Phase I/II, First in Human, Dose Escalation Trial of TL-895 Monotherapy in Subjects with Relapsed/Refractory B-Cell Malignancies and Expansion of TL-895 Monotherapy and Combination Therapy with Navtemadlin in Treatment-Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Subjects and Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Small Lymphocytic Lymphoma

Phase 1/2

Active, not recruiting

• Conditions: B Cell Malignancies and Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Registration Number: 2024-516691-14-00
• Lead Sponsor: Telios Pharma Inc.

Brief Summary

For dose expansion, Part 2:

Arms 1, 2, 3 and 4

To determine the overall response rate (ORR) based on International Workshop on Chronic Lymphocytic Leukemia (iwCLL) response criteria per Investigator assessment

Arms 5, 6 and 7

To determine the ORR based on iwCLL response criteria per Investigator assessment

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-12-14
• Last Update Posted: 2025-05-09

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 69

Inclusion Criteria

Adults ≥18 years of age

Arms 1 and 2 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)

Arms 3 and 4 - Subject population (treatment-naive CLL or treatment-naïve SLL)

Arm 5 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)

Arm 6 - Subject population (treatment-naive CLL or treatment-naïve SLL)

Arm 7 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)

For the full list of inclusion criteria please refer to the Protocol

Exclusion Criteria

1. Prior anticancer treatment with any BTK, MDM2 inhibitor or PI3K inhibitor

2. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.

3. Known history of central nervous system lymphoma or leukemia

4. Women who are pregnant or breastfeeding.

5. History of Richter’s transformation or prolymphocytic leukemia

6. Arms 1, 2, 5 and 7 - Prior therapy with: • Anticancer treatment with chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, or with any other anticancer therapy within 28 days prior to first dose of study treatment. • Any investigational agent within 28 days prior to first dose of study treatment. Participation in observational study is permitted. • Allogeneic stem cell transplant or active graft versus host disease following allogeneic transplant within 6 months prior to first dose of study treatment. • Autologous stem cell transplant within the last 3 months prior to first dose of study treatment

7. Arms 3, 4 and 6 – Any prior therapy used for treatment of CLL/SLL

8. Received major surgical intervention within 28 days prior to first dose of study treatment, or history of major organ transplant.

9. Subjects with active fever (temperature higher than 38.2°C [100.8°F]) within 14 days prior to the first dose of study treatment

For the full list of exclusion criteria please refer to the Protocol

10. Subjects with indwelling surgical drains (e.g., peritoneal, CNS, or pleural)

11. Having history of difficulty of swallowing, gastric or small bowel surgery with history of malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the study treatment.

12. Uncontrolled intercurrent illness including, but not limited to clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; unstable ventricular arrhythmia; or psychiatric illness/ social situations that would limit compliance with study requirements.

13. Grade 2 or higher QTc prolongation (> 480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [v 5.0]).

14. Subjects with uncontrolled bacterial, fungal, parasitic, or viral infection. Subjects with acute bacterial infections requiring antibiotic use should not enroll until the infection is stable in the judgement of the treating physician; these subjects may be on antibiotics at time of screening

15. Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV)

16. Subjects with known history of human immunodeficiency virus (HIV)

17. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Dose Expansion, Part 2 - ORR, defined as the proportion of subjects achieving CR, CRi, nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PR-L) at any time while on the study based on iwCLL response criteria, as assessed by investigators.		Dose Expansion, Part 2 - ORR, defined as the proportion of subjects achieving CR, CRi, nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PR-L) at any time while on the study based on iwCLL response criteria, as assessed by investigators.

Secondary Outcome Measures

Name	Time	Method
CR/CRi rate, defined as the proportion of subjects achieving CR/CRi based on iwCLL response criteria		CR/CRi rate, defined as the proportion of subjects achieving CR/CRi based on iwCLL response criteria
DOR, defined as time from initial response to disease progression or death from any cause		DOR, defined as time from initial response to disease progression or death from any cause
Analyses of the safety and tolerability endpoints will include the following measurements or assessments: − Incidence, nature, severity of treatment-emergent AEs (TEAEs), and deaths, including the cause of death, from Screening up to the End of Treatment visit − Clinical laboratory measurements, ECG measures, vital signs, ECOG performance status from Screening up to the End of Treatment visit		Analyses of the safety and tolerability endpoints will include the following measurements or assessments: − Incidence, nature, severity of treatment-emergent AEs (TEAEs), and deaths, including the cause of death, from Screening up to the End of Treatment visit − Clinical laboratory measurements, ECG measures, vital signs, ECOG performance status from Screening up to the End of Treatment visit
• TL-895 PK parameters, including but not limited to: − Predose concentration (C0h) − Concentration at 2 hours post-dose (C2h) − Cmax − Tmax − AUC		• TL-895 PK parameters, including but not limited to: − Predose concentration (C0h) − Concentration at 2 hours post-dose (C2h) − Cmax − Tmax − AUC
BTK occupancy in PBMCs		BTK occupancy in PBMCs

Trial Locations

Locations (6)

Heves Varmegyei Markhot Ferenc Oktatokorhaz Es Rendelointezet; 🇭🇺 Eger, Hungary

University Of Debrecen; 🇭🇺 Debrecen, Hungary

Medicover Integrated Clinical Services Sp. z o.o.; 🇵🇱 Torun, Poland

Szpital Wojewodzki W Opolu Sp. z o.o.; 🇵🇱 Opole, Poland

Pratia S.A.; 🇵🇱 Poznan, Poland

Centrum Onkologii Ziemi Lubelskiej Im. Sw. Jana Z Dukli; 🇵🇱 Lublin, Poland

Heves Varmegyei Markhot Ferenc Oktatokorhaz Es Rendelointezet

🇭🇺Eger, Hungary

Balázs Tajti

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