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

Inclusion Criteria:

1. Patients have voluntarily agreed to participate by giving written informed consent.

2. Patients must have received standard of care in the primary treatment of their
disease.

3. Patients who have the below specified histologically confirmed malignancies that have
progressed to the advanced or metastatic stage.

1. In Part A, the patients must have an advanced malignancy including but not
limited to high-grade serous cancer of the ovary, fallopian tube, or peritoneum,
triple negative breast 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 patients recruited to one of the eight expansion arms must have
advanced solid tumors of the following types:

Arm 1: Patients with relapsed, platinum-sensitive high grade epithelial, non-mucinous,
ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) must meet the
following criteria:

i. Patients must have at least 2 prior platinum-containing treatments in any treatment
setting.

• Note: patients may have received additional therapy after the last
platinum-containing regimen if the other eligibility criteria are met.

ii. Patients must have platinum-sensitive recurrent disease and must not have
progressed (by RECIST v1.1 criteria) within 6 months of the completion of the last
platinum containing line of treatment

• Note: patients may receive additional non-platinum based chemotherapy for recurrence
after prior last platinum containing regimen if the criteria for platinum sensitivity
are met.

iii. Arm 1a: Patients with relapsed, platinum-sensitive high grade epithelial,
non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) with
either known deleterious or suspected deleterious germline or somatic BRCA1/2
mutations or with HRD

• If HRD or BRCA1/2 mutation status from archival tissue is unknown or has not been
previously evaluated, then the archival tissue must undergo tissue screening using a
validated diagnostic test to determine eligibility. If the diagnostic test result is
BRCA1/2 or HRD positive the patient will be eligible for enrollment in Arm 1a iv. Arm
1b: Patients with relapsed, platinum-sensitive high grade EOC who otherwise meet the
above criteria and are without known germline or somatic BRCA1/2 mutations and without
HRD mutation

Arm 2: Patients with triple negative breast cancer must meet the following criteria:

i. Patients with 0-1 prior platinum-containing treatment in any treatment setting

• Note: patients could have received additional therapy after the last
platinum-containing line of treatment if the other eligibility criteria are met.

ii. Patients who have 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 is unknown or has not been
previously evaluated, then the archival tissue must undergo tissue screening
using a validated diagnostic test to determine eligibility. If the diagnostic
test result is HRD positive, then the patient will be eligible for enrollment in
Arm 2

- If archival tissue is not available and the patient submits a fresh tumor biopsy,
then the diagnostic test needs to demonstrate somatic BRCA1/2 mutation or HRD
positivity.

Arm 3: Patients 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 meet the following criteria:

i. The patient 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 is used more than once, this will be 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 do not need to be
checked if the patient has undergone surgical castration for > 4 months. Patients
receiving chemical castration should have 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 (LHRH) antagonist/agonist is to
be continued in these patients

- Patients with only non-measurable bone lesions must have disease progression
based on PCWG3 with 2 or more new lesions or have prostate-specific antigen (PSA)
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 is unknown or has not been
previously evaluated, then the archival tissue must undergo tissue screening
using a validated diagnostic test to determine eligibility. If the diagnostic
test result is HRD positive, then the patient will be eligible for enrollment in
Arm 3

- If archival tissue is not available and the patient submits a fresh tumor biopsy,
then the diagnostic test needs to demonstrate somatic BRCA1/2 mutation or HRD
positivity.

Arm 4: Patients with extensive-stage disease small cell lung cancer (SCLC) must meet
the following criterion:

i. Patients 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: Patients with HER2-negative gastric or gastroesophageal junction cancer must
meet the following criteria:

i. Patients with HER2-negative may have received at least 1 and not more than 2 prior
lines of treatment

Arm 6: Patients with locally advanced or metastatic urothelial (muscle-invasive
bladder, ureter, urethra or renal pelvis) cancer must meet the following criteria:

i. Patients 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: Patients with advanced or metastatic pancreatic adenocarcinoma must meet the
following criteria:

i. Received at least one 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. Patients with known deleterious
germline or somatic BRCA1/2 mutation can be considered for the study even if
platinum-naive

Arm 8: (NOTE: CLOSED TO ENROLLMENT) Patients with advanced or metastatic recurrent
non-ovarian gynecological cancers (endometrial cancer, cancer of the cervix and
patients with tumors known to be MMR deficient or HRD positive) must meet the
following criteria:

i. Patients 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 will approve tumor types for Arm 8 prior to screening

• Note: Excluded tumor types include patients with bone or soft tissue sarcoma;
central nervous system (CNS) malignancies; colorectal cancer (except microsatellite
instability-high [MSI H] 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. Patients who were treated with chemotherapy or any investigational therapies, if
eligible, must have been 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 AEs have either returned to baseline or

5. At least 2 weeks from palliative radiotherapy

6. Patients must have 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 are recommended at baseline in patients with readily
accessible tumor lesions and who consent to the biopsies). Patients with ovarian,
fallopian tube, primary peritoneal, or breast cancer in Part A and all patients
enrolled in Part B must also agree to provide fresh blood sample at the baseline for
the evaluation of BRCA mutations and/or confirmation of prior BRCA results or other
homologous recombination deficiency mutations even if it was previously tested

7. Patients must have measurable disease as defined in RECIST v1.1. Patients with
metastatic castration-resistant prostate cancer and epithelial, non-mucinous, ovarian
cancer, fallopian tube, or primary peritoneal cancer may use separate disease-specific
criteria

8. Patients must be a male or female ≥ 18 years of age on the day of signing informed
consent

9. Patients must have an ECOG Performance Status (PS) ≤ 1

10. Patients must have a life expectancy ≥ 12 weeks

11. Patient must have adequate organ function

12. Females of childbearing potential must be 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 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 be 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 avoid sperm donation for
the duration of the study and for at least 6 months after last study drug

14. 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

Exclusion criteria:

1. Platinum-resistant/refractory disease, defined as progressive disease at the first
tumor assessment while receiving platinum-containing chemotherapy

2. Patient has history of severe hypersensitivity reactions to other monoclonal
antibodies (mAbs).

3. Any major surgery within 28 days before first dose of study drugs.

4. Prior allogeneic stem cell transplantation or organ transplantation.

5. Patients with toxicities (as a result of prior anticancer therapy) which have not
recovered to baseline or stabilized, except for AEs not considered a likely safety
risk (eg, alopecia, neuropathy and specific laboratory abnormalities).

6. Concurrent participation in another therapeutic clinical trial.

7. Prior malignancy within the previous 2 years except for locally curable non-melanoma
dermatologic cancers that have 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 MRI of the brain
and spinal cord is required for SCLC patients enrolled in Arm 4 if they have a history
of CNS disease.

Note: Patients with previously treated CNS metastatic disease are eligible for any arm
if CNS metastatic disease is asymptomatic, clinically stable, and does 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. The
exception to this criterion are patients eligible for Arm 9; where patients may have
received either a PD-1 inhibitor or PD-L1 inhibitor.

10. Active autoimmune diseases or history of autoimmune diseases that may relapse.

Note: Patients with the following diseases are not excluded and may proceed 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 (eg, vitiligo, psoriasis,
alopecia).

5. Any other disease that is 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: Patients who are currently or have previously been on any of the following
steroid regimens are 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 (eg, for
contrast dye allergy) or for the treatment of a non-autoimmune condition (eg,
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, etc.

13. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled
systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung
diseases, etc.

14. History of non-viral hepatitis or cirrhosis.

15. Positive human immunodeficiency virus (HIV) status.

16. A known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

17. History of alcohol abuse.

18. Underlying medical conditions or alcohol or drug abuse or dependence that, in the
investigator's opinion, will be unfavorable for the administration of study drug or
affect the explanation of drug toxicity or adverse events; 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. Patients
should not have gastrointestinal illnesses that would preclude the absorption of
pamiparib, which is an oral agent.

20. Has 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 have 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