Clinical trial NCT05020639: A Study of TQB3820 in Patients With Hematological Malignancies
Official title: A Phase I Study to Evaluate the Tolerability and Pharmacokinetics of TQB3820 in Relapsed or Refractory Multiple Myeloma (R/R MM) or Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma (R/R B-NHL)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hematological Malignancies
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-25
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TQB3820 is a novel cereblon-modulating agent. Upon binding to cereblon, a substrate receptor in the cullin4 E3 ligase complex, TQB3820 promotes recruitment, ubiquitination, and subsequent proteasomal degradation of the hematopoietic transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). Modulation of Aiolos and Ikaros expression has the potential to correct multiple aspects of the immune dysregulation mediated by B cells.


Eligibility criteria: Inclusion Criteria:

1. For Multiple Myeloma cohort

   1. Patients must have received at least 2 prior therapies;
   2. Measurable levels of myeloma paraprotein

      1. M-protein in serum \>5 g/L;
      2. M-protein in urine \>200mg/24h;
      3. Light chain Multiple Myeloma without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 100 mg/L and abnormal serum immunoglobulin kappa lambda free light chain ratio.
2. For Indolent B-NHL

   1. Progressed after standard treatment or no standard treatment with an established survival benefit is available;
   2. Imaging in screening showing at least one measurable lesion; In patients with CLL/SLL, circulating lymphocytes \>= 5.0 × 10\^9/L or lesions greater than 1.5 cm.
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
4. Life expectancy \>=3 months;
5. Adequate organ/system function;
6. Female patients of childbearing age should agree to use contraceptive measures during the study period and for at least 6 months after study is stopped; male patients should agree to use contraception during the study period and for at least 6 months after study is stopped;

Exclusion Criteria:

1. Patients received allogenic haemopoietic stem cell transplantation, or autologous stem cell transplantation within 3 months;
2. Diagnosed and/or treated additional malignancy within 3 years before the first dose;
3. With factors affecting oral medication;
4. Toxicity that is \>=Grade 2 caused by previous cancer therapy;
5. Patients with congenital bleeding or coagulopathy, or are being treated with anticoagulants;
6. Patients with uncontrolled infections;
7. Has received surgery, chemotherapy, radiotherapy or other anticancer therapies 2 weeks before the first dose;
8. Has received Chinese patent medicines with anti-tumor indications that National Medical Products Administration(NMPA) approved within 2 weeks before the first dose;
9. Pleural effusion, pericardial effusion or ascites that cannot be controlled and need repeated drainage;
10. Central nervous system metastases;
11. Has participated in other clinical studies within 4 weeks before the first dose;
12. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: up to 18 months
measure: Maximum Tolerated Dose (MTD)
timeFrame: up to 18 months
measure: Recommended Phase II Dose (RP2D)
timeFrame: up to 18 months
measure: Adverse Events (AEs)
timeFrame: Baseline up to 24 months
Secondary outcomes:
measure: Maximum (peak) plasma drug concentration (Cmax)
timeFrame: Hour 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on single dose ; Hour 0(pre-dose) of day1, day8, day15, day22 on multiple dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on multiple dose of day28)
measure: Time to reach maximum(peak )plasma concentration following drug administration (Tmax)
timeFrame: Hour 0(pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on single dose ; Hour 0(pre-dose) of day1, day8, day15, day22 on multiple dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on multiple dose of day28)
measure: Elimination half-life (t1/2)
timeFrame: Hour 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on single dose ; Hour 0 (pre-dose) of day1, day8, day15, day22 on multiple dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on multiple dose of day28)
measure: Overall response rate (ORR)
timeFrame: Baseline up to 24 months
measure: Clinical benefit rate (CBR)
timeFrame: Baseline up to 24 months
measure: Time to response (TTR)
timeFrame: Baseline up to 24 months
measure: Duration of Response (DOR)
timeFrame: Baseline up to 24 months
measure: Progression-free survival (PFS)
timeFrame: Baseline up to 24 months
measure: Overall survival (OS)
timeFrame: Baseline up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Affiliated Beijing Chaoyang Hospital of Capital Medical University
state: Beijing
city: Tianjin
country: China
facility: Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
state: Tianjin
Study officials:
References: