Phase I Study of Tumor Treating Fields (TTF) in Combination With Cabozantinib or With Pembrolizumab and Nab-Paclitaxel in Patients With Advanced Solid Tumors Involving the Abdomen or Thorax

Inclusion Criteria:

• Participants must have pathologically confirmed advanced/metastatic solid cancer (hepatocellular carcinoma, renal cell carcinoma, breast cancer, ovarian/fallopian,or endometrial/primary peritoneal tumors) involving the abdomen or thorax, cannottolerate standard therapy or have experienced tumor progression on standard therapy.

• Age: ≥18 years.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• Life expectancy >3 months.

• Normal bone marrow function, defined as absolute neutrophil count ≥1,000/µL;platelets ≥75,000/µL; hemoglobin ≥8 g/dL.

• Adequate hepatic function as defined by a total bilirubin level ≤1.5 x the upperlimit of normal (ULN), unless the patient has known Gilbert's syndrome, and alanineaminotransferase (ALT)/ serum glutamic pyruvic transaminase levels (SGPT) ≤2.5 x ULN (unless the patient has liver metastases: ALT)/ serum glutamic pyruvic transaminaselevels (SGPT) ≤5 x ULN).

• Participants with HCC must have a Child Pugh status A, no clinically significantascites (requiring pharmacological or interventional treatment), and no history (orincreased risk) of esophageal/gastric bleeding, impaired wound healing, perforationor fistula.

• Serum creatinine clearance ≥50 mL/min by the Cockcroft-Gault formula.

• Measurable disease by RECIST or evaluable disease.

• Contraception: Women of childbearing potential must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry and for the duration of study participation. Childbearing potential willbe defined as women who have had menses within the past 12 months and who have nothad a tubal ligation, hysterectomy, or bilateral oophorectomy. Should a woman becomepregnant or suspect that she is pregnant while participating in this study, sheshould inform her treating physician immediately. Male participants must agree touse effective contraception or abstinence while on study.

• Able to operate the TTF device independently or with the help of a caregiver.

Exclusion Criteria:

• Participants must not receive prior anticancer therapy or radiation therapy within 2weeks and must not undergo major surgery within 4 weeks prior to initiation oftreatment on protocol. Participants who are already on cabozantinib and haveprogressive disease are allowed to transition to treatment with tumor treatingfields and cabozantinib. Participants in both cohorts who already started treatmentsas standard of care (Cohort 1: Cabozantinib and Cohort 2: nab-paclitaxel andPembrolizumab) are allowed to start on protocol within the first 2-3 weeks oftreatment initiation. Palliative radiation therapy is allowed.

• Participants must have recovered to Grade 0-1 toxicity from prior therapy.

• Active brain metastasis or leptomeningeal disease. Patients with treated brainmetastasis must have stable disease, evidenced by brain imaging for at least 4 weeksand the patient must have been off steroids for at least 2 weeks.

• The patient has cardiac conditions as follows: uncontrolled: hypertension (bloodpressure [BP] > 160/100) despite optimal therapy, uncontrolled angina, ventriculararrhythmias, congestive heart failure (New York Heart Association Class II orabove), prior or current cardiomyopathy, uncontrolled atrial fibrillation with heartrate > 100 beats per minute (bpm), unstable ischemic heart disease (myocardialinfarction within 6 months prior to starting treatment or angina requiring use ofnitrates more than once weekly).

• The patient has concurrent severe and/or uncontrolled medical disease that couldcompromise participation in the study (i.e., uncontrolled diabetes, severe infectionrequiring active treatment, severe malnutrition, chronic severe liver or renaldisease).

• Concurrent malignancies are permitted if (A) they were previously treated, and alltreatment of that malignancy was completed at least 2 years before enrollment and noevidence of disease exists, or (B) with agreement from the Principal Investigator (PI), participants who have a concurrent malignancy that is clinically stable anddoes not require tumor-directed treatment are eligible to participate if the risk ofthe prior malignancy interfering with either safety or efficacy endpoints is verylow, or (C) with agreement from the PI, other malignancies may be permitted if therisk of the prior malignancy interfering with either safety or efficacy end pointsis very low. Adequately treated basal or squamous cell carcinoma or carcinoma insitu is allowed.

• The patient is pregnant or breastfeeding.

• History of hypersensitivity or contraindication to TTF.

• Implanted pacemaker, defibrillator or other electrical medical devices.

• The participant has a previously-identified allergy or hypersensitivity tocabozantinib, nab-paclitaxel, or pembrolizumab, medical adhesives or hydrogel or thepatient has received prior cabozantinib and discontinued therapy due to unacceptabletoxicity.

• Any other condition that would, in the investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns or compliancewith clinical study procedures.

• The patient is unable or unwilling to abide by the study protocol or cooperate fullywith the investigator or designee.

• CABOZANTINIB COHORT ONLY: The patient has experienced clinically-significanthematemesis or hemoptysis of > 0.5 teaspoon of red blood, or other signs indicativeof pulmonary hemorrhage within 3 months before the first dose of study treatment.

• CABOZANTINIB COHORT ONLY: The patient has a cavitating pulmonary lesion(s) or apulmonary lesion abutting or encasing a major blood vessel.

• CABOZANTINIB COHORT ONLY: The patient has received drugs used to control loss ofbone mass within 4 weeks prior to the first dose of study treatment.

• CABOZANTINIB COHORT ONLY: The patient has prothrombin time/international normalizedratio (PT/INR) or partial thromboplastin time (PTT) test results that are above (1.3X) the laboratory upper limit of normal.

• CABOZANTINIB COHORT ONLY: The subject has a corrected QT interval (QTcF) > 450 msfor men or > 470 ms for women.

• CABOZANTINIB COHORT ONLY: The patient requires concomitant treatment, in therapeuticdoses, with anticoagulants such as warfarin or Coumadin-related agents, heparin,thrombin or FXa inhibitors, and antiplatelet agents. Low-dose aspirin (≤ 81 mg/day),low dose warfarin (≤ 1mg/day), and prophylactic low molecular weight heparin (LMWH)are permitted.

• CABOZANTINIB COHORT ONLY: Patients with encasement of a major artery or bowel bytumor are excluded.

• CABOZANTINIB COHORT ONLY: The patient is unable to swallow capsules.

• CABOZANTINIB COHORT ONLY: History of hypersensitivity or contraindication tocabozantinib.

• ATEZOLIZUMAB-CONTAINING COHORT: Participants who have received prior immunotherapy,including prior anti-PD-1 or anti-PD-L1 therapies may participate: (A) only if theirprior anti-PD-1 or anti-PDL1 monotherapy or combination therapy were NOT the lasttreatment prior to participation on this study. (B) Participants who had priorimmunotherapies and experienced Grade 1-2 immune-related adverse event (irAE) musthave documentation that their irAEs are Grade 1 or 0 using current CommonTerminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and participants must beoff steroid therapy and/or other immunosuppressive therapy, as treatment for irAEs,for >= 14 days from Cycle 1, Day 1. (C) Participants who experienced Grade 3 irAEsconsisting of laboratory abnormalities that were asymptomatic and have now resolvedto Grade 1 or 0 and participants who have been off steroid and/or otherimmunosuppressive therapy, as treatment for irAEs, for >= 30 days from Cycle 1, Day

1. Participants with prior irAE pneumonitis (>= Grade 2) should not be givenatezolizumab.

• ATEZOLIZUMAB-CONTAINING COHORT: Human immunodeficiency virus (HIV) infection, activeHepatitis B or C infection, or active infections requiring oral or intravenousantibiotics.

• ATEZOLIZUMAB-CONTAINING COHORT: Has received a live vaccine within 30 days prior tofirst dose.

• ATEZOLIZUMAB-CONTAINING COHORT: Active diverticulitis, intra-abdominal abscess,gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known riskfactors for bowel perforation.

• ATEZOLIZUMAB-CONTAINING COHORT: Serious autoimmune disease at the discretion of thetreating attending: Patients with a history of active serious inflammatory boweldisease (including Crohn's disease and ulcerative colitis) and autoimmune disorderssuch as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemiclupus erythematosus or autoimmune vasculitis (e.g. Wegener's Granulomatosis) areexcluded from this study.

• ATEZOLIZUMAB-CONTAINING COHORT: History of/or current immunodeficiency disease orprior treatment compromising immune function at the discretion of the treatingphysician.