Phase I-II, FIH, TROP2 ADC, Advanced Unresectable/Metastatic Solid Tumors, Refractory to Standard Therapies (A264)
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ClinicalTrials.gov Identifier: NCT04152499 |
Recruitment Status :
Recruiting
First Posted : November 5, 2019
Last Update Posted : August 18, 2020
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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)
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Ovarian Epithelial Cancer Gastric Adenocarcinoma Pancreas Adenocarcinoma Triple Negative Breast Cancer Bladder Cancer | Drug: SKB264 | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 78 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | February 28, 2020 |
Estimated Primary Completion Date : | December 2021 |
Estimated Study Completion Date : | December 2022 |

Arm | Intervention/treatment |
---|---|
Experimental: Phase I: Dose Escalation
Five dose levels have been selected for evaluation in the Phase I part of the study: 2, 4, 6, 9, and 12 mg/kg of SKB264
|
Drug: SKB264
SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells. |
Experimental: Phase II: • Cohort 1
Histologically documented, incurable, locally advanced or metastatic Gastric Adenocarcinoma refractory to standard therapies.
|
Drug: SKB264
SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells. |
Experimental: Phase II: • Cohort 2
Histologically documented, incurable, locally advanced or metastatic Pancreatic Adenocarcinoma refractory to standard therapies.
|
Drug: SKB264
SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells. |
Experimental: Phase II: • Cohort 3
Histologically documented, incurable, locally advanced or metastatic Bladder Cancer refractory to standard therapies.
|
Drug: SKB264
SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells. |
- Phase I: Maximum Tolerated Dose (MTD) [ Time Frame: A minimum of 28 days after first infusion of study drug ]Number of patients with dose limiting toxicities
- Phase II: Objective Response Rate (ORR) [ 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 ]As determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which will be complete response (CR) + partial response (PR)
- Phase I: Dose Limiting Toxicities (DLTs) [ Time Frame: A minimum of 28 days after first infusion of study drug ]DLT Reporting at D28
- Phase I:Treatment-related adverse events as assessed by CTCAE v5 [ Time Frame: Every 2 weeks from date of enrollment until until 30 days after last infusion of study drug or the end of treatment visit, whichever occurs later ]Treatment-related adverse event reporting
- Phase I:Objective Response Rate (ORR) [ 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 ]As determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which will be complete response (CR) + partial response (PR)
- Phase I and II: Duration of response (DOR) [ Time Frame: Minimum of 28 days 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 ]DOR in patients who responded during time frame per protocol
- Phase I and II: Progression Free Survival (PFS) [ 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 ]Kaplan Meier Curve for survival without progression in patients who responded to treatment
- Phase I and II: Overall Survival (OS) [ 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 ]Kaplan Meier Curve for survival in all enrolled patients
- Phase I and II: Anti-drug antibodies (ADA) [ Time Frame: Minimum of 28 days 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 ]ADA data from Bioanalytical Lab.
- Phase I and II: Maximum observed serum or plasma concentration (Cmax) [ Time Frame: Through study completion, an average of 24 months ]One of the PK (pharmacokinetics) parameters for SKB264
- Phase I and II: Area under the serum or plasma concentration time curve from 0 to infinity (AUC[0-∞]) [ Time Frame: Through study completion, an average of 24 months ]One of the PK (pharmacokinetics) parameters for SKB264
- Phase I and II: Clearance (CL) [ Time Frame: Through study completion, an average of 24 months ]One of the PK (pharmacokinetics) parameters for SKB264
- Phase I and II: Terminal phase elimination half life (t½) [ Time Frame: Through study completion, an average of 24 months ]One of the PK (pharmacokinetics) parameters for SKB264
- Phase I and II: Volume of distribution at terminal phase (Vz) [ Time Frame: Through study completion, an average of 24 months ]One of the PK (pharmacokinetics) parameters for SKB264
- Phase I and II: Volume of distribution at steady state (Vss) [ Time Frame: Through study completion, an average of 24 months ]One of the PK (pharmacokinetics) parameters for SKB264
- Phase I and II: Levels of TROP2 (trophoblast antigen 2) expression in tumor tissue [ Time Frame: Through study completion, an average of 24 months ]To investigate any potential correlations of TROP2 (trophoblast antigen 2) levels with responses and toxicity

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Phase I:
- Patients must be able to provide documented voluntary informed consent.
- Male or female patient ≥ 18 years.
-
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.
- Measurable or evaluable disease by CT/MRI during dose escalation.
- Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to all standard therapies.
- Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL.
- 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).
- 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.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
-
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.
- 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:
- Patients must be able to provide documented voluntary informed consent.
- Male or female patient ≥ 18 years.
-
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.
- Measurable disease by CT/MRI.
- Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to all standard therapies.
- Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL.
- 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).
- 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.
- ECOG Performance Status 0 or 1.
-
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.
- 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:
- 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).
- Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
- Require supplemental oxygen for daily activities.
- Documented Grade ≥ 2 peripheral neuropathy.
- 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.
- 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.
- Any experimental therapy within 4 weeks or five half-lives, whichever is shorter, of first infusion of study drug.
- Any major surgical procedure within 4 weeks of first infusion of study drug.
- 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.
- Have known prior positive test results for human immunodeficiency virus.
- Uncontrolled hypertension or diabetes.
- 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.
- Pregnancy or lactation.
- Left ventricular ejection fraction < 45% determined by echocardiogram or multiple gated acquisition scan.
- Resting QTc (corrected QT interval) > 480 msec at baseline.
- Ascites requiring paracentesis ≥1 per week.
- Symptomatic pleural effusion.
- New thromboembolic events over the last 6 months
Phase II:
- Any patient who was treated in the Phase I part of this study.
- 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).
- Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
- Require supplemental oxygen for daily activities.
- Documented Grade ≥ 2 peripheral neuropathy.
- 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.
- Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
- Any experimental therapy within 4 weeks or 5 half-lives, whichever is shorter of first infusion of study drug.
- Any major surgical procedure within 4 weeks of first infusion of study drug.
- 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.
- Have known prior positive test results for human immunodeficiency virus.
- Uncontrolled hypertension or diabetes.
- 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.
- Pregnancy or lactation.
- Left ventricular ejection fraction < 45% determined by echocardiogram or multiple gated acquisition scan.
- Resting QTc (corrected QT interval) > 480 msec at baseline.
- Ascites requiring paracentesis ≥1 per week.
- Symptomatic pleural effusion.
- New thromboembolic events over the last 6 months

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04152499
Contact: Study Manager | 650-237-9339 | jenny.li@kluspharma.com |
United States, California | |
University of California Los Angeles | Recruiting |
Los Angeles, California, United States, 90404 | |
Contact: Zev Wainberg | |
United States, District of Columbia | |
Georgetown University | Recruiting |
Washington, District of Columbia, United States, 20057 | |
Contact: Paula Pohlmann | |
United States, Florida | |
Florida Cancer Specialists and Research Institute | Recruiting |
Sarasota, Florida, United States, 34232 | |
Contact: Judy Wang | |
United States, Massachusetts | |
Beth Israel Deaconess Medical Center | Recruiting |
Boston, Massachusetts, United States, 02215 | |
Contact: Andrea Bullock | |
United States, Michigan | |
START MidWest | Recruiting |
Grand Rapids, Michigan, United States, 49546 | |
Contact: Manish Sharma | |
United States, Oklahoma | |
The University of Oklahoma Health Sciences Center | Recruiting |
Oklahoma City, Oklahoma, United States, 73104 | |
Contact: Susanna Ulahannan | |
United States, Oregon | |
Providence Cancer Institute, Franz Clinic | Recruiting |
Portland, Oregon, United States, 97213 | |
Contact: Rachel Sanborn | |
United States, Texas | |
Mary Crowley Cancer Research | Recruiting |
Dallas, Texas, United States, 75230 | |
Contact: Minal Barve | |
MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Jordie Rodon | |
United States, Virginia | |
Virginia Cancer Specialists | Recruiting |
Fairfax, Virginia, United States, 22031 | |
Contact: Alexander Spira | |
China | |
Shanghai East Hospital | Recruiting |
Shanghai, China | |
Contact: Jin Li, MD | |
Principal Investigator: Jin Li, MD |
Study Chair: | Jordi Rodon Ahnert, MD, PhD | M.D. Anderson Cancer Center |
Responsible Party: | Klus Pharma Inc. |
ClinicalTrials.gov Identifier: | NCT04152499 |
Other Study ID Numbers: |
KL264-01 |
First Posted: | November 5, 2019 Key Record Dates |
Last Update Posted: | August 18, 2020 |
Last Verified: | August 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
TROP2, ADC |
Adenocarcinoma Triple Negative Breast Neoplasms Carcinoma, Ovarian Epithelial Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Urogenital Neoplasms Neoplasms by Site Breast Neoplasms |
Breast Diseases Skin Diseases Ovarian Neoplasms Endocrine Gland Neoplasms Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Endocrine System Diseases Gonadal Disorders |