SUPPORT HOTLINE (888) 901-2226
Donate Now

BRIEF TITLE: Study of SKB264 in Patients With Locally Advanced Unresectable /Metastatic Solid Tumors Who Are Refractory to Available Standard Therapies

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


  • Org Study ID: KL264-01
  • Secondary ID:
  • NCT ID: NCT04152499
  • NCT Alias:
  • Sponsor: Klus Pharma Inc. - Industry
  • Source: Klus Pharma Inc.

Brief 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)

Detailed Description


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).

Overal Status Start Date Phase Study Type
Recruiting February 28, 2020 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Phase I: Maximum Tolerated Dose (MTD)

Primary Outcome 1 - Time Frame: A minimum of 28 days after first infusion of study drug

Primary Outcome 2 - Measure: Phase II: Objective Response Rate (ORR)

Primary Outcome 2 - Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Condition:

  • Ovarian Epithelial Cancer
  • Gastric Adenocarcinoma
  • Pancreas Adenocarcinoma
  • Triple Negative Breast Cancer
  • Bladder Cancer

Eligibility

Criteria:
Inclusion Criteria:

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:

i. 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.

4. Measurable or evaluable disease by CT/MRI during dose escalation.

5. Patients should have an unresectable locally advanced or metastatic solid tumor that
is refractory to all standard therapies.

6. Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL.

7. 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).

8. 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.

9. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

10. 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.

- 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.

- 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.

- 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:

i. 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.

4. Measurable disease by CT/MRI.

5. Patients should have an unresectable locally advanced or metastatic solid tumor that
is refractory to all standard therapies.

6. Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL.

7. 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).

8. 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.

9. ECOG Performance Status 0 or 1.

10. 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.

- 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.

- 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.

- 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.

Exclusion Criteria:

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
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Jordi Rodon Ahnert, MD, PhD

Role: Study Chair

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: Study Manager

Phone: 650-237-9339

Email: jenny.li@kluspharma.com

Locations

Facility Status Contact
University of California Los Angeles
Los Angeles, California 90404
United States
Recruiting Zev Wainberg

Georgetown University
Washington, District of Columbia 20057
United States
Recruiting Paula Pohlmann

Florida Cancer Specialists and Research Institute
Sarasota, Florida 34232
United States
Recruiting Judy Wang

Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
United States
Recruiting Andrea Bullock

START MidWest
Grand Rapids, Michigan 49546
United States
Recruiting Manish Sharma

The University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Recruiting Susanna Ulahannan

Providence Cancer Institute, Franz Clinic
Portland, Oregon 97213
United States
Recruiting Rachel Sanborn

Mary Crowley Cancer Research
Dallas, Texas 75230
United States
Recruiting Minal Barve

MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting Jordie Rodon

Virginia Cancer Specialists
Fairfax, Virginia 22031
United States
Recruiting Alexander Spira