Extranodal Natural Killer/T-Cell Lymphoma
Conditions
Keywords
ENKTL
Brief summary
This is a multicenter, single-arm, phase II study to evaluate the efficacy and safety of CS1001 monotherapy for Relapsed or Refractory Extranodal Natural Killer/ T Cell Lymphoma (ENKTL)
Detailed description
Eligible subjects with rr-NKTL after prior asparaginase-based chemotherapy or chemo radiotherapy are planned to receive CS1001 1200 mg intravenous infusion every three weeks until progression of disease, intolerable toxicity, consent withdrawn, death. The primary endpoint of this trial is objective response rate (ORR), as assessed by independent radiological review committee (IRRC) based on Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification.
Interventions
BIOLOGICALCS1001
monoclonal antibody
Sponsors
CStone Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject must have a histologically confirmed NKTL at study site. 2. Subject must have relapsed or refractory NKTL after prior asparaginase-based chemotherapy or chemo radiotherapy. 3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. 4. Subject must have at least one evaluable or measurable lesion per Lugano 2014 classification. 5. Subject must have adequate organ function and bone marrow function without severe hematopoietic disorder, or heart, lung, liver or kidney dysfunction or immune deficiency. 6. Subject must provide stained tumor tissue sections and corresponding pathological report or unstained tumor tissue sections (or tissue block) for central pathology review. 7. Subject with prior anti-cancer treatment can only be enrolled when the toxicity of prior anti-cancer treatment has recovered to baseline or ≤ Grade 1 according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
Exclusion criteria
1. Invasive natural killer leukemia. 2. Concomitant with hemophagocytic syndrome. 3. Primary site in central nervous system (CNS) or CNS involvement. 4. Subjects currently participating in other clinical studies or use of any investigational drug within 4 weeks prior to the first dose of CS1001. 5. Subjects who received systemic corticosteroid or any other immunosuppressive therapy within 14 days prior to the first dose of CS1001. 6. Subjects who had prior chemotherapy, immune therapy, biological therapy as systemic treatment for cancer, within 28 days prior to the first dose of CS1001. 7. Receipt of traditional medicinal herbal preparations with anti-tumor indications with 7 days prior to the first dose of CS1001. 8. Known history of human immunodeficiency virus (HIV) infection and/or acquired immune deficiency syndrome. 9. Subjects with active hepatitis B or C infection. 10. Subjects with active tuberculosis infection. 11. Subjects who received prior therapy with anti-PD-1, anti-PD-L1 or anti-CTLA-4 monoclonal antibody. 12. Female subjects who are pregnant or breast-feeding. For more information regarding trial participation, please contact at cstonera@cstonepharma.com
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Assessed by IRRC | From enrollment to end of follow-up, a median of 29 months | ORR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Response Rate (PRR) Assessed by IRRC | From enrollment to end of follow-up, a median of 29 months | PRR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| Time to Response (TTR) Assessed by Investigators | From enrollment to end of follow-up, a median of 29 months | TTR assessed by the investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| Time to Response (TTR) Assessed by IRRC | From enrollment to end of follow-up, a median of 29 months | TTR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| Number of Participants With Adverse Events | From enrollment to end of follow-up, a median of 29 months | — |
| Complete Response Rate (CRR) Assessed by IRRC | From enrollment to end of follow-up, a median of 29 months | CRR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| Objective Response Rate (ORR) Assessed by Investigators | From enrollment to end of follow-up, a median of 29 months | ORR assessed by investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| Complete Response Rate (CRR) by Investigators | From enrollment to end of follow-up, a median of 29 months | CRR assessed by investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| Partial Response Rate (PRR) Assessed by Investigators | From enrollment to end of follow-up, a median of 29 months | PRR assessed by the investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| Duration of Response (DoR) Assessed by Investigators | From enrollment to end of follow-up, a median of 29 months | DoR assessed by the investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| Duration of Response (DoR) Assessed by IRRC | From enrollment to end of follow-up, a median of 29 months | DoR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
Other
| Measure | Time frame | Description |
|---|---|---|
| 6-month Overall Survival (OS) Rate | 6 months | — |
| 6-months Progression-free Survival (PFS) Rate Assessed by Investigators | 6 months | 6-months PFS rate assessed by the investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
| 6-months PFS Rate Assessed by IRRC | 6 months | 6-months PFS rate assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| R/R ENKTL Participants received sugemalimab (CS1001) 1200 mg intravenously every 3 weeks (Q3W) | 80 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Achieved CR and completed 2 years of treatment | 1 |
| Overall Study | Adverse Event | 14 |
| Overall Study | Death | 1 |
| Overall Study | Dosing delayed over 9 weeks | 1 |
| Overall Study | Lack of Efficacy | 40 |
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | R/R ENKTL |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 66 Participants |
| Age, Continuous | 48.1 Years STANDARD_DEVIATION 12.68 |
| Baseline Bone Marrow Assessment Result Missing | 2 Participants |
| Baseline Bone Marrow Assessment Result Negative | 73 Participants |
| Baseline Bone Marrow Assessment Result Positive | 5 Participants |
| Central Pathology Confirmed ENKTL No | 1 Participants |
| Central Pathology Confirmed ENKTL Yes | 79 Participants |
| Eastern Cooperative Oncology Group Performance Status 0 | 21 Participants |
| Eastern Cooperative Oncology Group Performance Status 1 | 59 Participants |
| Epstein-Barr Virus (EBV) DNA at Screening Negative | 36 Participants |
| Epstein-Barr Virus (EBV) DNA at Screening Positive | 44 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Patient Status Refractory | 37 Participants |
| Patient Status Relapsed | 43 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 80 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 80 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 51 Participants |
| Stage of Extranodal Natural Killer/ T-cell Lymphoma at screening Stage I | 9 Participants |
| Stage of Extranodal Natural Killer/ T-cell Lymphoma at screening Stage II | 17 Participants |
| Stage of Extranodal Natural Killer/ T-cell Lymphoma at screening Stage IV | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 37 / 80 |
| other Total, other adverse events | 76 / 80 |
| serious Total, serious adverse events | 22 / 80 |
Outcome results
Primary
Objective Response Rate (ORR) Assessed by IRRC
ORR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: Two patients were excluded from analysis: one patient was not confirmed as ENKTL by central pathology, and the other patient was identified as having no measurable or evaluable disease at baseline by IRRC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | Objective Response Rate (ORR) Assessed by IRRC | 46.2 percentage of Participants |
Secondary
Complete Response Rate (CRR) Assessed by IRRC
CRR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: Two patients were excluded from analysis: one patient was not confirmed as ENKTL by central pathology, and the other patient was identified as having no measurable or evaluable disease at baseline by IRRC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | Complete Response Rate (CRR) Assessed by IRRC | 37.2 Percentage of participants |
Secondary
Complete Response Rate (CRR) by Investigators
CRR assessed by investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: One patient was excluded from the efficacy analysis set because the patient was not confirmed as ENKTL by central pathology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | Complete Response Rate (CRR) by Investigators | 30.4 Percentage of participants |
Secondary
Duration of Response (DoR) Assessed by Investigators
DoR assessed by the investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: One patient was excluded from the efficacy analysis set because the patient was not confirmed as ENKTL by central pathology.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R/R ENKTL | Duration of Response (DoR) Assessed by Investigators | 39.9 months |
Secondary
Duration of Response (DoR) Assessed by IRRC
DoR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: Two patients were excluded from analysis: one patient was not confirmed as ENKTL by central pathology, and the other patient was identified as having no measurable or evaluable disease at baseline by IRRC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R/R ENKTL | Duration of Response (DoR) Assessed by IRRC | 35.2 months |
Secondary
Number of Participants With Adverse Events
Time frame: From enrollment to end of follow-up, a median of 29 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| R/R ENKTL | Number of Participants With Adverse Events | TEAE Leading to Infusion Interruption | 4 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | Treatment-Emergent Adverse Event (TEAE) | 77 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | Treatment-Related Adverse Event (TRAE) | 63 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | Serious Adverse Event (SAE) | 22 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | Related SAE | 8 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | ≥G3 TEAE | 37 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | ≥G3 TRAE | 15 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | Infusion-related Reaction | 4 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | TEAE of special interest | 24 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | TEAE of special interest grade 3-5 | 2 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | TEAE Leading to Death | 5 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | TEAE Leading to Drug Permanently Discontinued | 14 Participants |
| R/R ENKTL | Number of Participants With Adverse Events | TEAE Leading to Treatment Cycle Delay | 22 Participants |
Secondary
Objective Response Rate (ORR) Assessed by Investigators
ORR assessed by investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: One patient was excluded from the efficacy analysis set because the patient was not confirmed as ENKTL by central pathology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | Objective Response Rate (ORR) Assessed by Investigators | 45.6 Percentage of participants |
Secondary
Partial Response Rate (PRR) Assessed by Investigators
PRR assessed by the investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: One patient was excluded from the efficacy analysis set because the patient was not confirmed as ENKTL by central pathology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | Partial Response Rate (PRR) Assessed by Investigators | 15.2 Percentage of participants |
Secondary
Partial Response Rate (PRR) Assessed by IRRC
PRR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: Two patients were excluded from analysis: one patient was not confirmed as ENKTL by central pathology, and the other patient was identified as having no measurable or evaluable disease at baseline by IRRC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | Partial Response Rate (PRR) Assessed by IRRC | 9.0 Percentage of participants |
Secondary
Time to Response (TTR) Assessed by Investigators
TTR assessed by the investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: One patient was excluded from the efficacy analysis set because the patient was not confirmed as ENKTL by central pathology.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R/R ENKTL | Time to Response (TTR) Assessed by Investigators | 2.8 months |
Secondary
Time to Response (TTR) Assessed by IRRC
TTR assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: From enrollment to end of follow-up, a median of 29 months
Population: Two patients were excluded from analysis: one patient was not confirmed as ENKTL by central pathology, and the other patient was identified as having no measurable or evaluable disease at baseline by IRRC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| R/R ENKTL | Time to Response (TTR) Assessed by IRRC | 2.8 months |
Other Pre-specified
6-month Overall Survival (OS) Rate
Time frame: 6 months
Population: One patient was excluded from the efficacy analysis set because the patient was not confirmed as ENKTL by central pathology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | 6-month Overall Survival (OS) Rate | 79.2 Percentage of participants |
Other Pre-specified
6-months PFS Rate Assessed by IRRC
6-months PFS rate assessed by the independent radiological review committee (IRRC) according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: 6 months
Population: Two patients were excluded from analysis: one patient was not confirmed as ENKTL by central pathology, and the other patient was identified as having no measurable or evaluable disease at baseline by IRRC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | 6-months PFS Rate Assessed by IRRC | 49.7 percentage of participants |
Other Pre-specified
6-months Progression-free Survival (PFS) Rate Assessed by Investigators
6-months PFS rate assessed by the investigators according to Criteria for Response Assessment of Lymphoma: Lugano 2014 Classification
Time frame: 6 months
Population: one patient was excluded from the efficacy analysis set because the patient was not confirmed as ENKTL by central pathology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R/R ENKTL | 6-months Progression-free Survival (PFS) Rate Assessed by Investigators | 39.1 Percentage of participants |