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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Telios Pharma Inc., Telios Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Jan 2021 → 31 Jul 2025

Decision date (initial)

2024-12-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Telios Pharma, Inc.

External identifiers

EU CT number

2024-516691-14-00

EudraCT number

2016-000286-23

WHO UTN

U1111-1313-2277

ClinicalTrials.gov

NCT02825836

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy, Pharmacogenetic, Safety, Therapy

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

Secondary objectives 5

1. To determine the CR/ CRi rate
2. To assess the efficacy of TL-895 in combination with navtemadlin by DOR
3. To evaluate the safety and tolerability of TL-895 in combination with navtemadlin
4. To characterize the PK profile of TL-895 and navtemadlin
5. To determine the rate of minimal residual disease (MRD)

Conditions and MedDRA coding

B Cell Malignancies and Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adults ≥18 years of age
2. Arms 1 and 2 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)
3. Arms 3 and 4 - Subject population (treatment-naive CLL or treatment-naïve SLL)
4. Arm 5 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)
5. Arm 6 - Subject population (treatment-naive CLL or treatment-naïve SLL)
6. Arm 7 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)
7. For the full list of inclusion criteria please refer to the Protocol

Exclusion criteria 18

1. 1. Prior anticancer treatment with any BTK, MDM2 inhibitor or PI3K inhibitor
2. 10. Subjects with indwelling surgical drains (e.g., peritoneal, CNS, or pleural)
3. 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.
4. 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.
5. 13. Grade 2 or higher QTc prolongation (> 480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [v 5.0]).
6. 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
7. 15. Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV)
8. 16. Subjects with known history of human immunodeficiency virus (HIV)
9. 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.
10. 18. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
11. 2. Known history of central nervous system lymphoma or leukemia
12. 20. Women who are pregnant or breastfeeding.
13. 3. History of Richter’s transformation or prolymphocytic leukemia
14. 4. 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
15. 5. Arms 3, 4 and 6 – Any prior therapy used for treatment of CLL/SLL
16. 8. Received major surgical intervention within 28 days prior to first dose of study treatment, or history of major organ transplant.
17. 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
18. For the full list of exclusion criteria please refer to the Protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 5

1. CR/CRi rate, defined as the proportion of subjects achieving CR/CRi based on iwCLL response criteria
2. DOR, defined as time from initial response to disease progression or death from any cause
3. 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
4. • TL-895 PK parameters, including but not limited to: − Predose concentration (C0h) − Concentration at 2 hours post-dose (C2h) − Cmax − Tmax − AUC
5. BTK occupancy in PBMCs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Telios Pharma Inc.

Sponsor organisation

Telios Pharma Inc.

Address

275 Shoreline Drive Suite 325

City

Redwood City

Postcode

94065-1407

Country

United States

Scientific contact point

Organisation

Telios Pharma Inc.

Contact name

Clinical Development Operations

Public contact point

Organisation

Telios Pharma Inc.

Contact name

Clinical Development Operations

Third parties 14

Telios Pharma Inc.

Sponsor organisation

Telios Pharma Inc.

Address

275 Shoreline Drive Suite 325

City

Redwood City

Postcode

94065-1407

Country

United States

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications