ANZCTR - Registration

Registration number

NCT02660034

Ethics application status

Date submitted

11/01/2016

Date registered

21/01/2016

Date last updated

6/12/2021

Titles & IDs

Public title

The Safety, Pharmacokinetics and Antitumor Activity of BGB-A317 in Combination With BGB-290 in Participants With Advanced Solid Tumors

Scientific title

A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With the PARP Inhibitor BGB-290 in Subjects With Advanced Solid Tumors

Secondary ID [1]

2017-003580-35

Secondary ID [2]

BGB-A317/BGB-290_Study_001

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Solid Tumors

Condition category

Condition code

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Other interventions - Tislelizumab
Treatment: Drugs - Pamiparib

Experimental: Part A: Dose Escalation Phase - Participants received tislelizumab and pamiparib (dose escalation) until determination of the maximum tolerated dose/recommended Phase 2 dose.

Experimental: Part B: Dose Expansion Phase - Participants received tislelizumab and pamiparib (dose expansion).

Other interventions: Tislelizumab

Treatment: Drugs: Pamiparib

Intervention code [1]

Other interventions

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part A: Number Of Participants Experiencing Adverse Events (AEs)

Timepoint [1]

From Day 1 up to 4 years and 7 months

Primary outcome [2]

Part A: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)

Timepoint [2]

21 days following the first dose of tislelizumab and pamiparib in Cycle 1

Primary outcome [3]

Part B: Objective Response Rate (ORR)

Timepoint [3]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Primary outcome [4]

Part B: Progression-free Survival (PFS)

Timepoint [4]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Primary outcome [5]

Part B: Duration Of Response (DOR)

Timepoint [5]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Primary outcome [6]

Part B: Disease Control Rate (DCR)

Timepoint [6]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Primary outcome [7]

Part B: Clinical Benefit Rate (CBR)

Timepoint [7]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Primary outcome [8]

Part B: Overall Survival (OS)

Timepoint [8]

From Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)

Secondary outcome [1]

Part A: Minimum Observed Plasma Concentration (Ctrough) Of Tislelizumab

Timepoint [1]

Cycle 4 Day 1 (0 hours and 4 hours) post dose

Secondary outcome [2]

Part A: Ctrough Of Pamiparib

Timepoint [2]

Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Secondary outcome [3]

Part A: Maximum Observed Plasma Concentration At Steady State (Cmax,ss) Of Pamiparib

Timepoint [3]

Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Secondary outcome [4]

Part A: Time To Reach Maximum Plasma Concentration At Steady State (Tmax,ss) Of Pamiparib

Timepoint [4]

Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Secondary outcome [5]

Part A: Ctrough At Steady State (Ctrough,ss) Of Pamiparib

Timepoint [5]

Cycle 2 Day 1 (Pre-dose and 7 hours Post-dose)

Secondary outcome [6]

Part A: ORR

Timepoint [6]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Secondary outcome [7]

Part A: PFS

Timepoint [7]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Secondary outcome [8]

Part A: DCR

Timepoint [8]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Secondary outcome [9]

Part A: CBR

Timepoint [9]

Starting from Day 1 until disease progression (up to 4 years and 7 months)

Secondary outcome [10]

Part A: OS

Timepoint [10]

Starting from Day 1 Every 3 months following completion or discontinuation of the treatment (up to 4 years and 7 months)

Secondary outcome [11]

Part A: Percentage Of Participants With Anti-drug Antibodies (ADAs) For Tislelizumab

Timepoint [11]

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

Secondary outcome [12]

Part B: Number Of Participants Experiencing AEs

Timepoint [12]

Day 1 of Cycle 1 up to 4 years and 7 months

Secondary outcome [13]

Part B: Ctrough Of Tislelizumab

Timepoint [13]

Cycle 4 Day 1 ( 0 hours and 4 hours post dose)

Secondary outcome [14]

Part B: Maximum Observed Plasma Concentration (Cmax) Of Tislelizumab

Timepoint [14]

Cycle 4 Day 1 ( 0 hours and 4 hours) post dose

Secondary outcome [15]

Part B: Ctrough Of Pamiparib

Timepoint [15]

Cycle 2 Day 1 (7 hours Post-dose)

Secondary outcome [16]

Part B: Cmax Of Pamiparib

Timepoint [16]

Cycle 2 (7 hours Post-dose)

Secondary outcome [17]

Part B: Percentage Of Participants With ADAs For Tislelizumab

Timepoint [17]

24 hours predose of Day 1 of every cycle

Eligibility

Key inclusion criteria

Key

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

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

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/Exclusion criteria may have applied.

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

Actual

2/02/2016

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

9/09/2020

Sample size

Target

Accrual to date

Final

229

Recruitment in Australia

Recruitment state(s)

ACT,NSW,QLD,VIC,WA

Recruitment hospital [1]

The Canberra Hospital - Garran

Recruitment hospital [2]

Mid North Coast Cancer Institute - Coffs Harbour

Recruitment hospital [3]

Calvary Mater Newcastle - Newcastle

Recruitment hospital [4]

Westmead Hospital - Parramatta

Recruitment hospital [5]

Prince of Wales - Randwick

Recruitment hospital [6]

Northern Cancer Institute - St Leonards

Recruitment hospital [7]

Icon Cancer Care - Brisbane

Recruitment hospital [8]

Monash Health - Clayton

Recruitment hospital [9]

Peter MacCallum Cancer Centre - Melbourne

Recruitment hospital [10]

Linear Clinical Research Ltd - Nedlands

Recruitment postcode(s) [1]

2605 - Garran

Recruitment postcode(s) [2]

2450 - Coffs Harbour

Recruitment postcode(s) [3]

2298 - Newcastle

Recruitment postcode(s) [4]

- Parramatta

Recruitment postcode(s) [5]

- Randwick

Recruitment postcode(s) [6]

2065 - St Leonards

Recruitment postcode(s) [7]

4101 - Brisbane

Recruitment postcode(s) [8]

- Clayton

Recruitment postcode(s) [9]

- Melbourne

Recruitment postcode(s) [10]

- Nedlands

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Arizona

Country [2]

United States of America

State/province [2]

California

Country [3]

United States of America

State/province [3]

Colorado

Country [4]

United States of America

State/province [4]

Florida

Country [5]

United States of America

State/province [5]

Massachusetts

Country [6]

United States of America

State/province [6]

New York

Country [7]

United States of America

State/province [7]

Pennsylvania

Country [8]

United States of America

State/province [8]

Tennessee

Country [9]

United States of America

State/province [9]

Texas

Country [10]

United States of America

State/province [10]

Virginia

Country [11]

France

State/province [11]

Paris

Country [12]

France

State/province [12]

Rennes

Country [13]

New Zealand

State/province [13]

Auckland

Country [14]

New Zealand

State/province [14]

Wellington

Country [15]

Spain

State/province [15]

Barcelona

Country [16]

Spain

State/province [16]

Valencia

Country [17]

United Kingdom

State/province [17]

London

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

BeiGene

Country

Other collaborator category [1]

Commercial sector/Industry

Name [1]

Myriad Genetic Laboratories, Inc.

Country [1]

Ethics approval

Ethics application status

Summary

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.

Trial website

https://clinicaltrials.gov/ct2/show/NCT02660034

Public notes

Contacts

Principal investigator

Name

Study Director

Address

BeiGene

Country

Phone

Email

Contact person for public queries

Name

Address

Country

Phone

Email

Contact person for scientific queries

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02660034