Solid Tumors
Conditions
Keywords
Dose Escalation, Dose Expansion, BGB-A317, BGB-290, Tislelizumab, Pamiparib
Brief summary
This trial studied the safety, pharmacokinetics, and antitumor activity of the anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) BGB-A317 (tislelizumab) in combination with the poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor BGB-290 (pamiparib) in participants with advanced solid tumors.
Interventions
BIOLOGICALTislelizumab
DRUGPamiparib
Sponsors
Myriad Genetic Laboratories, Inc.
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants voluntarily agreed to participate by giving written informed consent. 2. Must have received standard of care in the primary treatment of their disease. 3. Participants who had the below specified histologically confirmed malignancies that had progressed to the advanced or metastatic stage: 1. In Part A, the participants must have had an advanced malignancy, including but not limited to high-grade serous cancer of the ovary, fallopian tube, or peritoneum, triple negative breast cancer, small cell lung cancer (SCLC), primary peritoneal cancer, and any tumor likely to harbor DNA damage repair deficiencies susceptible to treatment with a PARP inhibitor or likely to be responsive to a PD-1 blocker. 2. In Part B, the participants recruited to 1 of the 8 expansion arms must have had advanced solid tumors of the following types: Arm 1: Participants with relapsed, platinum-sensitive high-grade epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) must have met the following criteria: i. Must have had at least 2 prior platinum-containing treatments in any treatment setting. ii. Must have had platinum-sensitive recurrent disease and must not have progressed (by Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1 criteria) within 6 months of the completion of the last platinum-containing line of treatment. • Note: Participants may have received additional non-platinum-based chemotherapy for recurrence after prior last platinum-containing regimen if the criteria for platinum sensitivity were met. iii. Arm 1a: Participants with relapsed, platinum-sensitive high-grade EOC with either known deleterious or suspected deleterious germline or somatic breast cancer susceptibility gene 1/2 (BRCA1/2) mutations or with homologous recombination deficiency (HRD). • If HRD or BRCA1/2 mutation status from archival tissue was unknown or had not been previously evaluated, then the archival tissue must have undergone tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result was BRCA1/2 or HRD positive, the participant was eligible for enrollment in Arm 1a. iv. Arm 1b: Participants with relapsed, platinum-sensitive high grade EOC who otherwise met the above criteria and were without known germline or somatic BRCA1/2 mutations and without HRD mutation. Arm 2: Participants with triple negative breast cancer must have met the following criteria: i. 0-1 prior platinum-containing treatment in any treatment setting. • Note: participants could have received additional therapy after the last platinum-containing line of treatment if the other eligibility criteria were met. ii. Participants who received at least 1 prior treatment but not more than 3 prior lines of treatment in the advanced or metastatic setting. iii. Known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or with documented HRD. • If HRD or BRCA1/2 mutation status from archival tissue was unknown or had not been previously evaluated, then the archival tissue must have undergone tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result was HRD positive, then the participant was eligible for enrollment in Arm 2. • If archival tissue was not available and the participant submitted a fresh tumor biopsy, then the diagnostic test needed to demonstrate somatic BRCA1/2 mutation or HRD positivity. Arm 3: Participants with metastatic castration-resistant prostate cancer, including but not limited to mutations in homologous recombination (HR) pathways and/or defined by HRD algorithms, and must have met the following criteria: i. May be either chemotherapy-naïve, but must have received prior abiraterone acetate and/or enzalutamide treatment, or have previously had no more than 2 taxane-based chemotherapy lines of treatment, including docetaxel and carbazitaxel. If docetaxel was used more than once, this was considered as 1 line of treatment. ii. At least 2 weeks since the completion of prior flutamide, bicalutamide, and nilutimide, or enzalutamide and abiraterone treatment. iii. Documented prostate cancer with one of the following: * Surgically or medically castrated. The testosterone levels did not need to be checked if the participant had undergone surgical castration for \> 4 months. Participants receiving chemical castration should have had testosterone levels checked at baseline and confirmed to be in the castrate levels (\< 0.5 ng/mL or 1.735 nM). In all cases, the luteinizing hormone-releasing hormone antagonist/agonist was to be continued in these participants. * Participants with only non-measurable bone lesions must have had disease progression based on Prostate Cancer Clinical Trials Working Group with 2 or more new lesions or have had prostate-specific antigen progression before enrolment. iv. Known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or with documented HRD. * If HRD or BRCA1/2 mutation status from archival tissue was unknown or had not been previously evaluated, then the archival tissue must have undergone tissue screening using a validated diagnostic test to determine eligibility. If the diagnostic test result was HRD positive, then the participant was be eligible for enrollment in Arm 3. * If archival tissue was not available and the participant summitted a fresh tumor biopsy, then the diagnostic test needed to demonstrate somatic BRCA1/2 mutation or HRD positivity. Arm 4: Participants with extensive-stage disease SCLC must have met the following criteria: i. Received at least 1 and not more than 2 prior lines of treatment; ii. At least 1 prior line of treatment must have contained a platinum agent Arm 5: Participants with human epidermal growth factor receptor-2 (HER2)-negative gastric or gastroesophageal junction cancer must have met the following criteria: i. May have received at least 1 and not more than 2 prior lines of treatment Arm 6: Participants with locally advanced or metastatic urothelial (muscle-invasive bladder, ureter, urethra, or renal pelvis) cancer must have met the following criteria: i. Received at least 1 and not more than 2 prior lines of treatment in the advanced or metastatic disease setting; ii. At least 1 prior line of treatment must have contained a platinum agent Arm 7: Participants with advanced or metastatic pancreatic adenocarcinoma must have met the following criteria: i. Received at least 1 but not more than 2 lines of treatment in either an advanced or metastatic setting; ii. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent; iii. Participants with known deleterious germline or somatic BRCA1/2 mutation could be considered for the study even if platinum naïve. Arm 8: (Note: Closed to enrollment) Participants with advanced or metastatic recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix and participants with tumors known to be mismatch repair deficient or HRD positive) must have met the following criteria: i. Participants with a complete response, partial response, or stable disease from at least 1 prior platinum-containing treatment in any treatment setting; ii. The Sponsor medical monitor would approve tumor types for Arm 8 prior to screening. • Note: Excluded tumor types included participants with bone or soft tissue sarcoma; central nervous system (CNS) malignancies; colorectal cancer (except microsatellite instability-high colorectal cancer is permitted); cutaneous or ocular melanoma; hematologic malignancies; HER2-negative breast cancer without BRCA mutation; mesothelioma, papillary, follicular, medullary or Hürthle cell thyroid cancer; unknown primary malignancy. 4. Participants who were treated with chemotherapy or any investigational therapies, if eligible, must have completed at least 4 weeks or at least 5 half-lives (whichever is longer, but no less than 3 weeks) before the study drug administration, and all adverse events (AEs) had either returned to baseline or stabilized. 5. At least 2 weeks from palliative radiotherapy. 6. Participants must have had archival tumor tissue or agree to a tumor biopsy for mutation and biomarkers analysis unless previously discussed with Sponsor's medical monitor or its designee (fresh tumor biopsies were recommended at baseline in participants with readily accessible tumor lesions and who consented to the biopsies). Participants with ovarian, fallopian tube, primary peritoneal, or breast cancer in Part A and all participants enrolled in Part B must also have agreed to provide fresh blood sample at the baseline for the evaluation of BRCA mutations and/or confirmation of prior BRCA results or other HR deficiency mutations, even if it was previously tested. 7. Participants must have had measurable disease as defined in RECIST v1.1. Participants with metastatic castration-resistant prostate cancer and epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer may have used separate disease-specific criteria. 8. Male or female ≥ 18 years of age on the day of signing informed consent. 9. Must have had an Eastern Cooperative Oncology Group Performance Status ≤ 1. 10. Must have had a life expectancy ≥ 12 weeks. 11. Must have had adequate organ function. 12. Females of childbearing potential must have been willing to use a highly effective method of birth control for the duration of the study, and for at least 6 months after the last dose of investigational drug, and have had a negative serum pregnancy test within 7 days of the first dose of study drug(s). 13. Non-sterile males and their female partners must have been willing to use a highly effective method of birth control for the duration of the study and for at least 6 months after the last dose of investigational drug. Nonsterile males must have avoided sperm donation for the duration of the study and for at least 6 months after last study drug. 14. Females must have agreed not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration. Key
Exclusion criteria
1. Participants with ovarian cancer who have platinum-resistant/refractory disease, defined as progressive disease at the first tumor assessment while receiving platinum-containing chemotherapy. 2. Participant had history of severe hypersensitivity reactions to other mAbs. 3. Any major surgery within 28 days before first dose of study drugs. 4. Prior allogeneic stem cell transplantation or organ transplantation. 5. Participants with toxicities (as a result of prior anticancer therapy) that had not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (for example, alopecia, neuropathy and specific laboratory abnormalities). 6. Concurrent participation in another clinical trial. 7. Prior malignancy within the previous 2 years except for locally curable non-melanoma dermatologic cancers that had been apparently cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the skin, cervix, breast, bladder, or prostate. 8. Symptomatic CNS metastasis or leptomeningeal disease. Note: Baseline magnetic resonance imaging of the brain and spinal cord was required for SCLC participants enrolled in Arm 4 if they had a history of CNS disease. Note: Participants with previously treated CNS metastatic disease were eligible for any arm if CNS metastatic disease was asymptomatic, clinically stable, and did not require corticosteroids or anticonvulsants within a minimum of 4 weeks of enrollment. 9. Prior therapies targeting PD-1, programmed death-ligand 1 (PD-L1), or PARP. 10. Active autoimmune diseases or history of autoimmune diseases that may have relapsed. Note: Participants with the following diseases were not excluded and may have proceeded to further screening: 1. Controlled Type I diabetes; 2. Hypothyroidism managed with no treatment other than with hormone replacement therapy; 3. Controlled celiac disease; 4. Skin diseases not requiring systemic treatment (for example, vitiligo, psoriasis, alopecia); 5. Any other disease that was not expected to recur in the absence of external triggering factors. 11. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 2 weeks of the study drug administration. Note: Participants who were currently or had previously been on any of the following steroid regimens were not excluded: 1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent); 2. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption; 3. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (for example, for contrast dye allergy) or for the treatment of a non-autoimmune condition (for example, delayed-type hypersensitivity reaction caused by contact allergen). 12. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, et cetera. 13. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, et cetera. 14. History of non-viral hepatitis or cirrhosis. 15. Positive human immunodeficiency virus status. 16. A known history of hepatitis B virus or hepatitis C virus infection. 17. History of alcohol abuse. 18. Underlying medical conditions or alcohol or drug abuse or dependence that, in the investigator's opinion, would be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs; or insufficient compliance during the study according to investigator's judgement. 19. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening, or otherwise altering the product formulation. Participants should not have had gastrointestinal illnesses that would have precluded the absorption of pamiparib, which was an oral agent. 20. Had been administered a live vaccine within 4 weeks (28 days) of initiation of study therapy. 21. Any of the following cardiovascular criteria: 1. Current evidence of cardiac ischemia; 2. Current symptomatic pulmonary embolism; 3. Acute myocardial infarction ≤ 6 months prior to Day 1; 4. Heart failure of New York Heart Association Classification III or IV ≤ 6 months prior to Day 1; 5. Grade ≥ 2 ventricular arrhythmia ≤ 6 months prior to Day 1; 6. History of cerebrovascular accident within 6 months before first dose of study drugs. 22. Use or had anticipated need for food or drugs known to be strong or moderate cytochrome P450 (CYP)3A inhibitors or strong CYP3A inducers ≤ 10 days (or ≤ 5 half-lives, whichever is shorter) prior to Day 1. Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number Of Participants Experiencing Adverse Events (AEs) | From Day 1 up to 4 years and 7 months | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
| Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) | 21 days following the first dose of tislelizumab and pamiparib in Cycle 1 | DLT was defined as an AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and occurs during the first 21 days following the first dose of tislelizumab and pamiparib in Cycle 1 and meets protocol-specified criteria. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
| Part B: Objective Response Rate (ORR) | Starting from Day 1 until disease progression (up to 4 years and 7 months) | ORR was defined as the percentage of participants with a best overall response of complete response (CR) and partial response (PR). |
| Part B: Progression-free Survival (PFS) | Starting from Day 1 until disease progression (up to 4 years and 7 months) | PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first. |
| Part B: Duration Of Response (DOR) | Starting from Day 1 until disease progression (up to 4 years and 7 months) | DOR, defined as the time from the first determination of an objective response, was assessed by investigator per Response Evaluation Criteria in Solid Tumors v1.1 until the first documentation of progression or death, whichever occurred first. Results are reported only for arms with responders. |
| Part B: Disease Control Rate (DCR) | Starting from Day 1 until disease progression (up to 4 years and 7 months) | DCR was defined as the percentage of participants with a best overall response of CR, PR, and stable disease (SD). |
| Part B: Clinical Benefit Rate (CBR) | Starting from Day 1 until disease progression (up to 4 years and 7 months) | CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks. |
| Part B: Overall Survival (OS) | From Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months) | OS was defined as the time from the date of first dose of study drug to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: CBR | Starting from Day 1 until disease progression (up to 4 years and 7 months) | CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks. |
| Part A: OS | Starting from Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months) | OS was defined as the time from the date of first dose of study drug to death due to any cause. |
| Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab | Within 24 hours before the start of the first dose of tislelizumab in Cycle 1, Day 8 of Cycle 1, and Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9, and Cycle 17 | Immunogenicity was summarized by participants who were ADA positive and developed detectable ADAs. |
| Part B: Number Of Participants Experiencing AEs | Day 1 of Cycle 1 up to 4 years and 7 months | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
| Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (0 hours and 4 hours) post dose | — |
| Part B: Maximum Observed Plasma Concentration (Cmax) Of Tislelizumab | Cycle 4 Day 1 ( 0 hours and 4 hours) post dose | As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined. |
| Part B: Ctrough Of Pamiparib | Cycle 2 Day 1 (7 hours Post-dose) | As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined. |
| Part B: Cmax Of Pamiparib | Cycle 2 (7 hours Post-dose) | As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined. |
| Part B: Percentage Of Participants With ADAs For Tislelizumab | 24 hours predose of Day 1 of every cycle | Immunogenicity was summarized by participants who developed detectable ADAs. Treatment-emergent ADAs: sum of both treatment-induced ADAs and treatment-boosted ADAs. |
| Part B: Ctrough Of Tislelizumab | Cycle 4 Day 1 ( 0 hours and 4 hours post dose) | As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined. |
| Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose) | — |
| Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib | Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose) | — |
| Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib | Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose) | — |
| Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib | Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose) | — |
| Part A: ORR | Starting from Day 1 until disease progression (up to 4 years and 7 months) | ORR was defined as the percentage of participants with a best overall response of CR and PR. |
| Part A: PFS | Starting from Day 1 until disease progression (up to 4 years and 7 months) | PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first. |
| Part A: DCR | Starting from Day 1 until disease progression (up to 4 years and 7 months) | DCR was defined as the percentage of participants with a best overall response of CR, PR, and SD. |
Countries
Australia, France, New Zealand, Spain, United Kingdom, United States
Participant flow
Recruitment details
Part A: A total of 49 participants with advanced solid tumors were enrolled in Part A of the study (dose escalation phase) at a total of 5 sites or community oncology centers in Australia. Part B: A total of 180 participants with advanced solid tumors were enrolled in Part B of the study (dose expansion phase).
Participants by arm
| Arm | Count |
|---|---|
| Part A: Dose Escalation Phase - Cohort 1 Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (20 mg twice daily) (dose escalation) until determination of the MTD/RP2D. | 12 |
| Part A: Dose Escalation Phase - Cohort 2 Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D. | 12 |
| Part A: Dose Escalation Phase - Cohort 3 Participants received tislelizumab (2 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D. | 6 |
| Part A: Dose Escalation Phase - Cohort 4 Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (40 mg twice daily) (dose escalation) until determination of the MTD/RP2D. | 13 |
| Part A: Dose Escalation Phase - Cohort 5 Participants received tislelizumab (200 mg/kg Q3W IV) with pamiparib (60 mg twice daily) (dose escalation) until determination of the MTD/RP2D. | 6 |
| Part B: Dose Expansion Phase - Arm 1a Participants with relapsed, platinum-sensitive, high-grade EOC with either known BRCA1/2 mutations or with HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. | 23 |
| Part B: Dose Expansion Phase - Arm 1b Participants with relapsed, platinum-sensitive, high-grade EOC without either known germline or somatic BRCA1/2 mutations and without known HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants must have received at least 2 prior lines of platinum-containing chemotherapy. | 23 |
| Part B: Dose Expansion Phase - Arm 2 Participants with TNBC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants could have been treated with at least 1 but no more than 3 prior lines of treatment. | 19 |
| Part B: Dose Expansion Phase - Arm 3 Participants with mCRPC with either known germline or somatic BRCA1/2 mutations or with documented HRD received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Chemotherapy-naïve participants must have received prior abiraterone acetate or enzalutamide treatment. | 20 |
| Part B: Dose Expansion Phase - Arm 4 Participants with extensive-stage disease SCLC treated with at least 1 but no more than 2 prior lines of treatment, at least 1 must have included a platinum agent, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. | 23 |
| Part B: Dose Expansion Phase - Arm 5 Participants with HER2-negative gastric or gastroesophageal junction cancer received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. Participants with HER2-negative disease could be treated with at least 1 but no more than 2 prior lines of treatment. | 20 |
| Part B: Dose Expansion Phase - Arm 6 Participants with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra, or renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a prior platinum-containing chemotherapy, received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. | 21 |
| Part B: Dose Expansion Phase - Arm 7 Participants with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more than 2 prior lines of therapy received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. At least 1 prior treatment for advanced or metastatic disease must have contained a platinum agent. Any potential participant with a known deleterious germline or somatic BRCA was eligible even if platinum naïve. | 21 |
| Part B: Dose Expansion Phase - Arm 8 Participants who were expected to benefit from the combination of a PARP inhibitor and a PD-1 inhibitor received tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This arm included participants with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix, and participants with tumors known to be MMR deficient or HRD positive) that were not eligible for inclusion in any other arms of the study. This was an exploratory signal seeking arm. | 10 |
| Total | 229 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 13 | 14 | 10 | 9 | 21 | 17 | 15 | 18 | 7 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Participant moved into special access scheme | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Participants transferred to LTE | 0 | 0 | 0 | 0 | 0 | 10 | 8 | 8 | 10 | 1 | 2 | 4 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Progressive Disease (Clinical) | 7 | 8 | 3 | 9 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease (Radiographic) | 3 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 1 | 2 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Part A: Dose Escalation Phase - Cohort 1 | Part A: Dose Escalation Phase - Cohort 2 | Part A: Dose Escalation Phase - Cohort 3 | Part A: Dose Escalation Phase - Cohort 4 | Part A: Dose Escalation Phase - Cohort 5 | Part B: Dose Expansion Phase - Arm 1a | Part B: Dose Expansion Phase - Arm 1b | Part B: Dose Expansion Phase - Arm 2 | Part B: Dose Expansion Phase - Arm 3 | Part B: Dose Expansion Phase - Arm 4 | Part B: Dose Expansion Phase - Arm 5 | Part B: Dose Expansion Phase - Arm 6 | Part B: Dose Expansion Phase - Arm 7 | Part B: Dose Expansion Phase - Arm 8 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 9.39 | 58.6 years STANDARD_DEVIATION 9.52 | 54.5 years STANDARD_DEVIATION 11.27 | 61.8 years STANDARD_DEVIATION 11.42 | 64.3 years STANDARD_DEVIATION 5.96 | 59.5 years STANDARD_DEVIATION 10.71 | 69.1 years STANDARD_DEVIATION 8.68 | 50.4 years STANDARD_DEVIATION 12.41 | 68.0 years STANDARD_DEVIATION 8.89 | 64.2 years STANDARD_DEVIATION 9.87 | 58.5 years STANDARD_DEVIATION 13.71 | 68.9 years STANDARD_DEVIATION 10.45 | 63.3 years STANDARD_DEVIATION 9.11 | 60.1 years STANDARD_DEVIATION 16.2 | 62.3 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 12 Participants | 6 Participants | 13 Participants | 6 Participants | 22 Participants | 22 Participants | 16 Participants | 18 Participants | 21 Participants | 17 Participants | 17 Participants | 19 Participants | 9 Participants | 210 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 10 Participants |
| Race (NIH/OMB) White | 10 Participants | 12 Participants | 5 Participants | 11 Participants | 6 Participants | 20 Participants | 23 Participants | 17 Participants | 18 Participants | 18 Participants | 16 Participants | 18 Participants | 19 Participants | 8 Participants | 201 Participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 5 Participants | 12 Participants | 5 Participants | 23 Participants | 23 Participants | 19 Participants | 0 Participants | 10 Participants | 3 Participants | 6 Participants | 9 Participants | 5 Participants | 140 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 20 Participants | 13 Participants | 17 Participants | 15 Participants | 12 Participants | 5 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 12 | 9 / 12 | 2 / 6 | 10 / 13 | 3 / 6 | 13 / 23 | 14 / 23 | 10 / 19 | 9 / 20 | 21 / 23 | 17 / 20 | 15 / 21 | 20 / 21 | 8 / 10 |
| other Total, other adverse events | 12 / 12 | 11 / 12 | 5 / 6 | 12 / 13 | 6 / 6 | 21 / 23 | 22 / 23 | 16 / 19 | 13 / 20 | 15 / 23 | 17 / 20 | 14 / 21 | 18 / 21 | 5 / 10 |
| serious Total, serious adverse events | 5 / 12 | 5 / 12 | 3 / 6 | 6 / 13 | 5 / 6 | 6 / 23 | 16 / 23 | 7 / 19 | 8 / 20 | 14 / 23 | 10 / 20 | 13 / 21 | 8 / 21 | 8 / 10 |
Outcome results
Primary
Part A: Number Of Participants Experiencing Adverse Events (AEs)
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: From Day 1 up to 4 years and 7 months
Population: The safety analysis set (SAF) included all participants (both parts) who received at least one dose of tislelizumab and/or pamiparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Number Of Participants Experiencing Adverse Events (AEs) | 12 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Number Of Participants Experiencing Adverse Events (AEs) | 12 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Number Of Participants Experiencing Adverse Events (AEs) | 6 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Number Of Participants Experiencing Adverse Events (AEs) | 13 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Number Of Participants Experiencing Adverse Events (AEs) | 6 Participants |
Primary
Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)
DLT was defined as an AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and occurs during the first 21 days following the first dose of tislelizumab and pamiparib in Cycle 1 and meets protocol-specified criteria. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: 21 days following the first dose of tislelizumab and pamiparib in Cycle 1
Population: SAF included all participants (both parts) who received at least one dose of tislelizumab and/or pamiparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) | 2 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) | 2 Participants |
Primary
Part B: Clinical Benefit Rate (CBR)
CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks.
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Clinical Benefit Rate (CBR) | 15 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Clinical Benefit Rate (CBR) | 7 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Clinical Benefit Rate (CBR) | 11 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Clinical Benefit Rate (CBR) | 10 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Clinical Benefit Rate (CBR) | 4 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Clinical Benefit Rate (CBR) | 4 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Clinical Benefit Rate (CBR) | 8 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Clinical Benefit Rate (CBR) | 1 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Clinical Benefit Rate (CBR) | 3 Participants |
Primary
Part B: Disease Control Rate (DCR)
DCR was defined as the percentage of participants with a best overall response of CR, PR, and stable disease (SD).
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Disease Control Rate (DCR) | 21 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Disease Control Rate (DCR) | 11 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Disease Control Rate (DCR) | 14 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Disease Control Rate (DCR) | 15 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Disease Control Rate (DCR) | 7 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Disease Control Rate (DCR) | 7 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Disease Control Rate (DCR) | 12 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Disease Control Rate (DCR) | 2 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Disease Control Rate (DCR) | 4 Participants |
Primary
Part B: Duration Of Response (DOR)
DOR, defined as the time from the first determination of an objective response, was assessed by investigator per Response Evaluation Criteria in Solid Tumors v1.1 until the first documentation of progression or death, whichever occurred first. Results are reported only for arms with responders.
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Duration Of Response (DOR) | 11.2 months |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Duration Of Response (DOR) | 6.2 months |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Duration Of Response (DOR) | 17.1 months |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Duration Of Response (DOR) | NA months |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Duration Of Response (DOR) | 6.2 months |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Duration Of Response (DOR) | NA months |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Duration Of Response (DOR) | NA months |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Duration Of Response (DOR) | NA months |
Primary
Part B: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response of complete response (CR) and partial response (PR).
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Objective Response Rate (ORR) | 7 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Objective Response Rate (ORR) | 3 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Objective Response Rate (ORR) | 9 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Objective Response Rate (ORR) | 4 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Objective Response Rate (ORR) | 2 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Objective Response Rate (ORR) | 2 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Objective Response Rate (ORR) | 6 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Objective Response Rate (ORR) | 0 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Objective Response Rate (ORR) | 3 Participants |
Primary
Part B: Overall Survival (OS)
OS was defined as the time from the date of first dose of study drug to death due to any cause.
Time frame: From Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Overall Survival (OS) | 20.9 month |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Overall Survival (OS) | 18.7 month |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Overall Survival (OS) | 15.8 month |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Overall Survival (OS) | 21.2 month |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Overall Survival (OS) | 6.9 month |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Overall Survival (OS) | 7.4 month |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Overall Survival (OS) | 8.4 month |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Overall Survival (OS) | 4.1 month |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Overall Survival (OS) | 4.1 month |
Primary
Part B: Progression-free Survival (PFS)
PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first.
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Progression-free Survival (PFS) | 8.2 month |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Progression-free Survival (PFS) | 3.5 month |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Progression-free Survival (PFS) | 8.4 month |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Progression-free Survival (PFS) | 10.4 month |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Progression-free Survival (PFS) | 2.0 month |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Progression-free Survival (PFS) | 2.1 month |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Progression-free Survival (PFS) | 3.5 month |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Progression-free Survival (PFS) | 1.9 month |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Progression-free Survival (PFS) | 2.2 month |
Secondary
Part A: CBR
CBR was defined as the percentage of participants with a best overall response of CR, PR, and SD lasting ≥ 24 weeks.
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: CBR | 2 week | Standard Deviation 16.7 |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: CBR | 5 week | Standard Deviation 41.7 |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: CBR | 4 week | Standard Deviation 66.7 |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: CBR | 4 week | Standard Deviation 30.8 |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: CBR | 4 week | Standard Deviation 66.7 |
Secondary
Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib
Time frame: Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib | 494 nanogram/milliliter | Geometric Coefficient of Variation 130 |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib | 1170 nanogram/milliliter | Geometric Coefficient of Variation 66 |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib | 1151 nanogram/milliliter | Geometric Coefficient of Variation 97 |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib | 2135 nanogram/milliliter | Geometric Coefficient of Variation 39 |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib | 2554 nanogram/milliliter | Geometric Coefficient of Variation 2.5 |
Secondary
Part A: Ctrough Of Pamiparib
Time frame: Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (Pre-dose) | 772.9 nanogram/milliliter | Geometric Coefficient of Variation 164.6 |
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (7 h) | 824.8 nanogram/milliliter | Geometric Coefficient of Variation 130.6 |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (Pre-dose) | 1258 nanogram/milliliter | Geometric Coefficient of Variation 62.13 |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (7 h) | 1469 nanogram/milliliter | Geometric Coefficient of Variation 38.14 |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (Pre-dose) | 1209 nanogram/milliliter | Geometric Coefficient of Variation 42.18 |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (7 h) | 1717 nanogram/milliliter | Geometric Coefficient of Variation 55.56 |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (7 h) | 2070 nanogram/milliliter | Geometric Coefficient of Variation 47.36 |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (Pre-dose) | 1876 nanogram/milliliter | Geometric Coefficient of Variation 60.41 |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (Pre-dose) | 2754 nanogram/milliliter | Geometric Coefficient of Variation 48.69 |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Ctrough Of Pamiparib | Cycle 2 Day 1 (7 h) | 2969 nanogram/milliliter | Geometric Coefficient of Variation 48.77 |
Secondary
Part A: DCR
DCR was defined as the percentage of participants with a best overall response of CR, PR, and SD.
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: DCR | 3 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: DCR | 6 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: DCR | 5 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: DCR | 7 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: DCR | 5 Participants |
Secondary
Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib
Time frame: Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib | 1457 nanogram/milliliter |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib | 2497 nanogram/milliliter |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib | 2985 nanogram/milliliter |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib | 2586 nanogram/milliliter |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib | 3189 nanogram/milliliter |
Secondary
Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab
Time frame: Cycle 4 Day 1 (0 hours and 4 hours) post dose
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (Pre-dose) | 23530 nanogram/milliliter | Geometric Coefficient of Variation 48.02 |
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (4 h) | 74260 nanogram/milliliter | Geometric Coefficient of Variation 20.7 |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (Pre-dose) | 26040 nanogram/milliliter | Geometric Coefficient of Variation 58.04 |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (4 h) | 66250 nanogram/milliliter | Geometric Coefficient of Variation 47.28 |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (Pre-dose) | 26160 nanogram/milliliter | Geometric Coefficient of Variation 23.69 |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (4 h) | 69020 nanogram/milliliter | Geometric Coefficient of Variation 16.47 |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (4 h) | 104300 nanogram/milliliter | Geometric Coefficient of Variation 35.31 |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (Pre-dose) | 30330 nanogram/milliliter | Geometric Coefficient of Variation 58.28 |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (Pre-dose) | 53700 nanogram/milliliter | Geometric Coefficient of Variation 81.62 |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab | Cycle 4 Day 1 (4 h) | 119600 nanogram/milliliter | Geometric Coefficient of Variation 33.83 |
Secondary
Part A: ORR
ORR was defined as the percentage of participants with a best overall response of CR and PR.
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: EFF included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: ORR | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: ORR | 3 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: ORR | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: ORR | 3 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: ORR | 3 Participants |
Secondary
Part A: OS
OS was defined as the time from the date of first dose of study drug to death due to any cause.
Time frame: Starting from Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)
Population: The efficacy evaluable set (EFF) included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: OS | 259 Days |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: OS | 413 Days |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: OS | NA Days |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: OS | 434 Days |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: OS | NA Days |
Secondary
Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab
Immunogenicity was summarized by participants who were ADA positive and developed detectable ADAs.
Time frame: Within 24 hours before the start of the first dose of tislelizumab in Cycle 1, Day 8 of Cycle 1, and Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9, and Cycle 17
Population: The Antidrug Antibody (ADA) Analysis Set included participants who received ≥ 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab | 3 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab | 0 Participants |
Secondary
Part A: PFS
PFS was defined as the time from first dose of study medication to the first documented objective disease progression or death due to any cause, whichever occurred first.
Time frame: Starting from Day 1 until disease progression (up to 4 years and 7 months)
Population: EFF included participants in the SAF who had measurable or evaluable disease at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: PFS | 64 Days |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: PFS | 77 Days |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: PFS | 190 Days |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: PFS | 107 Days |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: PFS | 373 Days |
Secondary
Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib
Time frame: Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib | 1.0 hour |
| Part A: Dose Escalation Phase - Cohort 2 | Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib | 1.1 hour |
| Part A: Dose Escalation Phase - Cohort 3 | Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib | 1.0 hour |
| Part A: Dose Escalation Phase - Cohort 4 | Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib | 1.9 hour |
| Part A: Dose Escalation Phase - Cohort 5 | Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib | 2.0 hour |
Secondary
Part B: Cmax Of Pamiparib
As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.
Time frame: Cycle 2 (7 hours Post-dose)
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab..
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Cmax Of Pamiparib | 1850 nanogram/milliliter | Geometric Coefficient of Variation 63 |
Secondary
Part B: Ctrough Of Pamiparib
As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.
Time frame: Cycle 2 Day 1 (7 hours Post-dose)
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Ctrough Of Pamiparib | 1161 nanogram/milliliter | Geometric Coefficient of Variation 80 |
Secondary
Part B: Ctrough Of Tislelizumab
As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.
Time frame: Cycle 4 Day 1 ( 0 hours and 4 hours post dose)
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Ctrough Of Tislelizumab | 46060 nanogram/milliliter | Geometric Coefficient of Variation 36 |
Secondary
Part B: Maximum Observed Plasma Concentration (Cmax) Of Tislelizumab
As pre-specified in the protocol, pharmacokinetic evaluations were performed for all Part B dose expansion arms combined.
Time frame: Cycle 4 Day 1 ( 0 hours and 4 hours) post dose
Population: The PK Analysis Set included participants in the Safety Analysis Set for whom at least one PK parameter can be derived for either pamiparib or tislelizumab.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Maximum Observed Plasma Concentration (Cmax) Of Tislelizumab | 99408 nanogram/milliliter | Geometric Coefficient of Variation 20 |
Secondary
Part B: Number Of Participants Experiencing AEs
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. All AEs reported are treatment-emergent, which was defined as having a reported onset time or worsening in severity on or after the date of the first dose of study treatment through 30 days after the last dose (permanent discontinuation of study treatment) or initiation of new anticancer therapy. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Day 1 of Cycle 1 up to 4 years and 7 months
Population: SAF will include all participants (both parts) who received at least one dose of tislelizumab and/or pamiparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Number Of Participants Experiencing AEs | 23 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Number Of Participants Experiencing AEs | 23 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Number Of Participants Experiencing AEs | 19 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Number Of Participants Experiencing AEs | 20 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Number Of Participants Experiencing AEs | 23 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Number Of Participants Experiencing AEs | 20 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Number Of Participants Experiencing AEs | 21 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Number Of Participants Experiencing AEs | 21 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Number Of Participants Experiencing AEs | 9 Participants |
Secondary
Part B: Percentage Of Participants With ADAs For Tislelizumab
Immunogenicity was summarized by participants who developed detectable ADAs. Treatment-emergent ADAs: sum of both treatment-induced ADAs and treatment-boosted ADAs.
Time frame: 24 hours predose of Day 1 of every cycle
Population: The Antidrug Antibody (ADA) Analysis Set included participants who received ≥ 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 1 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 2 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 3 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 4 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 1 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part A: Dose Escalation Phase - Cohort 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 1 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 1 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 0 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 1 Participants |
| Part B: Dose Expansion Phase - Arm 5 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 0 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 0 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 0 Participants |
| Part B: Dose Expansion Phase - Arm 6 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 0 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 0 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 0 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 0 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part B: Dose Expansion Phase - Arm 7 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 0 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Percentage Of Participants With ADAs For Tislelizumab | NAb Positive | 0 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Transient ADA Response | 2 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-emergent ADA | 2 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Persistent ADA Response | 0 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-induced ADA | 2 Participants |
| Part B: Dose Expansion Phase - Arm 8 | Part B: Percentage Of Participants With ADAs For Tislelizumab | Treatment-boosted ADA | 0 Participants |