Study of IPH4102 alone or in combination with chemotherapy in patients with Advanced T-cell Lymphoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Innate Pharma

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Mar 2019 → 23 Dec 2025

Decision date (initial)

2024-05-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Innate Pharma SA

External identifiers

EU CT number

2023-507777-18-00

EudraCT number

2018-003969-33

ClinicalTrials.gov

NCT03902184

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Safety

To evaluate the objective response rate (ORR).

Secondary objectives 4

1. 1. To characterize the safety and tolerability of IPH4102.
2. 2. To assess quality of life (QoL).
3. 3. To evaluate other clinical activity endpoints: ORR using blinded central review (Cohort 1 only), duration of response (DOR), progression free survival (PFS) and overall survival (OS).
4. 4. To evaluate the pharmacokinetics (PK) and immunogenicity of IPH4102.

Conditions and MedDRA coding

Advanced T-Cell Lymphomas (TCL), i.e. Cutaneous T Cell Lymphomas (CTCL) CTCL subtypes under investigation: relapsed/refractory Sézary Syndrome (SS), stage IB to IV Mycosis Fungoides (MF).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. SS patients (Cohort 1): 1. Relapsed and/or refractory stage IVA, IVB SS who have received at least two prior systemic therapies.
2. SS patients (Cohort 1): 2. Prior treatment with mogamulizumab.
3. SS patients (Cohort 1): 3. Patients should have blood stage B2 at screening based on central evaluation by flow cytometry.
4. SS patients (Cohort 1): 4. Feasibility of obtaining at least one skin biopsy at screening.
5. MF patients (Cohorts 2 and All comers): 5. Relapsed and/or refractory stage IB, IIA, IIB, III, IV MF.
6. MF patients (Cohorts 2 and All comers): 6. Only for Cohort 2: KIR3DL2 expression in at least one expressing skin lesion based on central evaluation by IHC.
7. MF patients (Cohorts 2 and All comers): 7. Patients should have received at least two prior systemic therapies.
8. MF patients (Cohorts 2 and All comers): 8. Feasibility of obtaining at least one skin biopsy at screening.
9. 9. Male or Female, at least 18 years of age.
10. 10. ECOG performance status ≤2.
11. 11. The patient must have a minimum wash-out period of 3 weeks between the last dose of prior systemic therapy and the first dose of IPH4102.
12. 12. Patients should have recovered from all non-hematological adverse events related to priortherapy to ≤ grade 1 except for alopecia.
13. 13. Adequate baseline laboratory data: Hematology: - Hemoglobin >9 g/dL, - Absolute neutrophil count (ANC) ≥1,500/µL, - Platelets ≥100,000/µL, Biochemistry: - Bilirubin ≤1.5 X upper limit of normal (ULN) or ≤3 X ULN for patients with Gilbert’s disease, - Serum creatinine ≤1.5 X ULN, - Creatinine clearance ≥30 mL/min, calculated with the Cockcroft & Gault formula, - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 X ULN.
14. 14. Women of childbearing potential (WOCBP): Premenopausal females who had at least one menstrual cycle in the past 12 months and capable to become pregnant. They must have a negative serum beta-HCG pregnancy test result within seven days from start of treatment.
15. 15. Women of childbearing potential and all men (and their female partners of childbearing potential) who are sexually active must agree to use adequate method of contraception at study entry, during treatment and for at least 9 months (270 days) following the last dose of study drug.
16. 16. Signed informed consent form prior to any protocol-specific procedures.

Exclusion criteria 17

1. 1. Patients with evidence of large cell transformation (LCT) based on central histologic evaluation at screening.
2. 10. Patients who have Hepatitis B Virus infection determined as HBsAg positive and/or Hepatitis C Virus infection determined as detection of HCV RNA in serum or plasma by a sensitive quantitative molecular method.
3. 11. Known or tested positive for human immunodeficiency virus (HIV).
4. 2. Receipt of live vaccines within 4 weeks prior the treatment.
5. 3. Central nervous system (CNS) lymphoma involvement.
6. 4. Prior administration of IPH4102.
7. 5. Concurrent enrollment in another clinical trial, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
8. 6. Autologous stem cell transplantation less than 3 months prior to enrollment.
9. 7. Prior allogenic transplantation.
10. 8. Patients who have undergone major surgery ≤ 4 weeks prior to study entry.
11. 9. Patients with known NCI CTCAE grade 3 or higher active systemic or cutaneous viral, bacterial, or fungal infection.
12. 12. Patients with a history of other malignancies during the past five years apart from the disease subject of this study. The following are exempt from the five-year limit: nonmelanoma skin cancer, lymphomatoid papulosis, resected thyroid cancer, biopsy-proven cervical intraepithelial neoplasia, Ductal carcinoma in situ (DCIS) or cervical carcinoma in situ.
13. 13. Pregnant or breastfeeding women.
14. 14. Known clinically significant cardiovascular disease or condition, including: - Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) Functional Classification; - Any uncontrolled arrhythmia (per the investigator’s discretion); - Uncontrolled hypertension (per the investigator’s discretion).
15. 15. Patients with autoimmune disease on systemic immunosuppressive treatment.
16. 16. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment and/or comply with study protocol.
17. 17. Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR). ORR is defined as the proportion of patients with complete or partial response.

Secondary endpoints 8

1. 1. Safety Assessment: - AEs, SAEs, change in clinical laboratory evaluations and vital signs.
2. 3. Quality of life: obtained with the patient-reported VAS score for pruritus and QoL questionnaire SkinDex29.
3. 4. Pharmacokinetic (PK) Assessment: Individual IPH4102 serum concentration.
4. 5. Immunogenic potential of IPH4102: Immunogenicity results for each patient.
5. 2.a. Other antitumor activity endpoints: - Duration of response measured from the first documentation of objective response (if subsequently confirmed) to the event of disease progression or death.
6. 2.b. Other antitumor activity endpoints: - Objective response rate (ORR) review of disease response by central review (Cohort 1 only).
7. 2.c. Other antitumor activity endpoints: - Progression free survival (PFS) from the start of IPH4102 administration to documented progression or death from any cause.
8. 2.d. Other antitumor activity endpoints: - Overall Survival (OS) measured from the start of IPH4102 administration to death from any cause.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Innate Pharma

Sponsor organisation

Innate Pharma

Address

117 Avenue De Luminy

City

Marseille

Postcode

13009

Country

France

Scientific contact point

Organisation

Innate Pharma

Contact name

Medical Director

Public contact point

Organisation

Innate Pharma

Contact name

Medical Director

Third parties 9

Locations

6 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 48 files

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

Application history

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