STELLAR Study

1. Cytologically or histologically confirmed solid tumor that is inoperable locally advanced, metastatic, or recurrent:

Dose-Escalation Stages (single-agent and combination therapy):

a. Subjects with a solid tumor that is unresectable or metastatic and for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective.

Cohort-Expansion Stages (single-agent and combination therapy):

The tumor cohorts for the Expansion Stages for single agent and combination therapies are as follows:

Inclusion Criterion Tumor Type Treatment

1b ccRCC XL092 (Cohort A)

1c nccRCC XL092 (Cohort B)

XL092 + Atezolizumab (Cohort E)

1d HR+ BC XL092 (Cohort C)

XL092 + Atezolizumab (Cohort F)

1e CRPC XL092 (Cohort D)

XL092 + Atezolizumab (Cohort G)

1f CRC XL092 + Atezolizumab (Cohort H: Treatment Arm H-A)

XL092 (Cohort H: Treatment Arm H-B)

1g UC (maintenance) XL092 + Avelumab (Cohort I)

1h UC (ICI-refractory) XL092 + Avelumab (Cohort J: Treatment Arm J-A)

XL092 (Cohort J: Treatment Arm J-B)

1i UC (platinum-refractory) XL092 + Avelumab (Cohort K)

ccRCC, clear cell renal cell carcinoma; HR+ BC, hormone receptor-positive breast cancer; CRC, colorectal cancer; mCRPC, metastatic castration-resistant prostate cancer; nccRCC, non-clear cell renal cell carcinoma; UC, urothelial carcinoma.

Note: Subjects enrolled into Cohort H will be randomized (1:1) to receive either XL092 + atezolizumab combination therapy (Treatment Arm H-A) or single-agent XL092 (Treatment Arm H-B). Subjects enrolled into Cohort J will be randomized (1:1) to receive either XL092 + avelumab combination therapy (Treatment Arm J-A) or single-agent XL092 (Treatment Arm J-B).Subjects in the expansion study cohorts must have received standard life-prolonging therapies or are not qualified to receive such therapies as follows:

Note: Prior investigational therapies are allowed and will count towards the maximum number of prior systemic anticancer regimens. Prior neoadjuvant/adjuvant or maintenance therapies are allowed and will not count towards the maximum allowed number of systemic anticancer regimens.

b. Cohort A (ccRCC): Subjects with previously treated advanced RCC with clear cell histology (including those with a sarcomatoid component) who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.

Allowed are a maximum of 3 prior systemic anticancer regimens for inoperable locally advanced or metastatic RCC. Examples of prior systemic therapies include VEGF-targeted therapy (eg, sunitinib, cabozantinib, axitinib, bevacizumab), immune checkpoint inhibitor (ICI) therapy (eg, pembrolizumab, nivolumab +/- ipilimumab) given either as single agents or in combination, and mTOR inhibitors (eg, everolimus).

c. Cohorts B and E (nccRCC): Subjects with previously treated advanced RCC with non-clear cell histology who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.

Allowed are a maximum of 3 prior systemic anticancer regimens for inoperable locally advanced or metastatic nccRCC. Examples of prior systemic therapies include VEGF-targeted therapy (eg, sunitinib, axitinib, bevacizumab), immune check point inhibitor (ICI) therapy for Cohort B, and mTOR inhibitors (eg, everolimus).

For Cohort E, prior immune checkpoint inhibitor (ICI) therapy is not allowed.

d. Cohorts C and F (HR+ BC): Subjects with breast cancer that is hormone receptor positive (ER+ and/or PR+) and negative for human epidermal growth factor receptor 2 (HER-2) and who have radiographically progressed during or following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease. Estrogen receptor (ER) and progesterone receptor (PR) positivity are defined as ≥ 1% of tumor cell nuclei expressing hormonal receptors via IHC analysis (ASCO/CAP Guidelines [ER and PR Testing]2020).

HER-2 negativity is defined as either of the following by local laboratory assessments (ASCO/CAP Guidelines [HER-2 Receptor Testing] 2018):

• In situ hybridization (ISH) non-amplified (ratio of HER-2 to CEP17 < 2.0 or single probe average HER-2 gene copy number < 4 signals/cell), or

• IHC 0 or IHC 1+ (if more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the Sponsor to establish eligibility of the subject).

Allowed are a maximum of 3 lines of prior systemic anticancer regimens for inoperable locally advanced or metastatic disease. Examples of prior therapies include selective estrogen receptor degraders (SERDs, eg, fulvestrant), selective estrogen receptor modulators (SERMs, eg, tamoxifen), steroidal aromatase inhibitors (SAIs, eg, exemestane), non-steroidal aromatase inhibitors (NSAIs, eg, letrozole), CDK 4/6 inhibitors (eg, palbociclib), mTOR inhibitors (eg, everolimus), PI3K inhibitors (eg, alpelisib), immune checkpoint inhibitor (ICI) therapy for Cohort C, chemotherapy.

For Cohort F, prior immune checkpoint inhibitor (ICI) therapy is not allowed.

e. Cohorts D and G (mCRPC): Subjects with metastatic CRPC (adenocarcinoma of the prostate). Neuroendocrine differentiation and other features permitted if adenocarcinoma is the primary histology.

• Subjects must have received the following prior therapies:

a. Prior taxane-based chemotherapy (eg, docetaxel or cabazitaxel) initiated for mCRPC (Note: Subjects are allowed to have received a taxane-based chemotherapy regimen for mCSPC)

b. Prior treatment with at least one novel hormonal therapy (NHT; eg, abiraterone, apalutamide, darolutamide, or enzalutamide) for castration sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (mCSPC), M0 CRPC, or mCRPC.

Allowed are a maximum of 4 prior lines of systemic anticancer regimens. Examples of additional prior systemic therapies include sipuleucel-T, radium-223, poly ADP-ribose polymerase (PARP) inhibitor, second NHT, immune checkpoint inhibitor (ICI) therapy for Cohort D, non-taxane based chemotherapy. Other hormonal therapies, such as androgen deprivation therapy (ADT) and nonsteroidal antiandrogens (NSAA), do not count toward to the total number of prior lines.

For Cohort G, prior immune checkpoint inhibitor (ICI) therapy is not allowed.

• Subjects must have castration-level testosterone < 50 ng/dL (≤ 1.73 nmol/L] following bilateral orchiectomy or by ongoing androgen-deprivation therapy (ADT)

with a gonadotropin-releasing hormone (GnRH) agonist or antagonist that must be continued throughout the study.

• Subjects must have progressive disease at study entry as defined by at least one of the following two criteria:

a. Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 or 4 consecutive assessments with an interval of at least 7 days between assessments. The most recent qualifying PSA value must be drawn within 28 days of planned enrollment. (Note: If qualifying solely by PSA progression, the screening lab PSA value must be at least 2 ng/mL [2 μg/L] but need not serve as last PSA value for determination of PSA progression; up to one PSA decrease is permitted as long as it is not the most recent value), OR

b. Radiographic soft tissue disease progression in the opinion of the Investigator.

Note: Bone disease progression alone does not qualify.

f. Cohort H (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum.

i. KRAS/NRAS wild-type, BRAF v600E wild-type

ii. Subjects with known microsatellite instability-high (MSI-H) and/or mismatch repair (MMR) deficient disease are excluded.

iii. Must have radiographically progressed during or following systemic chemotherapy that contained a fluoropyrimidine (eg, 5-fluorouracil, capecitabine) in combination with oxaliplatin or irinotecan for metastatic disease

iv. Received no more than two prior regimens for unresectable, locally advanced, recurrent, or metastatic disease

Note: Prior VEGF-targeted therapy is allowed.

g. Cohort I (UC, Maintenance Therapy): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra)

i. Stage IV disease (T4b, N0, M0; any T, N1–N3, M0; any T, any N, M1) at the start date of first-line chemotherapy

ii. Must have received at least 4 cycles but not more than 6 cycles of first-line chemotherapy of gemcitabine + cisplatin and/or gemcitabine + carboplatin. No other chemotherapy is allowed as first-line chemotherapy.

iii. Must have a disease status of an ongoing CR, PR, or SD per RECIST 1.1 as assessed by the investigator following completion of 4-6 cycles of first-line chemotherapy.

iv. The last dose of first-line chemotherapy must have been received no less than 4 weeks, and no more than 10 weeks before first dose of study treatment.

Note: Excluded are subjects with disease progression per RECIST 1.1 following first-line chemotherapy and subjects who have received prior adjuvant or neoadjuvant systemic anticancer therapy within 12 months of first dose of study treatment.

h. Cohort J (UC, ICI-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra)

i. Stage IV disease (T4b, N0, M0; any T, N1–N3, M0; any T, any N, M1)

ii. Must have progressed during or after PD-1/PD-L1 targeting immune checkpoint inhibitor therapy received as the preceding line of treatment, either as monotherapy or in combination therapy.

Note: Subjects must have received a minimum of 6 weeks of prior immune checkpoint inhibitor therapy and must not have discontinued the immune checkpoint inhibitor therapy because of intolerability.

iii. Must have received no more than 2 prior lines of systemic anticancer therapies for unresectable, locally advanced or metastatic disease.

Note: Prior ICI therapy (except with avelumab) in combination with any other immunotherapy agent, chemotherapy, or VEGF-targeted therapy is allowed.

i. Cohort K (UC, platinum-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra)

i. Stage IV disease (T4b, N0, M0; any T, N1–N3, M0; any T, any N, M1)

ii. Must have progressed during or after prior first-line platinum-based combination therapy.

Note: Prior neoadjuvant or adjuvant platinum-containing combination therapy is allowed if disease recurred < 12 months from the end of last therapy.

iii. Must have received no more than 1 prior line of systemic anticancer therapy for unresectable locally advanced or metastatic disease.

Note: Excluded are subjects who received prior PD-1/PD-L1 and/or VEGFR-targeted therapy for unresectable locally unresectable or metastatic disease.

2. Expansion Cohorts only: measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1; Eisenhauer et al 2009) as determined by the investigator.

• Inclusion requirement does not apply for Cohort I (UC, Maintenance Therapy)

Note: Measurable disease must be outside the radiation field if radiation therapy was administered. 3. Tumor tissue material:

• Subjects in the non-biomarker cohort provide archival, if available, or fresh tumor tissue if it can be safely obtained.

• Subjects in the Biomarker Cohorts provide fresh tumor and skin biopsies.

4. Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of mineralocorticosteroid).

5. Age 18 years or older on the day of consent.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.

7. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 10 days before first dose of study treatment:

a. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection.

b. Platelets ≥ 100,000/mm3 (≥ 100 GI/L)] without transfusion within 2 weeks of screening laboratory sample collection.

c. Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 2 weeks prior to screening laboratory sample collection.

d. International Normalized Ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 × upper limit of normal (ULN).

e. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 × ULN.

• For subjects with documented bone metastasis: ALP ≤ 5 × ULN. For subjects with mCRPC and bone metastasis ALP > 10 × ULN if predominantly bone-specific ALP.

f. Total bilirubin ≤ 1.5 × ULN (for subjects with Gilbert’s disease ≤ 3 × ULN).

g. For subjects in the dose-escalation cohorts, serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 60 mL/min (≥ 1.0 mL/sec) using the Cockcroft-Gault equation (see Table 14 for Cockcroft-Gault formula). For subjects in the Expansion Cohorts, serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 45 mL/min (≥ 0.75 mL/sec).

h. Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine. For subjects with RCC: ≤ 1.5 mg/mg (≤ 169.8 mg/mmol) creatinine; for subjects with UC ≤ 2 mg/mg (≤ 226.4 mg/mmol) creatinine.

8. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.

9. Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception (defined in Appendix L) during the course of the study and for 1 month after the last dose of XL092 for subjects receiving single agent therapy, for 1 month after the last dose of avelumab, or for 5 months after the last dose of atezolizumab. An additional contraceptive method, such as a barrier method (eg, condom), is required.

10. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating hormone [FSH] level > 40 mIU/mL to confirm menopause).

Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. 

1. Prior treatment with XL092 (all cohorts), prior treatment with PD-L1/PD-1 targeting immune checkpoint inhibitor (Cohorts E, F, G, H, I, and K only) or prior avelumab (Cohort J only).

2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.

3. Receipt of any type of anticancer antibody (including investigational antibody), systemic chemotherapy, or hormonal anticancer therapy (eg, antiandrogens for prostate cancer, aromatase inhibitors and selective estrogen receptor modulators for breast cancer) within 4 weeks before first dose of study treatment. Note: The antiandrogen abiraterone is permitted up to 1 week prior to first dose of study treatment. Concomitant use of megestrol acetate or leuprolide is permitted. Other types of hormonal therapies with similar use require prior Sponsor approval.

4. Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.

5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Subjects with an incidental finding of an isolated brain lesion < 1 cm in diameter may be eligible after Sponsor approval if the lesion is radiographically stable for 4 weeks before first dose and does not require treatment per Investigator judgement. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.

6. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) and platelet inhibitors (eg, clopidogrel).

Note: Allowed anticoagulants are low-dose aspirin for cardioprotection (per local applicable guidelines) and low molecular weight heparins (LMWH). Therapeutic doses of LMWH are not permitted in subjects with known brain metastases. Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.

7. Use of a strong P450 CYP3A4 inhibitor (Appendix I, Table 44) or inducer (Appendix I, Table 45) within 5 half-lives prior to first dose of study treatment.

8. Use of a sensitive substrate of CYP3A4, CYP2C19, CYP2C9, or CYP2C8 (Appendix K, Table 43) within 5 half-lives prior to first dose of study treatment.

9. Use of a sensitive substrate of P-gp or BCRP transporter (Appendix K, Table 46) within 5 half-lives prior to first dose of study treatment.

10. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

a. Cardiovascular disorders:

i. Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes).

ii. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.

iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other ischemic event or pulmonary embolism (PE) within 6 months before first dose. Upon Sponsor approval, subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with anticoagulation for at least 2 weeks before first dose.

b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:

i. Tumors invading the GI-tract from external viscera.

ii. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis

iii. Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months unless cause of obstruction is definitively managed and subject is asymptomatic.

iv. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.

Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.

v. Known gastric or esophageal varices.

c. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.

d. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.

e. Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Note: Subjects with intravascular tumor extension may be eligible following Sponsor approval.

f. Other clinically significant disorders such as:

i. Active infection requiring systemic treatment. Note: Prophylactic antibiotic treatment is allowed.

ii. Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

iii. Known positive test for or suspected infection with SARS-CoV-2 within one month before enrollment. (Note: demonstration that the subject has fully recovered from the infection is required to be eligible for enrollment).

iv. Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.

v. Malabsorption syndrome.

vi. Pharmacologically uncompensated, symptomatic hypothyroidism.

vii.Moderate to severe hepatic impairment (Child-Pugh B or C).

viii. Requirement for hemodialysis or peritoneal dialysis.

ix. History of solid organ or allogeneic stem cell transplant.

11. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose. Prior laparoscopic nephrectomy within 4 weeks prior to first dose. Minor surgery (eg, simple excision, tooth extraction) within 10 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose.

Note: Fresh tumor or skin biopsies should be performed at least 7 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible. For further information refer to Section 7.2.3.

12. Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within 10 days per electrocardiogram (ECG) before first dose of study treatment (see Section 5.6.4 for Fridericia formula).

Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility. (If triplicate ECGs cannot be performed due to logistical challenges, single ECGs are permitted; however, if the single ECG read shows QTcF > 460 ms, two additional ECGs must be performed to determine the average QTcF eligibility.)

13. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.

14. Pregnant or lactating females.

15. Inability to swallow study treatment formulation.

16. Previously identified allergy or hypersensitivity to components of the study treatment formulations.

17. Any other active malignancy or diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.

Additional for XL092 + Atezolizumab Combination Therapy Cohorts ONLY:

18. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

a. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix H for a more comprehensive list of autoimmune diseases and immune deficiencies). Subjects with the following conditions are eligible for the study:

i. A history of autoimmune-related hypothyroidism and on thyroid replacement hormone therapy

ii. Controlled Type 1 diabetes mellitus and on an insulin regimen

iii. Asthma

iv. Eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only provided all of following are true:

• Rash covers < 10% of body surface area

• Disease is well controlled at baseline and requires only low-potency topical corticosteroids

• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months

b. Known positive test for tuberculosis infection if supported by clinical or radiographic evidence of disease.

c. History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

d. Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic subjects with FT4 abnormalities can be eligible after Sponsor approval.

19. Diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior

to first dose of study treatment. Inhaled, intranasal, intraarticular, and topical corticosteroids and mineralocorticoids are allowed. Note: Adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. Transient short-term use of higher doses of systemic corticosteroids for allergic conditions (eg, contrast allergy) is also allowed.

20. Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.

For XL092 + Avelumab Combination Therapy Cohorts ONLY:

21. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions

a. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.

Note: Subjects with the following conditions are eligible for the study: Subjects with diabetes type I (controlled with an insulin regimen), vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.

22. Administration of a live, attenuated vaccine within 30 days before first dose of study treatment. 

Research Nurse: Karen Jones (x2031) Karen.Jones4@lthtr.nhs.uk