- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04985721
A Trial of Pamiparib With Tislelizumab in Patients With Advanced Tumours With Homologous Recombination Repair Defects (IMPARP-HRD)
An Open Label, Signal Seeking, Translational, Phase II Trial of Pamiparib in Combination With Tislelizumab in Patients With Advanced Tumours With Homologous Recombination Repair Defects
Study Overview
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Stephen Luen, MBBS
- Phone Number: +61 3 8559 5000
- Email: stephen.luen@petermac.org
Study Contact Backup
- Name: Jayesh Desai, MBBS
- Phone Number: +61 8559 8339
- Email: jayesh.desai@petermac.org
Study Locations
-
-
Victoria
-
Fitzroy, Victoria, Australia, 3065
- Recruiting
- St Vincent's Hospital
-
Contact:
- Genni Newnham
-
Heidelberg, Victoria, Australia, 3084
- Recruiting
- Austin Hospital
-
Contact:
- Damien Kee
-
Melbourne, Victoria, Australia, 3000
- Recruiting
- Peter Maccallum Cancer Centre
-
Contact:
- Stephen Luen, MBBS
- Phone Number: +61 3 85595000
- Email: stephen.luen@petermac.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Have provided written informed consent
- Male or female ≥ 18 years of age
Patient has documentation of at least 1 of the following genomic features associated with HRD
Cohort A - any of:
- A germline or somatic genetic alteration that is known or suspected to be deleterious in one of the following HR-related genes (ATM, CDK12, PALB2, ARID1A, ATRX, BLM, BARD1, BRIP1, CHEK1, CHEK2, FANCA, FANCF, FANCG, FANCI, FANCL, FANCM, MSH2, NBN, RAD50, RAD51C, RAD51D, WRN)
- A somatic genetic alteration that is known or suspected to be deleterious in BRCA1 or BRCA2
- A prevalent mutational signature 3 as determined by WGS (≥ 20% of total mutations attributed)
- The presence of a positive HRD status using a NGS assay that includes assessment for genomic instability
- Cohort A excludes high grade serous ovarian cancer, TNBC, and prostate cancer
- Cohort B - a pathogenic germline BRCA1 or BRCA2 mutation Note: Genomic features associated with HRD must have been determined from a sample obtained ≤ 12 months before the date of registration into this study with the exception of germline genetic alterations which can have been determined from a sample obtained at any time.
- Patient agrees to the collection and use of their fresh tumour biopsy sample during screening for WGS Note: A fresh tumour biopsy not required for patients who have had WGS performed within 12 months prior to registration to the study
- Continues to meet all the inclusion criteria as per the TRIAGE Framework protocol
- Measurable disease, as defined by RECIST 1.1 (see Appendix 2)
Adequate haematological and end-organ function, defined by the following laboratory results obtained within 7 days prior to registration, independent of blood or platelet transfusion within 2 weeks:
- Haemoglobin ≥ 90 g/L
- ANC ≥ 1.5x109/L
- Platelet count ≥ 100 x109/L
- ALT ≤ 3.0 x the ULN, irrespective of the presence or absence of liver metastases
- AST ≤ 3.0 x the ULN, irrespective of the presence or absence of liver metastases
- Serum bilirubin ≤ 1.5 x ULN (On fractionation ≤ 90% of total bilirubin should be unconjugated.
Total bilirubin must be <4 x ULN for patients with Gilbert's Syndrome)
- Serum creatinine ≤ 1.5x ULN or eGFR ≥ 30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (appendix 5)
- INR ≤ 1.5x ULN (≤2.5x ULN if on anticoagulants)
- Patient has the ability to take oral medications without medical history of malabsorption or other chronic gastrointestinal disease, or other conditions that may harm compliance and/or absorption of the study treatment
- WOCBP must agree to use a highly effective method of birth control for the duration of the study and for 6 months after the last dose of study treatment (see Appendix 3), and have a negative serum pregnancy test within 7 days of study registration
- Non-sterile males and their female partners must agree to use a highly effective method of birth control for the duration of the study and for 6 months after the last dose of study treatment. Non- sterile males must avoid sperm donation for the duration of the study and for at least 6 months after the last study drug
- Female patient must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing biopsies, treatment, and scheduled visits and examination including follow up
Exclusion Criteria:
- One or more of the exclusion criteria as per the TRIAGE Framework protocol applies
Any previous treatment with a PARP inhibitor
Note: Prior immune checkpoint blockade is permitted provided all the criteria below are met:
- Patients must not have received the immune checkpoint blockade within 28 days of study registration
- Patients must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
All AEs while receiving prior immunotherapy must have completely resolved or resolved to grade
1 prior to screening for this study. Patients with an endocrine AE due to immunotherapy are permitted provided they are stably maintained on appropriate replacement therapy and are asymptomatic
- Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not require maintenance doses of > 10 mg prednisolone or equivalent per day
- Any unresolved toxicity (≥CTCAE grade 2) from previous anti-cancer therapy, with the exception of alopecia Note: Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the study treatment (e.g. hearing loss, peripheral neuropathy) are eligible
- Treatment with strong CYP3A inducers within 10 days (or ≤ 5 half-lives, whichever is shorter) prior to registration. Known need for treatment with strong CYP3A4 inducers during study treatment.
Symptomatic or current history of actively progressing CNS metastases. Patients with a history of treated CNS lesions are eligible, provided that all of the following criteria are met:
- Measurable disease per RECIST 1.1 must be present outside the CNS
- In patients who have received CNS-directed therapy, there is no clinical evidence of interim progression between completion of CNS-directed therapy and registration to the study (radiological re-assessment is not required)
- The patient has not received radiotherapy within 14 days prior to registration Note: Anticonvulsant therapy at a stable dose is permitted
Note: Patients with asymptomatic brain metastases in which CNS-directed therapy is not indicated are eligible
- History of leptomeningeal disease
- Mean QTc ≥ 470 ms calculated from triplicate ECGs using Fredericia's Correction
Active autoimmune disease or history of autoimmune disease that may relapse, with the following exceptions:
- Controlled type 1 diabetes
- Hypothyroidism managed with no treatment other than with hormone replacement therapy
- Controlled celiac disease
- Skin disease not requiring systemic treatment (e.g. vitiligo, psoriasis, alopecia)
- Any other disease that is not expected to recur in the absence of external triggering factors
Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 2 weeks prior to registration, with the following exceptions:
- Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
- Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
- Short course (≤ 7 days) of corticosteroid prescribed prophylactically or for the treatment of a non- autoimmune condition
- Positive HIV test at screening
- Patients with active HBV (chronic or acute; defined as having a positive HBsAg test at screening) or HCV Note: Patients with a past or resolved HBV infection (defined as the presence of HBcAb and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA
- Patients with severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including active tuberculosis and COVID-19
- Patients with a history of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc.
- History of non-viral hepatitis or cirrhosis
Any of the following cardiovascular criteria:
- Current evidence of cardiac ischemia.
- Current symptomatic pulmonary embolism.
- Acute myocardial infarction ≤ 6 months prior to study registration.
- Heart failure of New York Heart Association Classification III or IV (See Appendix 6) ≤ 6 months prior to study registration.
- Grade ≥ 2 ventricular arrhythmia ≤ 6 months prior to study registration.
- History of cerebrovascular accident within 6 months before first dose of study drugs.
- Has been administered a live vaccine within 4 weeks prior to registration
- Known sensitivity to any component of pamiparib and/or tislelizumab
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pamiparib and Tiselizumab
|
40 mg orally twice a day
200 mg IV every 21 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluation of clinical benefit rate (CBR) in patients with advanced tumours harbouring molecular profiles consistent with homologous recombination defeciency (HRD), without a known pathogenic germline BRCA1 or BRCA2 mutation.
Time Frame: 12 weeks after commencement of treatment
|
CBR, defined as the proportion of patients with either objective response (partial response (PR) + complete response (CR)) as best response, or stable disease (SD) at 12 weeks post registration, as determined by the Investigator by RECIST 1.1 in cohort A
|
12 weeks after commencement of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy of pamiparib in combination with tislelizumab in patients with advanced tumours harbouring molecular profiles consistent with HRD, and without a known pathogenic germline BRCA1 or BRCA2 mutation
Time Frame: At the end of the study, approximately 4 years after the first participant commences treatment
|
Efficacy will be measured by:
|
At the end of the study, approximately 4 years after the first participant commences treatment
|
Efficacy of pamiparib in combination with tislelizumab in patients with advanced tumours harbouring molecular profiles consistent with HRD, and without a known pathogenic germline BRCA1 or BRCA2 mutation
Time Frame: At the end of the study, approximately 4 years after the first participant commences treatment
|
Efficacy will be measured by: -progression free survival (PFS) - defined as the time from first dose of study medication to the first occurrence of disease progression, as determined by the Investigator according to RECIST 1.1, or death from any cause, whichever occurs first |
At the end of the study, approximately 4 years after the first participant commences treatment
|
Efficacy of pamiparib in combination with tislelizumab in patients with advanced tumours harbouring molecular profiles consistent with HRD, and without a known pathogenic germline BRCA1 or BRCA2 mutation
Time Frame: At the end of the study, approximately 4 years after the first participant commences treatment
|
Efficacy will be measured by: -overall survival (OS) - defined as the time from first dose of study medication to death from any cause |
At the end of the study, approximately 4 years after the first participant commences treatment
|
Evaluation of CBR of pamiparib in combination with tislelizumab in patients with advanced tumours harbouring molecular profiles consistent with HRD (independent of germline BRCA1 or BRCA2 mutation status)
Time Frame: 12 weeks post commencement of treatment
|
CBR, defined as the proportion of patients with either objective response (partial response (PR) + complete response (CR)) as best response, or stable disease (SD) at 12 weeks post registration, as determined by the Investigator by RECIST 1.1 in cohort A and B
|
12 weeks post commencement of treatment
|
Severity of Treatment -Emergent Events (Safety of pamiparib in combination with tiselizumab)
Time Frame: At the end of the study, approximately 4 years after the first participant commences treatment
|
Severity of adverse events as determined by NCI CTCAE 5.0
|
At the end of the study, approximately 4 years after the first participant commences treatment
|
Determination of HRD phenotype as a predictor of response
Time Frame: At the end of the study, approximately 4 years after the first participant commences treatment
|
A tumour based whole genome HRD assay will provide a binary outcome as to whether HRD is "present" or "absent".
Logistic regression models will be used to compare CBR between patients with tumours that have HRD "present" vs "absent".
|
At the end of the study, approximately 4 years after the first participant commences treatment
|
Collaborators and Investigators
Investigators
- Principal Investigator: Stephen Luen, MBBS, Peter MacCallum Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 20/044
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cancer
-
University of Michigan Rogel Cancer CenterRecruitingCancer Liver | Cancer Brain | Cancer Head &Neck | Cancer PelvisUnited States
-
Cellworks Group Inc.RecruitingCancer | Relapsed Cancer | Refractory CancerUnited States
-
UNC Lineberger Comprehensive Cancer CenterHyundai Hope On WheelsRecruitingCancer | Pediatric Cancer | Survivorship | Cancer MetastaticUnited States
-
Vanderbilt-Ingram Cancer CenterNational Institutes of Health (NIH)Active, not recruitingAdvanced Cancer | Relapsed Cancer | Refractory CancerUnited States
-
MiRXES Pte LtdRecruitingBreast Cancer | Gastric Cancer | Colorectal Cancer | Pancreatic Cancer | Esophageal Cancer | Ovarian Cancer | Prostate Cancer | Thoracic Cancer | Liver CancerSingapore
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedStage I Breast Cancer | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage... and other conditionsUnited States
-
Massachusetts General HospitalNational Comprehensive Cancer NetworkCompletedGastric Cancer | Pancreatic Cancer | Esophageal Cancer | Rectal Cancer | Colon Cancer | Hepatobiliary CancerUnited States
-
Johns Hopkins UniversityNational Cancer Institute (NCI); National Institute on Minority Health and...Enrolling by invitationCancer | Advanced Cancer | End Stage Cancer | MalignancyUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IV Gastric Cancer | Stage IVA Colorectal Cancer | Stage IVA Pancreatic Cancer | Stage IVB Colorectal Cancer | Stage IVB Pancreatic Cancer | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric... and other conditionsUnited States
-
Case Comprehensive Cancer CenterCompletedStage IIA Rectal Cancer | Stage IIB Rectal Cancer | Stage IIC Rectal Cancer | Stage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Stage IIIA Colon Cancer | Stage IIIB Colon Cancer | Stage IIIC Colon Cancer | Recurrent Colon Cancer | Recurrent Rectal Cancer | Stage IVA Colon Cancer | Stage IVA Rectal Cancer and other conditionsUnited States
Clinical Trials on Pamiparib
-
BeiGeneCompletedAdvanced Solid TumorsUnited Kingdom
-
Fudan UniversityRecruitingLimited Stage Small Cell Lung CancerChina
-
BeiGeneTerminatedMetastatic Castration-Resistant Prostate Cancer (mCRPC) | Homologous Recombination Deficiency (HRD)United States, Australia, Puerto Rico, Spain
-
Australia New Zealand Gynaecological Oncology GroupBeiGeneWithdrawn
-
Bai-Rong XiaRecruiting
-
BeiGeneCompletedHER2-negative Breast CancerChina
-
Sun Yat-sen UniversityRecruitingMetastatic Castration-resistant Prostate CancerChina
-
BeiGeneActive, not recruiting
-
BeiGene USA, Inc.CompletedBrain and Central Nervous System TumorsUnited States, Netherlands, Switzerland
-
BeiGeneMyriad Genetic Laboratories, Inc.CompletedSolid TumorsUnited States, Spain, United Kingdom, France, Australia, New Zealand