A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (THOR-707-101) (HAMMER)
Brief description of study
- Evaluate the safety and tolerability of THOR-707 as a single agent and as a combination therapy (identify Dose Limiting Toxcitiy (DLTs) in Cohort A, B, C, and D, Adverse Events (AEs)/serious adverse event (SAE) profile)
- Define the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of THOR-707 as a single agent and as a combination therapy (Cohort A, B, C, and D)
- Evaluate preliminary anti-tumor activity of THOR-707 as a single agent and as a combination therapy by determination of the objective response rate (ORR) defined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- Determine time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and disease control rate (DCR) of THOR-707 as a single agent and as a combination therapy
Detailed description of study
The study duration per participant is approximately 24 months (inclusive of follow-up).
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Metastasis
Age: 18 Years
Gender: Male or Female
Key Inclusion Criteria:
- Measurable disease per RECIST v1.1. For Cohorts E & F participants must have at least 2 measurable lesions, one of which is accessible to safely perform pre & on-treatment biopsy.
- 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. (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.
- 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 4 months after the last dose of study intervention for females and for at least 3 days after the last dose of study intervention for males.
- [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.
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 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.
- Known human immunodeficiency virus (HIV) infection or active infection with hepatitis C.
- Known uncontrolled hepatitis B virus (HBV) infection:
- 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
- Positive anti-HBc, positive anti HBs, negative HBsAg, and HBV virus load without HBV therapy are eligible
- 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 after the last dose of study intervention for males.
- 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.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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