Clinical trial NCT06854653: A Phase 2 Study of PTX 100 in Patients With Relapsed/Refractory CTCL
Official title: An Open-Label, Phase 2 Study of PTX-100 Monotherapy in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: CTCL
Keywords: Relapsed or refractory Cutaneous T Cell Lymphoma
CTCL
PTX-100
Mycosis Fungoides
Sezary Syndrome
T Cell Lymphoma
Non-Hodgkin Lymphoma
Cutaneous Lymphoma
Lead sponsor: Prescient Therapeutics, Ltd.
Sponsor class: INDUSTRY
First posted: 2025-03-03
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised parallel recruitment into 2 treatment arms, 500mg/m2 and 1000-mg/m2 for Phase 2a.

Phase 2b will be non-randomised and are single arm treatment group. The recommended optimal dose which was determined in Phase 2a will be used in Phase 2b.
Primary purpose: TREATMENT

Brief summary: This is an open-label, phase 2 randomized study to evaluate the efficacy, safety, pharmacokinetics (PK) and pharmadynamics (PD), of PTX-100 monotherapy at 500 or 1000 mg/m2 in patients with relapsed/refractory Cutaneous T-Cell Lymphoma (CTCL).

PTX-100 will be administered by IV infusion over 60 minutes on days 1 to 5 of a 14-day cycle for 4 cycles, then 21 day cycle thereafter. Subjects will be treated or followed up, if subjects discontinue treatment, for up to 18 months.

Detailed description: PTX-100 from a Phase I study shown to help some CTCL patients. This Phase II study will be conducted in a larger population size and there will be initially two groups/arms in the first phase called Phase 2a. This phase will randomize and enroll 20 subjects into the 500 mg/m2 and 20 subjects into the 1000 mg/m2 PTX treatment arms. After determining the recommended optimal dose from phase 2a, for Phase 2b, 75 subjects will then be allocated into this single arm part of the study.

Once subject has signed the informed consent, subject will undergo a 28 day screening period, where eligibility would be determined. Once subject is eligible, subject will be dosed with IP. Safety bloods will be taken on the first day of every cycle. Pharmacokinetics (PKs) which are blood samples sent to the Sponsors associated laboratory and will be analysed on how PTX-100 interacts biologically. PKs will be taken on Cycle1Day1(C1D1) to C1D5 and C1D8 for the first 4 cycles. Subject will also undergo skin evaluation and safety exams at every Cycle Day 1. Subjects will also complete quality of life questionnaires at every Cycle Day1. Subjects will be on the study for 18months, until disease progression, unacceptable toxicity, participant or Investigator decision, or until study treatment discontinuation criteria are met, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

1. Adult patient ≥18 years of age at the time of signing the informed consent.
2. Patient is capable of giving adequate signed informed consent
3. Have a confirmed diagnosis of CTCL with histological confirmation
4. Patients must have greater than or equal to Stage Ib disease.
5. Has received and failed (or intolerant of) at least 2 prior lines of prior systemic therapy for their disease.
6. Has measurable disease defined by at least one of the following, within 28 days prior to start of study treatment: by evaluable by mSWAT or quantifiable by flow cytometry or morphology in blood or measurable by Lugano Criteria.
7. On a stable dose of systemic corticosteroid (\< 10 mg prednisone or equivalent) are permitted. Participants on a stable dose of topical corticosteroids are permitted.
8. Washout period- must be 2 weeks (4 weeks for monoclonal antibodies) or 5 -half-lives (whichever is longer) since any prior anti-cancer therapy.
9. Must be human T-cell lymphotropic virus type 1 (HTLV1) negative.
10. Has an ECOG PS of 0 to 2.
11. Life expectancy of 3 months or greater
12. Has adequate bone marrow function.
13. Has adequate hepatic function.
14. Has adequate Renal function.
15. Has adequate coagulation function.
16. Patients with Human Immunodeficiency virus (HIV) must be on established and stable effective anti-retroviral therapy for at least 4 weeks and have an HIV viral load of less than 400 copies/mL.
17. Male patients are eligible to participate if they agree to use a highly effective contraception during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period.
18. Female patients are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies:

    -Not a woman of childbearing potential (WOCBP).
    * OR
    * A WOCBP who agrees to use a contraceptive method that is highly effective (with a failure rate of \< 1% per year) or be abstinent from heterosexual intercourse as their preferred method and usual lifestyle, beginning the time of informed consent, during the treatment period and for at least 3 months after the last dose of study treatment.
19. A WOCBP must have a negative serum pregnancy within 72 hours of the first dose of study treatment.
20. Must be willing and able to adhere to the study as judged by the Investigator.

Exclusion Criteria:

1. Patients with known central nervous system involvement.
2. Patients who require the use of strong inhibitors or inducers of CYP enzymes or transporters (e.g., CYP3A4, 2D6, 2C19) or (P-gp, BCRP, OATP1B1, OATP1B3, OAT1. OAT3, OCT2, MATE1 and MATE2-K). Patients who are receiving these medications at Screening can be enrolled into the trial if they discontinue them for at least 14 days or 5 half-lives, whichever is longer, before they commence PTX-100. An alternative pharmacological treatment should be instituted by the treating clinician based on clinical judgement.
3. Significant cardiovascular disease. A history of, or concurrent interstitial lung disease or severely impaired lung function.

5. Active viral, bacterial, fungal infection or other serious infection requiring ongoing systemic treatment. Routine antimicrobial prophylaxis is permitted.

6. Medical history of another malignant tumor within the past 5 years. Exceptions are patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ who have undergone curative therapy with no evidence of disease.

7. On an immunomodulatory drug for concomitant or intercurrent conditions or who have received any of these agents within 4 weeks of baseline.

8. Patients with active viral (any etiology) hepatitis are excluded. However, patients with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a positive hepatitis B surface antigen test and a positive anti-hepatitis core antigen antibody test) who have a viral load below the limit quantification (HBV deoxyribose nucleic acid titer \< 1000 cps/mL or 200 IU/mL) and are not currently on viral suppressive therapy may be eligible and should be discussed with the Medical Monitor. Patients with a history of hepatitis C virus infection who have completed curative antiviral treatment and have a viral load below the limit of quantification may be eligible and should be discussed with the Medical Monitor.

9. A history or current evidence of any condition, laboratory abnormality or other circumstance that might confound the results of the study or interfere with patient participation for the full duration of the study.

10. Prior allogeneic or autologous hematopoietic transplantation 11. Has a known psychiatric disorder that would interfere with compliance with the requirements of the study.

12. Is a consumer of illicit or recreational drugs or has a recent history (within the last year) of drug or alcohol abuse or dependence that in the judgment of the Investigator, would interfere with compliance with the requirements of the study.

Primary outcomes:
measure: To determine the efficacy of PTX-100 as determined by ORR.
timeFrame: 18 months from day of first treatment until disease progression, unacceptable toxicity, participant or Investigator decision.
Secondary outcomes:
measure: To further characterize the efficacy of PTX-100
timeFrame: Within 18 months after PTX-100 initial dose.
measure: Progression-free survival (PFS)
timeFrame: Within 18 months after PTX-100 initial dose.
measure: Time to response (TTR)
timeFrame: Within 18 months after PTX-100 initial dose.
measure: Overall survival (OS)
timeFrame: Within 18 months after PTX-100 initial dose.
measure: Duration of response (DoR)
timeFrame: Within 18 months after PTX-100 initial dose.
measure: Complete response rate (CRR)
timeFrame: Within 18 months after PTX-100 initial dose.
measure: Pharmacokinetics (PK) of PTX-100: Cmax
timeFrame: Cycle 1: Day 1 and Day 5: pre-dose, 5 mins post-infusion, and at 1, 2, 4, 6, and 8 hours after dose. Day 2, 3 and 4: 24 hours after previous dose, bloods taken at Pre and at 5 mins post-infusion. Day 8; 72 hours after the Day 5 dose and prior to dosing.
measure: Pharmacokinetics (PK) of PTX-100: Tmax
timeFrame: Cycle 1: Day 1 and Day 5: pre-dose, 5 mins post-infusion, and at 1, 2, 4, 6, and 8 hours after dose. Day 2, 3 and 4: 24 hours after previous dose, bloods taken at Pre and at 5 mins post-infusion. Day 8; 72 hours after the Day 5 dose and prior to dosing.
measure: Pharmacokinetics (PK) of PTX-100: Cmin
timeFrame: Cycle 1: Day 1 and Day 5: pre-dose, 5 mins post-infusion, and at 1, 2, 4, 6, and 8 hours after dose. Day 2, 3 and 4: 24 hours after previous dose, bloods taken at Pre and at 5 mins post-infusion. Day 8; 72 hours after the Day 5 dose and prior to dosing.
measure: Pharmacokinetics (PK) of PTX-100: AUCtau
timeFrame: Cycle 1: Day 1 and Day 5: pre-dose, 5 mins post-infusion, and at 1, 2, 4, 6, and 8 hours after dose. Day 2, 3 and 4: 24 hours after previous dose, bloods taken at Pre and at 5 mins post-infusion. Day 8; 72 hours after the Day 5 dose and prior to dosing.
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Comprehensive Cancer Cente
state: Virginia
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Washington
city: Paris
country: France
facility: Hopital Saint Louis
state: Île-de-France
city: Milan
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario San Raffaele)
state: Milano
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero Universitaria di Bologna - Policlinico S. Orsola-Malpighi
city: Brescia
country: Italy
facility: Universita degli Studi Di Brescia-Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Study officials:
References: