MC# 21-46 - A Phase I, Open-Label, Dose Escalation and Expansion Study of TH1902 in Patients with Advanced Solid Tumors

  • Agent(s): TH1902
  • Disease Type(s): Breast, Endometrial, Melanoma, Ovarian, Prostate, Thyroid, Lung-SCLC, Breast- Triple Negative
  • Phase(s): I
  • Drug Classification(s): Cytotoxic Therapy, Targeted Therapy
  • Molecular Target(s): SORT1

Mechanism of Action

TH1902 is docetaxel with a targeting peptide that interacts with Sortilin, a membrane protein overexpressed by many tumors.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much of TH-1902 can be given with an acceptable level of side effects
  • The effects of TH-1902 (good and bad)
  • How much of TH-1902 is absorbed into the blood and how fast it is removed
  • If research tests can be used in the future to predict who will benefit from TH-1902
Inclusion Criteria

Patients must meet all the following inclusion criteria within 21 days of study participation (Cycle 1, Day 1) in order to be eligible to participate in the study:

  1. Are ≥18 years old males or females
  2. Are capable of understanding and have voluntarily signed the informed consent document and willing to comply with study requirements
  3. Have histologically or cytologically confirmed diagnostic of metastatic cancer or advanced-stage solid tumor that has progressed following standard therapy or for which, in the opinion of the Investigator, no standard effective therapy is available or the patient has a contraindication to or declines standard therapy
  4. Have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
  5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  6. Have an expected survival of at least 3 months
  7. Have a negative pregnancy test result at screening confirmed by a serum beta-human chorionic gonadotropin (β-HCG) (for women of childbearing potential (WOCBP); not applicable to patients who are unable to become pregnant, including those with bilateral oophorectomy, salpingectomy and/or hysterectomy or postmenopausal [no menses for the previous 12 months]) or those that have had definitive radiation therapy to the pelvis.  The test must be performed within 1 week before Day 1 of treatment.
  8. WOCBP who are sexually active with a nonsterilised male partner (sterilised males should be ≥1 year postvasectomy and have confirmed that they have obtained documentation of the absence of sperm in the ejaculate) and male patients whose sexual partners are WOCBP should agree to remain abstinent (refrain from heterosexual intercourse) or use 2 effective methods of contraception, including at least 1 method with a failure rate of <1% per year, during the treatment period and for at least 6 months and 3 months for female and male patients, respectively, following the last dose of TH1902.
    • Effective contraceptive measures include the following:
      • Intrauterine device (e.g. IUD) plus one barrier method
      • Oral, implantable or injectable contraceptive plus one barrier method
      • Two barrier methods. Effective barrier methods are male or female condoms, diaphragms and spermicides (cream or gel that contains a chemical to kill sperm)
  9. WOCBP must agree to not donate ova and agree to ongoing pregnancy testing during the course of the study and 6 months following the last dose of TH1902.  Male patients must refrain from donating sperm during the course of the study and 3 months following the last dose of TH1902.
  10. Male patients with pregnant female partners, must agree to remain abstinent or use a condom (latex condom is recommended) during the treatment period and for at least 3 months after the last dose of TH1902 to avoid exposing the embryo, even if he has undergone a successful vasectomy.
  11. Patients with HIV/HBV/HBC will not be excluded from entry into the study provided the following criteria are met:
    • Patients with HIV infection must have CD4+ T-cell (CD4+) counts ≥ 350 cells/µL
    • The following eligibility criteria are for patients with evidence of chronic HBV infection or patients with history of chronic HCV or who are virologically suppressed on HCV treatment
      • Liver-related laboratory eligibility criteria should be the same as that for the general population
      • Exceptions: AST/ALT and bilirubin criteria may be less stringent in patients with cancers such as hepatocellular carcinoma and cholangiocarcinoma in whom hepatic function based on Child-Pugh score should be used
      • Patients with chronic HBV infection with active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy
      • Patients on concurrent HCV treatments must have HCV below the limit of quantification
      • Patients with untreated HCV may be enrolled if the HCV is stable, the patient is not at risk for hepatic decompensation, and the investigational cancer treatment is not expected to exacerbate the HCV infection
    • Patients with chronic HBV infection with active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy
    • Patients with a history of HCV infection should have completed curative antiviral treatment and HCV viral load must be below the limit of quantification.  For incurable cancers, patients with untreated HCV may be enrolled if the HCV is stable, the patient is not at risk for hepatic decompensation, and the investigational cancer treatment is not expected to exacerbate the HCV infection.

Patients must meet the following additional criterion to enter in Part 2:

  1. Histologically or cytologically confirmed TNBC, gynecological cancer (epithelial ovarian or endometrial cancer), colorectal cancer, or pancreatic cancer, and for which no standard effective therapy is available
Exclusion Criteria

Patients who meet any one of the following criteria at baseline will be excluded from study participation:

  1. Have received chemotherapy, biologic therapy, immunotherapy, radiotherapy (except palliative radiation delivered to <20% of bone marrow), or investigational agents within 4 weeks before the first dose of study drug.  Patients who have received targeted therapy (investigational or approved) will not have received their last dose within 4 weeks, or within 5 half-lives (whichever is shorter).
  2. Have known hypersensitivity to docetaxel or to any excipients in the TH1902 investigational medicinal product (IMP) (e.g. polysorbate 80, predominantly known as Tween® 80)
  3. Have severe toxicity with previous taxane treatment
  4. Any past or current history of brain, leptomeningeal or spinal metastases
  5. Are pregnant or breastfeeding
  6. Had any acute viral (including COVID-19), bacterial, or fungal infection that requires parenteral therapy within 14 days prior to study treatment (Cycle 1, Day 1)
  7. Have received a live vaccine within 30 days prior to administration of the IMP
  8. Had treatment with cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C8 (CYP2C8) enzyme-inducing or enzyme inhibiting drugs within 14 days prior to treatment with the IP (Cycle 1 Day 1) (Refer to Appendix 3)
  9. Have any of the following hematologic abnormalities at baseline:
    • Hemoglobin <9.0 g/dL (90 g/L)*
    • ANC <1.5 x 109/L (1500/mm3)
    • Platelet count <100 x 109/L (100,000/mm3) *Patients may be transfused with packed red blood cells prior to TH1902 infusion, if clinically warranted.  A post-transfusion hemoglobin assessment may qualify the patient for participation.
  10. Have any of the following serum chemistry abnormalities at baseline:
    • Bilirubin >ULN
    • ALK Phos >2.5 with an aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >1.5 times the ULRR, or >5 times ULRR for patients with documented liver metastases
    • Serum calcium above ULRR
    • Creatinine clearance (calculated according to the Cockcroft & Gault formula (Cockcroft, 1976)) < 60 mL/ min):
      • Female CrCl = (140 - age in years) × weight in kg × 0.85 / (serum creatinine in mg/dL x 72)
      • Male CrCL = (140 - age in years) × weight in kg × 1.00 / (serum creatinine in mg/dL x 72)
  11. Baseline corrected interval between Q and T waves on electrocardiogram (ECG) (QTc) ≥ 470 msec using Fridericia's formula
  12. Have unstable or uncompensated respiratory, cardiac, hepatic or renal disease or any other organ system dysfunction, medical condition, or laboratory abnormality which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with the evaluation of the IMP
  13. Have evidence of persistent grade 2 or greater neurotoxicity

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT04706962

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Re: MC# 21-46