Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

Summary

A Phase I-II, First-in-Human Study of SKB264 in Patients with Locally Advanced Unresectable/Metastatic Solid Tumors who are refractory to Available Standard Therapies. Patient must have historically documented, incurable, locally advanced or metastatic cancer that are refractory to standard therapies of one of the following types: i. Ovarian epithelial cancer (Phase I only) ii. Gastric adenocarcinoma (Phase I-II) iii. Pancreatic adenocarcinoma (Phase I-II) iv. Triple negative breast cancer (Phase I only) v. Bladder cancer (Phase I-II)

Official Title

A Phase I-II, First-in-Human Study of SKB264 in Patients With Locally Advanced Unresectable /Metastatic Solid Tumors Who Are Refractory to Available Standard Therapies

Details

This is an open label, Phase I-II, first in human (FIH) study for SKB264 as monotherapy in patients who have locally advanced unresectable or metastatic solid tumor that is refractory to all standard therapies. TROP2 (trophoblast antigen 2) assessments will not be performed prior to enrollment but it will be assessed retrospectively. Confirmation of TROP2 (trophoblast antigen 2) expression by immunohistology or other means is not required, but the Sponsor will request fresh tumor biopsy or tissue specimens from archived materials for determination of TROP2 (trophoblast antigen 2) expression retrospectively. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy whose tumor is refractory to standard therapies. Patients will receive study drug as a single IV infusion at the prescribed dose level at each administration. Cycles will continue until disease progression or unacceptable toxicity. The study is divided into 2 parts (Phase I and Phase II).

Keywords

Ovarian Epithelial Cancer Gastric Adenocarcinoma Pancreas Adenocarcinoma Triple Negative Breast Cancer Bladder Cancer TROP2, ADC Adenocarcinoma Triple Negative Breast Neoplasms Carcinoma, Ovarian Epithelial SKB264

Eligibility

You can join if…

Open to people ages 18 years and up

Phase I:

  1. Patients must be able to provide documented voluntary informed consent.
  2. Male or female patient ≥ 18 years.
  3. Histologically documented, incurable, locally advanced or metastatic cancer that are refractory to standard therapies of one of the following types:
  4. Ovarian epithelial cancer ii. Gastric adenocarcinoma iii. Pancreatic adenocarcinoma iv. Triple negative breast cancer v. Bladder cancer

Note: Confirmation of TROP2 expression by immunohistology or other means is not required, but the Sponsor will request tissue specimens from archived materials or fresh tumor biopsy for determination of TROP2 expression retrospectively.

  1. Measurable or evaluable disease by CT/MRI during dose escalation.
  2. Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to all standard therapies.
  3. Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL.
  4. Serum bilirubin ≤ 1.5 mg/dL (Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ×ULN may be enrolled)., aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
  5. Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration, or Modification of Diet in Renal Disease formulas. Note that 24 hour urine collection is not required but is allowed.
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
  7. . For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception during study treatment that results in a low failure rate of <1% per year when used consistently and correctly. Female and male patient treated with SKB264 should continue contraception use for 7 months after the last dose. Such methods include combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
  8. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drug. The same rules are valid for male patients involved in this clinical trial if they have a partner of childbirth potential. Male patients must always use a condom.
  9. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
  10. Women are excluded from birth control if they had had tubal ligation or a hysterectomy.
  11. . Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.

Phase II:

  1. Patients must be able to provide documented voluntary informed consent.
  2. Male or female patient ≥ 18 years.
  3. Histologically documented, incurable, locally advanced or metastatic cancer refractory to standard therapies as follows:
  4. Cohort 1: Gastric adenocarcinoma ii. Cohort 2: Pancreatic adenocarcinoma iii.

Cohort 3: Bladder cancer

Note: Confirmation of TROP2 expression by immunohistology or other means is not required, but the Sponsor will request tissue specimens from archived materials or fresh tumor biopsy for determination of TROP2 expression retrospectively.

  1. Measurable disease by CT/MRI.
  2. Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to all standard therapies.
  3. Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL.
  4. Serum bilirubin ≤ 1.5 mg/dL (Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ×ULN may be enrolled)., aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
  5. Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 24 hour urine collection is not required but is allowed.
  6. ECOG Performance Status 0 or 1.
  7. . For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception during study treatment that results in a low failure rate of <1% per year when used consistently and correctly. Female and male patient treated with SKB264 should continue contraception use for 7 months after the last dose. Such methods include combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
  8. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drug. The same rules are valid for male patients involved in this clinical trial if they have a partner of childbirth potential. Male patients must always use a condom.
  9. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
  10. Women are excluded from birth control if they had had tubal ligation or a hysterectomy.
  11. . Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.

You CAN'T join if...

Phase I:

  1. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
  2. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
  3. Require supplemental oxygen for daily activities.
  4. Documented Grade ≥ 2 peripheral neuropathy.
  5. Documented moderate to severe dry eye syndrome, moderate to severe Meibomian gland disease and/or blepharitis, keratoconjunctivitis sicca (KSC), history of corneal ulcers and/or corneal pathology that would predispose the subjects to worsening dry eye and/or the inability to heal the cornea, keratoconjunctivitis and/or corneal ulcer established by targeted ophthalmologic exam and not responsive to ophthalmic management recommended in this protocol during screening period.
  6. Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks or five half-lives, whichever is shorter, of first infusion of study drug.
  7. Any experimental therapy within 4 weeks or five half-lives, whichever is shorter, of first infusion of study drug.
  8. Any major surgical procedure within 4 weeks of first infusion of study drug.
  9. Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis. Patients who have positive hepatitis B virus test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti hepatitis B core protein, and positive antibody to the HBsAg (anti-HBs) are not excluded.
  10. . Have known prior positive test results for human immunodeficiency virus.
  11. . Uncontrolled hypertension or diabetes.
  12. . Subjects who require use of strong inhibitors or inducers of CYP3A4 at least 14 days prior to and throughout Study. Use of strong inhibitors or inducers of CYP3A4 is not allowed in this study. List of representative examples of strong inhibitors or inducers of CYP3A4 is provided in Appendix III.
  13. . Pregnancy or lactation.
  14. . Left ventricular ejection fraction < 45% determined by echocardiogram or multiple gated acquisition scan.
  15. . Resting QTc (corrected QT interval) > 480 msec at baseline.
  16. . Ascites requiring paracentesis ≥1 per week.
  17. . Symptomatic pleural effusion.
  18. . New thromboembolic events over the last 6 months

Phase II:

  1. Any patient who was treated in the Phase I part of this study.
  2. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
  3. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
  4. Require supplemental oxygen for daily activities.
  5. Documented Grade ≥ 2 peripheral neuropathy.
  6. Documented moderate to severe dry eye syndrome, moderate to severe Meibomian gland disease and/or blepharitis, keratoconjunctivitis sicca (KSC), history of corneal ulcers and/or corneal pathology that would predispose the subjects to worsening dry eye and/or the inability to heal the cornea, keratoconjunctivitis and/or corneal ulcer established by targeted ophthalmologic exam and not responsive to ophthalmic management recommended in this protocol during screening period.
  7. Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
  8. Any experimental therapy within 4 weeks or 5 half-lives, whichever is shorter of first infusion of study drug.
  9. Any major surgical procedure within 4 weeks of first infusion of study drug.
  10. . Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis. Patients who have positive hepatitis B virus test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti hepatitis B core protein, and positive antibody to the HBsAg (anti-HBs) are not excluded.
  11. . Have known prior positive test results for human immunodeficiency virus.
  12. . Uncontrolled hypertension or diabetes.
  13. . Subjects who require use of strong inhibitors or inducers of CYP3A4 at least 14 days prior to and throughout Study. Use of strong inhibitors or inducers of CYP3A4 is not allowed in this Study. List of representative examples strong inhibitors or inducers of CYP3A4 is provided in Appendix III.
  14. . Pregnancy or lactation.
  15. . Left ventricular ejection fraction < 45% determined by echocardiogram or multiple gated acquisition scan.
  16. . Resting QTc (corrected QT interval) > 480 msec at baseline.
  17. . Ascites requiring paracentesis ≥1 per week.
  18. . Symptomatic pleural effusion.
  19. . New thromboembolic events over the last 6 months

Locations

  • University of California Los Angeles accepting new patients
    Los Angeles California 90404 United States
  • Providence Cancer Institute, Franz Clinic accepting new patients
    Portland Oregon 97213 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Klus Pharma Inc.
ID
NCT04152499
Phase
Phase 1/2
Study Type
Interventional
Last Updated