Phase 1/2 multicenter, open-label, dose-escalation study of IDP-121 in patients with relapsed/refractory hematologic malignancies (CASSANDRA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Idp Discovery Pharma S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

6 Jun 2023 → ongoing

Decision date (initial)

2024-12-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-519194-19-00

EudraCT number

2021-003993-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Efficacy

Dose-Escalation Phase (Phase 1):
To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of IDP-121 in patients with multiple myeloma (MM), B-cell lymphoma, and chronic lymphocytic leukemia (CLL).

Expansion Phase (Phase 2):
To evaluate the overall response rate (ORR) in patients with MM, B-cell lymphoma or CLL treated with IDP-121 at the recommended Phase 2 Dose (RP2D).

Secondary objectives 3

1. To determine additional efficacy objectives, including duration of response (DoR), time to progression (TTP), progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) at the RP2D.
2. To evaluate the safety of IDP-121 at the RP2D.
3. To determine the pharmacokinetic (PK) profile of IDP-121 in patients with CLL, B-cell lymphoma, and MM.

Conditions and MedDRA coding

Chronic lymphocytic leukemia (CLL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥18 years
2. Performance status (ECOG) ≤ 2
3. Life expectancy ≥3 months
4. Patient is, in the investigator’s opinion, willing and able to comply with the protocol requirements.
5. Patient has given voluntary written informed consent before performance of any studyrelated procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
6. Patients diagnosed with chronic lymphocytic leukemia (CLL), B-cell lymphomas, and multiple myeloma (MM) who are ineligible to receive the available treatments.
7. Adequate hematological or biochemical parameters as specified below a. Hemoglobin > 8.0 g/dl (without transfusion support within 7 days) b. Platelets count > 75 x109/L (without transfusional support within 7 days). In patients with bone marrow infiltration, the platelets count may be ≥50 x109/L. c. Absolute neutrophil count (ANC) > 0.75 x109/L (without G-CSF support within 7 days) d. Aspartate transaminase (AST): <2.5 x the upper limit range (in patients with no liver metastases or <5 x ULN in patients with liver metastases) e. Alanine transaminase (ALT): < 2.5 x the upper limit range (in patients with no liver metastases or <5 x ULN in patients with liver metastases) f. Total bilirubin: < 2 x the upper limit range. g. Calculated or measured creatinine clearance: >30 mL/min (calculated from the Cockcroft-Gault formula).
8. Left ventricular ejection fraction > 50% or above the Institutional Lower Limit of Normal (LLN), whichever is lower, determined by echocardiogram.

Exclusion criteria 14

1. Persistent clinically significant non-hematological toxicity related to previous treatments. The presence of alopecia and NCI-CTC grade <2 symptomatic peripheral neuropathy is allowed.
2. Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods (combined hormonal contraception associated with inhibition of ovulation; progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinenence).
3. History of any other neoplastic disease in the last five years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site)
4. History of clinically significant hypotension.
5. History of clinically significant allergic or hyper-sensitivity reactions.
6. History or known clinically significant vascular disease or known high risk of vascular disease (as assessed by the treating physician) including (but not limited to): - Thromboembolism - Peripheral arterial disease - Vasculitis
7. Other relevant diseases or adverse clinical conditions: - Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study. - Uncontrolled arterial hypertension or cardiac arrhythmias (i.e., requiring a change in medication within the last 3 months or hospital admission within the past 6 months). - History of significant neurological or psychiatric disorders
8. Clinically significant or active infection.
9. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)
10. The patient is known to be human immunodeficiency virus (HIV) positive, unless the patient is on antiviral therapy with HIV RNA levels <50 copies/mL; Hepatitis B surface antigen-positive or active hepatitis C infection, unless treated with undetectable hepatitis B DNA or hepatitis C RNA levels; or active CMV infection (IgM positive).
11. Concomitant anti-tumor therapy within 14 days prior to Day 1 of Cycle 1.
12. Prior allogeneic transplantation in the last 3 months or currently active GVHD with immunosuppressive treatment
13. Limitation of the patient’s ability to comply with the treatment or follow-up protocol.
14. If a COVID-19 vaccine is administered, it should be done >72 hours prior to study treatment initiation or after the completion of the dose-limiting toxicity (DLT) period (if patient is participating in the dose-escalation phase”).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Maximum tolerated dose (MTD): based on the incidence of DLTs observed at the end of Cycle 1 (28 days).
2. Recommended phase 2 dose (RP2D): dose used in subsequent Expansion phase. The RP2D will be determined in discussion with the Investigators and the Sponsor based on safety (dose limiting toxicity), PK, PD, and any cumulative toxicity after multiple cycles.
3. Overall response rate (ORR) for CLL, MM and Lymphomas, respectively.

Secondary endpoints 7

1. Duration of response (DoR), defined as the time from documentation of disease response to disease progression.
2. Time to progression (TTP), time from the first treatment day to objective disease progression; does not include deaths.
3. Progression-free survival (PFS) defined as the interval between the first treatment day to the first sign of disease progression or death from any cause.
4. Event-free survival (EFS) defined as the interval time between the first treatment day to disease progression, death, or discontinuation of treatment from any cause (e.g., toxicity, patient preference, or initiation of a new treatment without documented progression).
5. Overall survival (OS) defined as the interval between the first treatment day to death from any cause.
6. Safety endpoints: Vital signs, Physical examination, Hematology, Biochemistry, Urinalysis, Electrocardiograms (ECG), All grades AEs and SAEs
7. Pharmacokinetics parameters: AUClast, Cmax, CL, Css, Ctrough, Ke, t1/2, Tmax, Vd

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Idp Discovery Pharma S.L.

Sponsor organisation

Idp Discovery Pharma S.L.

Address

Carrer De Baldiri Reixac 4, Poligono Industrial Parc Cientific De Barcelona Poligono Industrial Parc Cientific De Barcelona

City

Barcelona

Postcode

08028

Country

Spain

Scientific contact point

Organisation

Idp Discovery Pharma S.L.

Contact name

Clinical Operations Manager

Public contact point

Organisation

Idp Discovery Pharma S.L.

Contact name

Clinical Operations Manager

Locations

1 EU/EEA country · 12 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

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 4 files

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

Application history

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