Basket Study of Leronlimab (PRO 140) in Patients With CCR5+ Locally Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT04504942
• Recruitment Status: Active, not recruiting
• First Posted: August 7, 2020
• Last Update Posted: July 1, 2022
• Sponsor: CytoDyn, Inc.
• Collaborator: Amarex Clinical Research
• Information provided by (Responsible Party): CytoDyn, Inc.

Tracking Information

• First Submitted Date: June 10, 2020
• First Posted Date: August 7, 2020
• Last Update Posted Date: July 1, 2022
• Actual Study Start Date: May 1, 2020
• Actual Primary Completion Date: November 7, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 5, 2020)

• Number, frequency, and severity of adverse events (AEs) [ Time Frame: From the time of first treatment until 12 weeks after study treatment completion ]
  Note: Adverse events will follow National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• Incidence of abnormal laboratory tests results [ Time Frame: Up to 12 weeks after study treatment completion ]
• Changes in Eastern Cooperative Oncology Group (ECOG) performance status from baseline to subsequent scheduled visits [ Time Frame: Up to 12 weeks after study treatment completion ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 5, 2020)

• Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first. [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment. ]
  Note: All patients who receive at least one dose of leronlimab will be included in the primary analyses of PFS. The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria will be used for objective tumor response assessment (when disease is measurable and non- measurable);
• Overall response rate (ORR, defined as CR + PR) in subjects with CCR5+ locally advanced or metastatic solid tumors treated with leronlimab [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment. ]
  Note: Overall response rate is defined as the proportion of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who achieve an overall response of complete response or partial response or stable disease in the total number of evaluable patients, assessed by RECIST v1.1.
• Clinical Benefit Rate (CBR, defined as CR + PR + SD) in subjects with CCR5+ locally advanced or metastatic solid tumors treated with leronlimab [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment. ]
  Note: Overall response rate is defined as the proportion of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who achieve an overall response of complete response or partial response or stable disease in the total number of evaluable patients, assessed by RECIST v1.1.
• Time to new metastases (TTNM) [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. ]
  Note: Recorded time from baseline metastatic disease (at time of enrollment) to the time of development of new metastasis in different site, assessed up to 6 months. New metastases in same site will be also recorded.
• The change from baseline in circulating tumor cells (CTC) level in the peripheral blood. [ Time Frame: From date of first treatment until the date of first documented progression or date of death from any cause, whichever came first. ]
  Note: Reported unit of measure will be the number of CTCs/milliliter. CTCs enumeration will be performed at baseline and at the time of response assessment, assessed up to 6 months. Fraction of baseline positive and change from ≥5 CTCs will be recorded and reported
• Overall survival defined as time in months from the date of first study treatment to the date of death [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment. ]
  Note: Patients will be followed from the start of treatment until 2 years post-treatment or death, whichever occurs first, and average survival time will be measured.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Basket Study of Leronlimab (PRO 140) in Patients With CCR5+ Locally Advanced or Metastatic Solid Tumors
• Official Title: Basket Study of Leronlimab (PRO 140) in Patients With CCR5+ Locally Advanced or Metastatic Solid Tumors

Brief Summary

This is a single arm phase II study with 30 patients of leronlimab (PRO 140) in patients with CCR5+ locally advanced or metastatic solid tumors.

Leronlimab (PRO 140) will be administered subcutaneously as weekly dose of 525 mg until disease progression or intolerable toxicity. Subjects participating in this study will be allowed to receive/continue standard-of-care chemotherapy or radotherapy as per the dosing schedule included on the package insert.

In this study, patients will be evaluated for tumor response approximately every 3 months or according to institution's standard practice by CT, PET/CT or MRI with contrast (per treating investigator's discretion) using the same method as at baseline.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor, Adult

Intervention

Drug: Leronlimab

Drug: Leronlimab 525mg

Study Arms

Experimental: Leronlimab 525mg

Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

Intervention: Drug: Leronlimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: August 5, 2020): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 15, 2022
• Actual Primary Completion Date: November 7, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Must have a histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors:

   1. who have disease progression on standard therapy,
   2. who are receiving a standard anticancer treatment but no subsequent approved treatment would be available upon progression,
   3. who are unable to receive standard therapy, or
   4. for whom standard therapy does not exist.

2. Demonstrate CCR5 + by IHC (>10% of primary or metastatic tumor cells shows membranous staining and/or high predominance of CCR5+ tumor-infiltrating leukocytes completed at the reference laboratory of Dr. Hallgeir Rui at Medical College of Wisconsin).

   Note: This test will be done as part of the pre-screening period. It will be performed in archival metastatic tissue. If archival tissue is not available then, fresh biopsy will be done;

3. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (in case archival tissue is not available);
4. Patients must have measurable disease based on RECIST v1.1;
5. ≥ 18 years of age;
6. Patients must exhibit a/an ECOG performance status of 0-1;
7. Life expectancy of at least 6 months;

8. Patients must have adequate organ and bone marrow function within 28 days prior to registration, as defined below:

   • leukocytes ≥ 3,000/mcL;
   • absolute neutrophil count ≥ 1,500/mcL;
   • platelets ≥ 100,000/mcL;
   • total bilirubin: within normal institutional limits;
   • AST(SGOT) and ALT(SPGT) ≤ 2.5 X institutional upper limit of normal (ULN) (applicable to all patients, irrespective of liver disease or metastasis); and
   • creatinine: within normal institutional limits.
9. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.

10. Females of child-bearing potential (FOCBP) and males must agree to use two medically accepted methods of contraception with hormonal or barrier method of birth control, or abstinence, prior to study entry, for the duration of study participation and for 60 days after the last dose of study drug (Refer to Appendix 1). Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    • Has not undergone a hysterectomy or bilateral oophorectomy; and
    • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months).
11. FOCBP must have a negative serum pregnancy test at Screening Visit and negative urine pregnancy test prior to receiving the first dose of study drug; and
12. Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.

Exclusion Criteria:

1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days prior to enrollment;
2. Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible;
3. Patients who have had prior exposure to CCR5 antagonists are not eligible;
4. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability;
5. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator;
6. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial; and
7. Is pregnant or breastfeeding, or expecting to conceive or have children within the projected duration of the trial, starting with the pre-screening or screening visit through the duration of study participation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04504942
• Other Study ID Numbers: CD09_Basket
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: CytoDyn, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: CytoDyn, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Amarex Clinical Research
• Investigators: Not Provided
• PRS Account: CytoDyn, Inc.
• Verification Date: September 2021