Clinical trial NCT02361723: Phase 1a/1b BGB-290 for Advanced Solid Tumors.
Official title: A Phase 1A/1B, Open Label, Multiple Dose, Dose Escalation, and Expansion Study to Investigate the Safety, Pharmacokinetics, Food Effect, and Antitumor Activities of BGB-290 in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: For Participants With Advanced Solid Tumors Failed With Previous Lines of Treatment
Keywords: Advanced Solid Tumors
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2015-02-12
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study contains Phase 1A and Phase 1B. Phase 1A has Part1 (BID Dose Escalation) and Part2 (QD Dosing Escalation) Evaluation of a cohort of at least three participants completing one cycle of treatment at that dose level and dose regimen is required prior to determining the next dose level and dose regimen for the next cohort. Phase 1B has PartA (BID Dosing Expansion) will investigate efficacy in participants with selected tumor types and further evaluate safety and tolerability of BGB 290 at recommended dose for future studies. and PartB (Food Effect) will investigate the food effect on the Pharmacokinetics (PK) of BGB 290 in participants with advanced solid tumors.

Detailed description: The study contains Phase 1A and Phase 1B. Phase 1A has Part1 (BID Dose Escalation) and Part2 (QD Dosing Escalation) Evaluation of a cohort of at least three participants completing one cycle of treatment at that dose level and dose regimen is required prior to determining the next dose level and dose regimen for the next cohort. Phase 1B has PartA (BID Dosing Expansion) will investigate efficacy in participants with selected tumor types and further evaluate safety and tolerability of BGB 290 at recommended dose for future studies. and PartB (Food Effect) will investigate the food effect on the PK of BGB 290 in participants with advanced solid tumors.

Eligibility criteria: Key Inclusion Criteria:

1. Male or female and at least 18 years of age with a life expectancy of at least 12 weeks.
2. Histologically or cytologically confirmed malignancy that has progressed to the advanced or metastatic stage for which no effective standard therapy is available.
3. BRCA1/2 mutations are not required but enrichment of this participant population is permitted.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
5. Adequate bone marrow, liver, and renal function.
6. Participants who have histologic or cytologic confirmation of malignancy that has progressed to the advanced or metastatic stage.
7. Eligible participants who have received the prior chemotherapy regimen in the advanced or metastatic setting.
8. Females of childbearing potential unwilling to use a highly effective method of contraception during treatment and throughout the study until 28 days after the last investigational product administration.
9. Able to swallow and retain oral medication.

Key Exclusion Criteria:

1. Participants did not receive prior therapies targeting poly-ADP ribose polymerase (PARP).
2. Participants who are not considered to be refractory to platinum-based therapy (e.g., progressive disease at the first tumor assessment while receiving platinum treatment).
3. Participants who have not been treated with chemotherapy, biologic therapy, immunotherapy, or other investigational agent within five times half-lives of the last treatment or within 4 weeks (whichever is longer) prior to starting study drug (or who have not recovered from the side effects of such therapy).
4. Participants who have not undergone major surgery/surgical therapy for any cause within 4 weeks of screening visit.
5. Participants must have recovered from the treatment and have a stable clinical condition before entering this study.
6. Participants who have not received therapeutic radiotherapy to target lesions. 7.Participants who have received local palliative radiotherapy of non-target lesions for local symptom control within the last 21 days must have recovered from any adverse effects of radiotherapy before recording screening symptoms. 8.No untreated brain metastasis or unstable neurologic condition after the completion of radiation, or requiring corticosteroid of \> 40 mg prednisone daily equivalent dose to control the symptoms.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Objective response rate ([ORR]: Complete Response (CR) + Partial Response (PR)) based on RECIST Version 1.1
timeFrame: through study completion, an average of 1 year
measure: Prostate-specific antigen (PSA) response (for prostate cancer participants only) based on Prostate Cancer Working Group 2 (PCWG2) criteria
timeFrame: through study completion, an average of 1 year
measure: Primary PK 1
timeFrame: through study completion, an average of 1 year
measure: Primary PK 2
timeFrame: through study completion, an average of 1 year
measure: Primary PK 3
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Progression free survival
timeFrame: through study completion, an average of 1 year
measure: Duration of response for responders (CR or PR) and duration of SD (defined only for participants whose confirmed best response is CR, PR, or SD.
timeFrame: through study completion, an average of 1 year
measure: The number and proportion of participants who achieve objective tumor response (complete response [CR], partial response [PR], and CR+PR) or stable disease (SD).
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Cancer Care Wollongong
state: New South Wales
city: Bedford PK
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
affiliation: Linear Clinical Research
name: Michael Millward, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lickliter JD, Gan HK, Meniawy T, Yang J, Wang L, Luo LS, Millward M. A phase I dose-escalation study of BGB-290, a novel PARP1/2 selective inhibitor in patients with advanced solid tumors. Journal of Clinical Oncology. 2016; 34(15): DOI: 10.1200/JCO.2016.34.15_suppl.e17049
citation: Lickliter JD, Voskoboynik M, Mileshkin L, Gan HK, Kichenadasse G, Zhang K, Zhang M, Tang Z, Millward M. Phase 1A/1B dose-escalation and -expansion study to evaluate the safety, pharmacokinetics, food effects and antitumor activity of pamiparib in advanced solid tumours. Br J Cancer. 2022 Mar;126(4):576-585. doi: 10.1038/s41416-021-01632-2. Epub 2021 Nov 18.
citation: Xu B, Yin Y, Dong M, Song Y, Li W, Huang X, Wang T, He J, Mu X, Li L, Mu S, Zhang W, Li M. Pamiparib dose escalation in Chinese patients with non-mucinous high-grade ovarian cancer or advanced triple-negative breast cancer. Cancer Med. 2021 Jan;10(1):109-118. doi: 10.1002/cam4.3575. Epub 2020 Oct 31.