
2. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic
organizing pneumonia), risk of pulmonary toxicity, or evidence of active pneumonitis
on screening chest CT scan
3. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
4. Patients with active hepatitis B (defined as having a positive hepatitis B surface
antigen (HBsAg) test at screening
5. Patients with past/resolved hepatitis B virus (HBV) infection (defined as having a
negative HBsAg and a positive antibody to hepatitis B core antigen antibody test) are
eligible only if polymerase chain reaction is negative for HBV RNA. HBV DNA must be
obtained in these patients prior to Cycle 1, Day 1.
6. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
7. Increased corrected QT (QTc) interval (QTc > 470 ms), patients with baseline resting
bradycardia < 45 bpm, or baseline resting tachycardia > 100 bpm
8. Has spinal cord compression not definitively treated with surgery and/or radiation or
previously diagnosed and treated spinal cord compression without evidence that disease
has been clinically stable for > 2 weeks prior to screening
9. Vaccinated with live, attenuated viral vaccines within 4 weeks of enrollment
10. Known history of human immunodeficiency virus (HIV) or any uncontrolled active
11. Major surgery or a wound that has not fully healed within 4 weeks of enrollment.
12. Treatment with an immunosuppressive regimen of corticosteroids or other
immunosuppressive medication (e.g., methotrexate, rapamycin) within 30 days of study
treatment. Note: patients with adrenal insufficiency may take up to 5 mg of prednisone
or equivalent daily. Topical and inhaled corticosteroids in standard doses are allowed
13. Severe infections within 4 weeks prior to Cycle 1, Day 1, including, but not limited
to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
14. Signs and symptoms of infection within 2 weeks prior to Cycle 1, Day 1
15. Any investigational therapy within 28 days prior to initiation of study treatment.
This includes topical or injected agents
16. Significant cardiovascular disease (i.e., NYHA class 3 congestive heart failure;
myocardial infarction within the past 6 months; unstable angina; coronary angioplasty
within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias
17. Autoimmune disease including systemic lupus erythematosus, rheumatoid arthritis,
multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, history of
uveitis or other autoimmune disease if clinically significant
18. Untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI)
evaluation during screening or prior radiographic assessments. Patients with
radiographically stable, asymptomatic previously irradiated lesions are eligible
provided patient is > 4 weeks beyond completion of cranial irradiation and > 3 weeks
of corticosteroid therapy.
19. Known history of leptomeningeal leptomeningeal disease, patients with metastases to
the brain stem, midbrain, pons, or medulla, and patients with metastases with 10 mm of
the optic apparatus (optic nerve and chiasm) will be excluded from the study
20. Requires anticoagulation with warfarin or equivalent vitamin K antagonists
21. Has had a pulmonary embolism or any other thromboembolic event within 6 months prior
to study entry
22. Any approved anti-cancer therapy, including chemotherapy, immunotherapy or hormonal
therapy, within 4 weeks prior to initiation of study treatment, with the following
1. Hormone-replacement therapy or oral contraceptives
2. Tyrosine kinase inhibitors (TKIs) that have been discontinued > 7 days prior to
Cycle 1, Day 1; screening scans must be obtained after discontinuation of prior
23. Prior toxicities from previous cancer therapy, including checkpoint inhibition, that
have not regressed to Grade < 1 severity (NCI CTCAE v4.03, or later versions) within
28 days before Cycle 1, Day 1, with the exception of alopecia
24. Active hepatitis C are excluded. Patients positive for hepatitis C virus (HCV)
antibody are eligible only if polymerase chain reaction is negative for HCV RNA
25. Any surgical procedure within less than 14 days of the first receipt of study drug.
Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of the
need for a major surgical procedure during the study other than for diagnosis.
26. Pregnant or breast feeding
27. Active infection or with a fever >38.5 degrees C within 3 days prior to the first
28. Any medical history, including laboratory results, deemed by the investigator to be
likely to interfere with their participation in the study, or to interfere with the
interpretation of the results, or any social condition that, in the opinion of the
Investigator, might pose additional risk to the participant or confound the results of