Locally Advanced or Metastatic Solid TumorsPhase 1NCT03150810
Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors
A Phase 1 study testing Pamiparib and Temozolomide in people with Locally Advanced or Metastatic Solid Tumors, run by BeiGene at 22 sites in 4 countries.
Trial summary
The primary objective of this study was to determine the safety and tolerability of pamiparib, the maximum tolerated dose (MTD) or maximum administered dose (MAD) for pamiparib combined with TMZ, to select the recommended Phase 2 dose (RP2D) and schedule of pamiparib in combination with TMZ, and to determine the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced or Metastatic Solid Tumors
- What is being tested?
- Pamiparib and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 22 sitesin 4 countries
- Study dates
- 28 Jun 2017to 4 May 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years old with advanced or metastatic stage solid tumors
- Eastern Cooperative Oncology Group (ECOG) status ≤ 1
- Have disease either evaluable (dose-escalation cohort) or measurable (dose-escalation and -expansion cohorts) per RECIST V1.1, except for prostate cancer participants
- Agree to provide archival tumor tissue
- Additional inclusion criteria for dose expansion cohorts:
- Participants with homologous recombination deficiency (HRD+) or known BRCA mutant ovarian cancer Previously received at least one line of platinum-containing therapy in the advanced or metastatic setting and No progression or recurrent disease within 6 months from last platinum-containing regimen.
Show all 10Show fewer
- Participants with HRD+ or known BRCA mutant triple-negative breast cancer Up to one prior platinum-containing treatment in any treatment setting and up to 3 prior lines of therapy in the advanced or metastatic setting
- Participants with HRD+ or known BRCA mutant prostate cancer Chemotherapy-naïve or previously received up to two taxane-based chemotherapy regimens, with documented prostate cancer progression
- Participants with small cell lung cancer and gastric cancer, previously received ≤ 2 prior lines of therapy
- Other HRD+ solid tumors of multiple indications
Who cannot join
- Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.
- Refractory to platinum-based therapy (dose-expansion cohort).
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
22 sites in 4 countries.
22 sites in 4 countries
United States7 sites
Texas Oncology (Loop) Usor
Dallas, Texas, 75230
Start Midwest
Grand Rapids, Michigan, 49503
The University of Texas Md Anderson Cancer Center
Houston, Texas, 77030-4009
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
Mount Sinai Prime
New York, New York, 10029
Washington University in St Louis
St Louis, Missouri, 63110
Montefiore Medical Park At Eastchester Einstein Campus
The Bronx, New York, 10467
Spain7 sites
Hospital Universitario Vall Dhebron
Barcelona, 08035
Ico H Duran I Reynals
Barcelona, 08907
Hospital Universitario Ramon Y Cajal
Madrid, 28034
Start Madrid Fundacion Jimenez Diaz
Madrid, 28040
Centro Integral Oncologico Clara Campal
Madrid, 28050
Hospital Universitario Virgen de La Macarena
Seville, 41009
Hospital Clinico Universitario de Valencia
Valencia, 46010
Australia4 sites
Chris Obrien Lifehouse
Camperdown, New South Wales, 2050
Saint Vincents Hospital Sydney
Darlinghurst, New South Wales, 2010
Peter Maccallum Cancer Centre
Melbourne, Victoria, 3000
Icon Cancer Centre South Brisbane
South Brisbane, Queensland, 4101
United Kingdom4 sites
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Northern Centre For Cancer Care
High Heaton, NE7 7DN
University College Hospital
London, NW1 2PG
Sarah Cannon Research Institute Uk
London, W1G 6AD
About this study
Official title: A Phase 1b Study to Assess the Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Subjects With Locally Advanced or Metastatic Solid Tumors
The primary objective of this study was to determine the safety and tolerability of pamiparib, the maximum tolerated dose (MTD) or maximum administered dose (MAD) for pamiparib combined with TMZ, to select the recommended Phase 2 dose (RP2D) and schedule of pamiparib in combination with TMZ, and to determine the antitumor activity of pamiparib in combination with TMZ.
- Being tested
- Pamiparib, Temozolomide
- Keywords
- Ovarian cancer, Triple negative breast cancer, Small cell lung cancer, Gastric cancer, temozolomide, BGB-290, antineoplastic agents, alkylating, alkylating agents,, Poly (ADP-ribose) polymerase inhibitors, enzyme inhibitors, Head and neck cancer, Esophageal cancer, Soft tissue sarcoma, Non small cell lung cancer, pamiparib
- Medical subject headings
- Ovarian Neoplasms, Triple Negative Breast Neoplasms, Small Cell Lung Carcinoma, Stomach Neoplasms, Head and Neck Neoplasms, Esophageal Neoplasms, Sarcoma, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PamiparibDrug
Also called BGB-290
Administered by mouth as a capsule twice daily
TemozolomideDrug
Also called TMZ, temodar
TMZ at various doses administered by mouth as a capsule once daily.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7) | Experimental | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7) | Experimental | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7) | Experimental | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7) | Experimental | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7) | Experimental | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 120 mg once daily on Days 1 to 7 within a 28-day cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14) | Experimental | Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 14 within a 28-day cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28) | Experimental | Pamiparib 60 mg twice daily in combination with TMZ 20 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28) | Experimental | Pamiparib 60 mg twice daily in combination with TMZ 40 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Expansion: Gastric Cancer | Experimental | Participants with gastric or gastroesophageal junction cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Expansion: Ovarian Cancer | Experimental | Participants with ovarian cancer, fallopian cancer, or primary peritoneal cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Expansion: SCLC | Experimental | Participants with Small Cell Lung Cancer (SCLC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Expansion: TNBC | Experimental | Participants with triple negative breast cancer (TNBC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
| Dose Expansion: Other HRD+ Cancers | Experimental | Participants with non-small cell lung cancer (NSCLC), esophageal cancer, squamous head and neck cancer, or soft tissue sarcomas whose tumors are homologous recombination deficiency (HRD)+ received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle Receives: Drug: Pamiparib; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT is defined as one of the following toxicities occurring during the DLT assessment window:
Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting >7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting > 3 days and requiring transfusion, or any decreased platelet count <15,000/mm3/ <15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)
Measured: From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)
Number of Participants Experiencing Adverse Events (AEs)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.03
Measured: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 5 years and 10 months
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where BOR is defined as the best response recorded from the first postbaseline tumor assessment until data cutoff date, disease progression or start of new anticancer treatment.
Measured: Up to approximately 5 years and 10 months
Secondary outcomes (13)
Maximum Observed Plasma Concentration (Cmax) of Pamiparib
Pamiparib pharmakokinetic (PK) parameters were assessed in the first 20 participants enrolled in the dose escalation phase after a single dose on Day -2 and at steady state in combination with TMZ on Day 15.
Measured: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose (each cycle is 28 days)
Plasma Trough Concentrations of Pamiparib (Ctrough)
Measured: Cycle 1 Day 15 predose
Time to Reach Cmax (Tmax) of Pamiparib
Measured: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.
Area Under the Curve From Time 0 to 4 Hours (AUC0-4h) of Pamiparib
Measured: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, and 4 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Pamiparib
Measured: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing
Terminal Elimination Half-life (t1/2) of Pamiparib
Measured: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
Apparent Clearance (CL/F) of Pamiparib
Measured: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Pamiparib
Measured: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
Plasma Concentration of Temozolomide (TMZ)
Measured: Predose (within 30 min prior to dose) and 1 hour post dose on Cycle 1 Day 1 and Cycle 1 Day 7
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD) based on investigator assessment using RECIST v1.1.
Measured: Up to approximately 5 years and 10 months
Duration of Response (DOR)
DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to disease progression or death due to any cause, whichever occurs earlier, based on investigator assessment using RECIST v1.1. Only responders will be included in the assessment.
Measured: Up to approximately 5 years and 10 months
Progression Free Survival (PFS)
PFS is defined as the time (months) from the date of the first dose of combination treatment to disease progression or death due to any cause, whichever occurs first, based on investigator assessment using RECIST v1.1
Measured: Up to approximately 5 years and 10 months)
Overall Survival (OS)
OS is defined as the time from the date of the first dose of combination treatment to death due to any cause.
Measured: Up to approximately 5 years and 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start28 Jun 2017
- Primary completion4 May 2023
- Study completion4 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
- More trials run by BeiGeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Myriad Genetics, Inc.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03150810
- Sponsor's protocol ID
- BGB-290-103
- Other IDs
- 2017-001553-14, 2017
- Status last verified
- Dec 2024
- First submitted
- 8 May 2017
- Last updated
- 20 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Stradella A, Johnson M, Goel S, Park H, Lakhani N, Arkenau HT, Galsky MD, Calvo E, Baz V, Moreno V, Saavedra O, Luen SJ, Mu S, Wan Q, Chang V, Zhang W, Barve M. Phase 1b study to assess the safety, tolerability, and clinical activity of pamiparib in combination with temozolomide in patients with locally advanced or metastatic solid tumors. Cancer Med. 2024 Jul;13(13):e7385. doi: 10.1002/cam4.7385.
PubMed 38970256
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study to Assess the Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Subjects With Locally Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT03150810
- Acronym / sponsor ID
- BGB-290-103
- Keywords
- Ovarian cancer, Triple negative breast cancer, Small cell lung cancer, Gastric cancer, temozolomide, BGB-290, antineoplastic agents, alkylating, alkylating agents,
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 139 participants (actual)
- Lead sponsor
- BeiGeneIndustry (pharma, biotech, devices)
- Collaborators
- Myriad Genetics, Inc.
- Study start
- 28 Jun 2017 (actual)
- Primary completion
- 4 May 2023 (actual)
- Study completion
- 4 May 2023 (actual)
- First posted
- 12 May 2017 (actual)
- Results
- Posted 20 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study was to determine the safety and tolerability of pamiparib, the maximum tolerated dose (MTD) or maximum administered dose (MAD) for pamiparib combined with TMZ, to select the recommended Phase 2 dose (RP2D) and schedule of pamiparib in combination with TMZ, and to determine the antitumor activity of pamiparib in combination with TMZ.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7) | Experimental | Drug: Pamiparib, Drug: TemozolomidePamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7) | Experimental | Drug: Pamiparib, Drug: TemozolomidePamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7) | Experimental | Drug: Pamiparib, Drug: TemozolomidePamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7) | Experimental | Drug: Pamiparib, Drug: TemozolomidePamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7) | Experimental | Drug: Pamiparib, Drug: TemozolomidePamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 120 mg once daily on Days 1 to 7 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14) | Experimental | Drug: Pamiparib, Drug: TemozolomidePamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 14 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28) | Experimental | Drug: Pamiparib, Drug: TemozolomidePamiparib 60 mg twice daily in combination with TMZ 20 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle |
| Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28) | Experimental | Drug: Pamiparib, Drug: TemozolomidePamiparib 60 mg twice daily in combination with TMZ 40 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle |
| Dose Expansion: Gastric Cancer | Experimental | Drug: Pamiparib, Drug: TemozolomideParticipants with gastric or gastroesophageal junction cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Dose Expansion: Ovarian Cancer | Experimental | Drug: Pamiparib, Drug: TemozolomideParticipants with ovarian cancer, fallopian cancer, or primary peritoneal cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Dose Expansion: SCLC | Experimental | Drug: Pamiparib, Drug: TemozolomideParticipants with Small Cell Lung Cancer (SCLC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Dose Expansion: TNBC | Experimental | Drug: Pamiparib, Drug: TemozolomideParticipants with triple negative breast cancer (TNBC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
| Dose Expansion: Other HRD+ Cancers | Experimental | Drug: Pamiparib, Drug: TemozolomideParticipants with non-small cell lung cancer (NSCLC), esophageal cancer, squamous head and neck cancer, or soft tissue sarcomas whose tumors are homologous recombination deficiency (HRD)+ received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥18 years old with advanced or metastatic stage solid tumors
- Eastern Cooperative Oncology Group (ECOG) status ≤ 1
- Have disease either evaluable (dose-escalation cohort) or measurable (dose-escalation and -expansion cohorts) per RECIST V1.1, except for prostate cancer participants
- Agree to provide archival tumor tissue
- Additional inclusion criteria for dose expansion cohorts:
Key exclusion criteria (3 listed)
- Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.
- Refractory to platinum-based therapy (dose-expansion cohort).
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PamiparibAlso: BGB-290Administered by mouth as a capsule twice daily | Drug | Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7), Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7), Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28), Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14), Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28), Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7), Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7), Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7), Dose Expansion: Gastric Cancer, Dose Expansion: Other HRD+ Cancers, Dose Expansion: Ovarian Cancer, Dose Expansion: SCLC, Dose Expansion: TNBC |
| TemozolomideAlso: TMZ, temodarTMZ at various doses administered by mouth as a capsule once daily. | Drug | Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7), Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7), Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28), Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14), Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28), Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7), Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7), Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7), Dose Expansion: Gastric Cancer, Dose Expansion: Other HRD+ Cancers, Dose Expansion: Ovarian Cancer, Dose Expansion: SCLC, Dose Expansion: TNBC |
Primary outcome
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)
A DLT is defined as one of the following toxicities occurring during the DLT assessment window: Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting >7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting > 3 days and requiring transfusion, or any decreased platelet count <15,000/mm3/ <15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)
Number of Participants Experiencing Adverse Events (AEs)
Time frame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 5 years and 10 months
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.03
Objective Response Rate (ORR)
Time frame: Up to approximately 5 years and 10 months
ORR is defined as the percentage of participants who have a best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where BOR is defined as the best response recorded from the first postbaseline tumor assessment until data cutoff date, disease progression or start of new anticancer treatment.
13 secondary outcomes
Maximum Observed Plasma Concentration (Cmax) of Pamiparib
Time frame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose (each cycle is 28 days)
Plasma Trough Concentrations of Pamiparib (Ctrough)
Time frame: Cycle 1 Day 15 predose
Time to Reach Cmax (Tmax) of Pamiparib
Time frame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.
Area Under the Curve From Time 0 to 4 Hours (AUC0-4h) of Pamiparib
Time frame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, and 4 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Pamiparib
Time frame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing
Terminal Elimination Half-life (t1/2) of Pamiparib
Time frame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
Apparent Clearance (CL/F) of Pamiparib
Time frame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Pamiparib
Time frame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
Plasma Concentration of Temozolomide (TMZ)
Time frame: Predose (within 30 min prior to dose) and 1 hour post dose on Cycle 1 Day 1 and Cycle 1 Day 7
Disease Control Rate (DCR)
Time frame: Up to approximately 5 years and 10 months
Duration of Response (DOR)
Time frame: Up to approximately 5 years and 10 months
Progression Free Survival (PFS)
Time frame: Up to approximately 5 years and 10 months)
Overall Survival (OS)
Time frame: Up to approximately 5 years and 10 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38970256Stradella A, Johnson M, Goel S, Park H, Lakhani N, Arkenau HT, Galsky MD, Calvo E, Baz V, Moreno V, Saavedra O, Luen SJ, Mu S, Wan Q, Chang V, Zhang W, Barve M. Phase 1b study to assess the safety, tolerability, and clinical activity of pamiparib in combination with temozolomide in patients with locally advanced or metastatic solid tumors. Cancer Med. 2024 Jul;13(13):e7385. doi: 10.1002/cam4.7385.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
BeiGene
22 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pamiparib and Temozolomide in people with Locally Advanced or Metastatic Solid Tumors, run by BeiGene at 22 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Spain, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03150810, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.