Solid Tumor, Adult
Conditions
Brief summary
A single arm phase II study with 30 patients of leronlimab (PRO 140) in patients with CCR5+ locally advanced or metastatic solid tumors.
Detailed description
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 radiotherapy 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.
Interventions
DRUGLeronlimab
Drug: Leronlimab 525mg
Sponsors
CytoDyn, Inc.
Amarex Clinical Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs). | From the time of first treatment (T1) until the last study visits completion (up to approximately 16 months) | Adverse events were elicited through direct questioning and subject reports. Any abnormalities in visit evaluations, physical examination findings or laboratory results that the investigator believed were clinically significant to the research subject were reported as adverse events. |
| Changes in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Subsequent Scheduled Visits | From the time of first treatment (T1) until the last study visits completion (up to approximately 16 months) | The ECOG was utilized to assess the ability of patients to tolerate treatment. The ECOG is a 5-point scale, where a higher score indicates a greater lack of tolerance of the treatment. Response choices included: 0 = Asymptomatic; Fully active, able to carry on all pre-disease performance without restriction, 1 = Symptomatic but completely ambulatory; Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 2 = Symptomatic, \<50% in bed during the day; Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours, 3 = Symptomatic, \>50% in bed during the day; Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours, 4 = Bedbound; Completely disabled; cannot carry on any selfcare; totally confined to bed or chair, 5 = Dead. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. Participants were followed on study until last study visit completion up to approximately 16 months. | The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria was used for objective tumor response assessment (when disease is measurable and non- measurable); PFS is calculated from the date of first dose of leronlimab until date of clinical progressions. |
| Overall Response Rate (ORR, Defined as CR (Complete Response) + PR (Partial Response)) in Subjects With CCR5+ Locally Advanced or Metastatic Solid Tumors Treated With Leronlimab. | 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. Participants were followed on study until last study visit completion up to approximately 16 months. | Overall response rate is defined as the percentage 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. |
| Mean Time to New Metastases (TTNM) | From the time of first treatment (T1) until the last study visits completion (up to approximately 16 months). | Recorded time from baseline metastatic disease (at time of enrollment) to the time of development of new metastasis in different site. New metastases in same site will be also recorded. TTNM will be calculated according to the formula: TTNM=(Date of new metastases - Date of first treatment) + 1. |
| The Change From Baseline in Circulating Tumor Cells (CTC) Level in the Peripheral Blood. | From date of first treatment until the date of first documented progression or date of death from any cause, whichever came first. From the time of first treatment (T1) until the last study visits completion (up to approximately 16 months). | Reported unit of measure will be the number of CTCs/milliliters. CTCs enumeration will be performed at baseline and at the time of response assessment. 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 | Overall survival is calculated by long-term follow-up date - PRO 140 (leronlimab) start date, up to approximately 57 months. | Overall survival defined as time in months from the date of first study treatment to the date of death. Patients will be followed from the start of treatment (first dose) until long-term follow up date (up to 2 years post-treatment or death), whichever occurs first, and average survival time will be measured. |
Countries
United States
Contacts
STUDY_DIRECTORJacob Lalezari, MD
CytoDyn, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 54.87 years STANDARD_DEVIATION 15.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 16 |
| other Total, other adverse events | 11 / 16 |
| serious Total, serious adverse events | 3 / 16 |
Outcome results
None listed