This is an open-label, First-in-Human, dose escalation and dose expansion study of THOR-707
(Monotherapy and Combination Therapy) in adult subjects with advanced or metastatic solid
This is a First-in-Human, open-label, multiple ascending dose escalation and dose expansion
study of THOR-707 in adult subjects with advanced or metastatic solid tumors. The objectives
of the dose escalation phase are to identify the recommended phase 2 dose (RP2D) of THOR-707
as a monotherapy (Part 1) and in combination with a checkpoint inhibitor (Part 2); to
evaluate safety/tolerability of THOR-707; to evaluate anti-tumor activity of THOR-707; to
evaluate pharmacokinetics of THOR-707; and to evaluate various immunological biomarkers pre-
and post-treatment with THOR-707. The objectives of the dose expansion phase (Part 3) are to
further evaluate safety and anti-tumor activity of THOR-707 (administered at the RP2D) as a
monotherapy and in combination with a checkpoint inhibitor in select populations of patients
with advanced or metastatic solid tumors.
Key Inclusion Criteria:
- Measurable disease per RECIST v1.1.
- Life expectancy greater than or equal to 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate cardiovascular, hematological, liver, and renal function.
- Histologically or cytologically confirmed diagnosis of advanced and/or metastatic
solid tumors with at least one tumor lesion with location accessible to safely biopsy
per clinical judgment of the Investigator.
- Prior anti-cancer therapy is allowed as long as any treatment related toxicity is
resolved to an appropriate level.
- Females of childbearing potential and men who are not surgically sterile must agree to
use medically-accepted method of birth control during the study and for at least 3
months after last dose of treatment.
- [Females] Negative serum pregnancy test within 7 days prior to initiating study
treatment in premenopausal women and women less than 12 months after menopause.
- [Males] Agreement to refrain from donating or banking sperm during the treatment
period and for at least 3 months after last dose of study treatment.
Key Exclusion Criteria:
- Radiotherapy ≤ 14 days prior to first dose of study drug (palliative radiation or
stereotactic radiosurgery within 7 days prior to start of study treatment).
- Treated with systemic anti-cancer therapy or an investigational agent within 2 weeks
prior to start of study drug treatment (within 4 weeks for immunotherapy and tyrosine
kinase inhibitor therapy).
- Major surgery ≤ 30 days prior to first dose of study drug, or has not recovered to at
least Grade 1 from adverse effects from such procedure, or anticipation of the need
for major surgery during study treatment.
- Active autoimmune disease requiring systemic treatment within the past 3 months or
have a documented history of clinically severe autoimmune disease that requires
systemic steroids or immunosuppressive agents.
- Primary central nervous system (CNS) disease or leptomeningeal disease; known CNS
metastases unless treated, are asymptomatic, are without evidence of radiological
progression for at least 8 weeks, and have had no requirement for steroids or enzyme
inducing anticonvulsants in the last 14 days prior to Screening.
- Abnormal pulmonary function, including history of pneumonitis, active pneumonitis,
interstitial lung disease requiring the use of steroids, idiopathic pulmonary
fibrosis, confirmed pleural effusion, severe dyspnea at rest or requiring
supplementary oxygen therapy.
- History of allogenic or solid organ transplant.
- Known human immunodeficiency virus (HIV) infection or active infection with hepatitis
B or C.
- Clinically significant bleeding within 2 weeks prior to initial THOR-707 dose (e.g.,
gastrointestinal bleeding, intracranial hemorrhage).
- Prior diagnosis of deep vein thrombosis or pulmonary embolism within 3 months.
- Severe or unstable cardiac condition within 6 months prior to starting study
treatment, such as congestive heart failure (New York Heart Association Class III or
IV), cardiac bypass surgery or coronary artery stent placement, angioplasty, cardiac
ejection fraction below the lower limit of normal, unstable angina, medically
uncontrolled hypertension (e.g. ≥160 mm Hg systolic or ≥100 mm Hg diastolic),
uncontrolled cardiac arrhythmia requiring medication (≥ grade 2, according to NCI
CTCAE v5.0), or myocardial infarction.
- History of non-pharmacologically induced prolonged corrected QT interval determined
using Fridericia's formula (QTcF) > 480 milliseconds (msec).
- Known hypersensitivity to any components of THOR-707, PEG, pegylated drugs, or
checkpoint inhibitors for applicable cohorts.
- Active second malignancy, or history of previous malignancy that would impact the
assessment of any study endpoints. Subjects with non-melanomatous skin cancer or
cervical cancer that has been curatively surgically resected are eligible.
- Any serious medical condition (including pre-existing autoimmune disease or
inflammatory disorder), laboratory abnormality, psychiatric condition, or any other
significant or unstable concurrent medical illness that in the opinion of the
Investigator would preclude protocol therapy or would make the subject inappropriate
for the study.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 3 months
after the last dose of study treatment.
- Concurrent therapy with any other investigational agent, vaccine, or device.
Concomitant participation in observational studies is acceptable after Sponsor