Combination of SON-1010 (IL12-FHAB) and Atezolizumab in Patients With Platinum-resistant Ovarian Cancer

Inclusion Criteria:

1. Age ≥18 years at the time of informed consent

2. Part 1: Must have histologically or cytologically verified solid tumors and patientsmust have locally advanced or metastatic disease. Must have been treated withstandard of care therapies for their disease and have no standard alternativetreatment options that are deemed by the treating physician to offer reasonable orpotentially better benefit. Patients in cohorts C4, C5, and the RP2D expansion groupmust have PROC. Part 2: Must have PROC, defined as recurrence of OC within 6-months (180-days) afterthe last dose of a platinum-containing regimen), including epithelial, fallopiantube, or 1° peritoneal carcinoma. Patients may have had one or more alternativeregimen(s) before this trial, including maintenance therapy between consecutivelines of therapy. Evidence of progression and the timing of progression orreoccurrence must refer to new measurable disease by RECIST v1.1 or evaluable (non-measurable) disease. The latter is defined as not having measurable disease buthas pre-study baseline values of CA125 at least 2 x ULN, with ascites and/or pleuraleffusion attributed to tumor OR with solid and/or cystic abnormalities onradiographic imaging consistent with recurrent disease that do not meet RECIST 1.1definitions for target lesions.

3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

4. Adequate organ and bone marrow function, in the absence of growth factors.

5. Females of childbearing potential, or < 1-year postmenopause who are not permanentlysterile, must have a negative serum pregnancy test (beta-human chorionicgonadotropin [β-HCG]) at baseline, and agree to use 2 highly effective methods ofbirth control during the study and for 30 days after the last dose of study drug.Females who are not of childbearing potential (have had a tubal ligation,hysterectomy, or bilateral oophorectomy, or are ≥ 1-year postmenopause) or have apartner who has had a vasectomy do not need to use contraception. A folliclestimulating hormone (FSH) level > 35 IU/L at screening will be performed to confirmstatus. Refer to Section 8.2.7 for further detail.

6. Males and their female partners must use a highly effective method of birth controlif female partner(s) is of childbearing potential and must not donate sperm duringthe study and for 90 days after the last dose of study drug.

7. Willing and able to provide signed informed consent, which includes compliance withthe requirements and restrictions listed in the informed consent form (ICF) and inthis protocol.

Exclusion Criteria:

1. Known history of allergy to any component of study drug or a history of severeallergic/anaphylactic reaction.

2. Hospitalization for subacute bowel obstruction, other complications of the cancer,or any major surgery within 28 days prior to C1D1. Elective surgery is allowed ifrecovered.

3. Infection with HIV-1 or HIV-2 or a history of Kaposi sarcoma and/or MulticentricCastleman Disease.

4. Current active liver disease from any cause, including hepatitis A (hepatitis Avirus IgM positive), hepatitis B (hepatitis B virus [HBV] surface antigen positive),or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCVribonucleic acid). Patients with HCV with undetectable virus after treatment areeligible (note: patients must have completed curative anti-viral therapy at least 4weeks prior to screening). Patients with a prior history of HBV are eligible ifquantitative PCR for HBV DNA is negative (note: patients must have received HBVantiviral therapy for at least 4 weeks prior to screening)

5. Pregnancy and/or lactation

6. Has received a live or live-attenuated vaccine within 30 days prior to the firstdose of study drug. (Note: Administration of killed vaccines and COVID-19 vaccinesthat are not live or live-attenuated are allowed if > 14 days.)

7. History of any active infection requiring systemic antibiotics, antivirals orantifungals, including COVID-19, within 14 days before the first dose of study drug.

8. Any acute noninfectious illness not resolved by14 days before day 1.

9. History of or known or suspected autoimmune disease (exception(s): patients withvitiligo, Type I diabetes, resolved childhood atopic dermatitis, hypothyroidism, orhyperthyroidism that is clinically euthyroid at Screening are allowed). Otherexceptions may be allowed following discussion with the Sponsor Medical Monitor forpatients who have not received treatment for their autoimmune disorder in the past 3years

10. Known active central nervous system metastases and/or carcinomatous meningitis.Patients with previously treated brain metastases may participate provided they areclinically stable for at least 4 weeks prior to study entry and have no evidence ofnew or enlarging brain metastases.

11. Unresolved toxicities from prior anticancer therapy, defined as not resolved tobaseline or to Grade 1 (NCI 2017), except for alopecia, peripheral neuropathy, andhypothyroidism secondary to prior therapy if currently being treated and clinicallyeuthyroid.

12. Receipt of any investigational agent or treatment within 21 days or 5 half-lives,whichever is shorter, before the first dose of study drug.

13. Any prior immunotherapy or treatment with checkpoint inhibitors within a period of 5half-lives (or 3 months, whichever is shorter) since the last dose of the therapy.

14. Use of systemic steroids > 10 mg/day prednisone (or equivalent) within 10 days ofenrollment, except for local (topical, nasal, or inhaled) steroid use. Limited dosesof systemic steroids (e.g., in patients with exacerbation of reactive airwaydisease) must have completed at least 10 days before enrollment. Steroid use toprevent IV contrast allergic reaction or anaphylaxis in patients who have knowncontrast allergies is allowed at any time before enrollment.

15. Active known second malignancy with the exception of any of the following:

• Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin,or in situ cervical cancer

• Adequately treated Stage I cancer from which the patient is currently inremission and has been in remission for ≥ 2 years;

• Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 ng/mL; or

• Any other cancer from which the patient has been disease-free for ≥ 2 years.

16. Use of biotin (i.e., vitamin B7) or supplements containing biotin higher than thedaily adequate intake of 30 μg (FDA 2019) (Note: Patients who switch from a highdose to a dose of 30 μg/day or less are eligible for study entry)

17. Any of the following within 6 months before Baseline Day 1:

• Myocardial infarction;

• Unstable angina;

• Unstable symptomatic ischemic heart disease;

• New York Heart Association (NYHA) class III or IV heart failure;

• Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, orsymptomatic cerebrovascular events);

• Any other significant cardiac condition (e.g., pericardial effusion,restrictive cardiomyopathy, severe untreated valvular stenosis, long QTcsyndrome, or severe congenital heart disease).