An Open-Label, Multicenter Phase 1/2 Dose Escalation and Expansion Study of THOR-707 as a Single Agent and as a Combination Therapy in Adult Subjects With Advanced or Metastatic Solid Tumors.
Study Identifier:
TCD16843
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Terminated/Withdrawn
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Study Summary
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 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.
To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of THOR-707 in patients with advanced or metastatic solid tumors.
To define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of THOR-707 as single agent and in combination with a PD-1 inhibitor; and to evaluate the overall safety and tolerability as well as, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity
The study will be conducted in 3 parts:
Part 1: will evaluate THOR-707 as a single agent across different dosing schedules (e.g., dosing every 2 weeks [Q2W] or 3 weeks [Q3W]).
Part 2: will evaluate THOR-707 (Q3W) in combination with a PD-1 inhibitor.
Part 3: Dose expansion will begin after the RP2D for THOR-707 as a single agent or in combination with a checkpoint inhibitor has been determined and will enroll selected populations (e.g., specific tumor types, treatment history, and/or biomarker profile).
Key objectives included assessments of safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD).
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Terminated/Withdrawn
Requirements information
Inclusion criteria
- Measurable disease per RECIST v1.1. For Cohorts G, E, F, and H participants must have at least 1 (Cohort G) or 2 measurable lesions (Cohorts E, F, and H) to safely perform mandatory pre & on-treatment biopsy.
- Life expectancy greater than or equal to 12 weeks.
- For Part 2 exclusively: While it is highly preferred to enroll subjects who are naïve to PD-1 inhibitors into a Part 2 dose escalation cohort, this is not an enrollment requirement. However, subjects who enroll into a Part 2 safety expansion cohort must be naïve to PD-1 inhibitors. If such subject is unable to meet this requirement but otherwise remains a good candidate for study enrollment, the Investigator should discuss with the Sponsor whether the subject may be enrolled.
- 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.
- Caution: Cohort D only patients with KRAS mutant colon cancer have not typically benefitted from the addition of cetuximab in earlier lines of therapy.
- Caution: Cohorts E & F enrollment will include only patients with tumors for which anti-PD(L)1 as single agent or in combination treatments are approved.
- Caution: For Cohort H, the participant must have received at least one prior line of therapy for metastatic melanoma and/or does not have any standard of care (SoC) treatment option or participant declines or is intolerant to be treated with SoC treatment.
- Subjects with advanced or metastatic solid tumors who have refused SoC; or for whom no reasonable SoC exists that would confer clinical benefit; or for whom standard therapy is intolerable, not effective, or not accessible.
- 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 least7 days (for Cohorts A, B, G and H), at least 2 months (for Cohort D), or at least 4 months (for Cohorts C, E and F) for females, and for at least 3 days for males [corresponding to the time needed to eliminate study intervention] after the last dose of study intervention.
- [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 days after last dose of study treatment.
- In Spain and United Kingdom: Only cohorts G and H will be open to enrollment.
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).
- Subjects who experienced Grade 3 or higher immune-related toxicity from prior immuno-oncology 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 within the previous 6 months, including 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.
- Parenteral antibiotics within 14 days of the first dose of study drug.
- History of allogenic or solid organ transplant.
- Uncontrolled diabetes mellitus or other uncontrolled immune-related endocrinopathies in the opinion of the Investigator.
- Known human immunodeficiency virus (HIV) infection or active infection with hepatitis C.
- For known uncontrolled hepatitis B virus (HBV) infection:
- i. Anti-HBV therapy started before initiation of IMP and HBV viral load <2000 IU/mL (104 copies/mL) are eligible. The anti-HBV therapy should continue throughout the treatment period. ii. Positive anti-HBc, positive anti HBs, negative HBsAg, and HBV virus load without HBV therapy are eligible.
- Received a live-virus vaccination ≤14 days prior to first dose of study drug. Seasonal flu and other inactivated vaccines that do not contain live virus are permitted.
- 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) > 450 milliseconds (msec) in males or > 470 msec in females.
- Known hypersensitivity or contraindications to any components of THOR-707, PEG, pegylated drugs, and E. coli derived-protein, checkpoint inhibitor, or anti-EGFR antibody 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 4 months after the last dose of study intervention for females and for at least 3 days for males 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 approval.
- For Cohort D only: patients with symptomatic keratitis and/or symptomatic dry eye should be excluded from enrollment. Patients who wear contact lenses should be advised to avoid contact lenses use as it could result in keratitis.
- Subjects with baseline oxygen saturation <92% are not eligible for enrollment.
- For participants in Cohort H: Participants with uveal or ocular or desmoplastic metastatic melanoma.
- The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Barcelona
Barcelona, Spain, 08023
Investigator
Tatiana Hernandez Guerrero
Status
Recruitment Complete
Condition(s) Treated at Site
Solid Tumor