A Clinical Study to Evaluate the Safety, Tolerability and Efficacy of IOS-1002 Administered Alone and in Combination with Pembrolizumab, a PD-1 Monoclonal Antibody in Advanced Solid Tumors

Inclusion Criteria:

1. Age ≥18 years old at the time of Screening (signing the informed consent form [ICF]).

2. Histologically or cytologically confirmed advanced solid tumor (metastatic and/orunresectable) with measurable disease per RECIST v1.1:

3. Malignancy that has relapsed or is refractory to, at least 1 standard treatmentregimen in the advanced or metastatic setting, if such a therapy exists or forwhich the subjects who refuse or are ineligible for standard therapy.

4. Subjects with lesions in a previously irradiated field as the sole site ofmeasurable disease will be permitted to enrol provided the lesions havedemonstrated clear progression and can be measured accurately.

5. For combination therapy dose-escalation: subjects who have undergone treatment withany agent specifically targeting checkpoint pathway inhibition (such as PD-1, PD-L1,PDL-2, LAG-3, or CTLA-4 antibody) for at least 3 months before disease progressionand must have a gap of at least 4 weeks from the last treatment before receivingstudy treatment on Cycle 1 Day 1 a. Subjects who experienced prior Grade 1 to 2 checkpoint therapy-related immunemediated AEs must have confirmed recovery from these events at the time of studyentry, other than endocrinopathies treated with supplementation. Where applicable,these subjects must also have completed steroid tapers for treatment of these AEs bya minimum of 14 days prior to commencing treatment with study therapy. b)Eligibility of subjects with prior Grade ≥3 checkpoint therapy-related immune AEs,will be considered on a case-by-case basis after discussion with the Medical Monitor (eg, asymptomatic isolated Grade 3 lipase elevations without clinical orradiological features of pancreatitis will be permitted to enrol).

6. Adequate organ function at Screening

7. Willingness to provide consent to allow the acquisition of fresh tumor biopsy and/orexisting formalin tissue sample

8. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

Exclusion Criteria:

1. Subjects with known or suspected CNS metastases, untreated CNS metastases, or withthe CNS as the only site of disease are excluded. EXCEPTION: Subjects withcontrolled brain metastases will be allowed to enroll. Controlled brain metastasesare defined as no radiographic progression for at least 4 weeks following radiationand/or surgical treatment (or 4 weeks of observation if no intervention isclinically indicated), and off steroids for at least 4 weeks prior to Screening, andno new or progressive neurological signs and symptoms.

2. Subjects with known carcinomatous meningitis.

3. Subjects with a prior malignancy except non-melanoma skin cancers, and in situcancers such as: bladder, colon, cervical/dysplasia, melanoma, or breast. Subjectswith other second malignancies diagnosed more than 2 years ago who have receivedtherapy with curative intent with no evidence of disease during the interval who areconsidered by the Investigator to present a low risk for recurrence will beeligible.

4. Subjects with active, known, or suspected autoimmune disease. Subjects withvitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmunecondition only requiring hormone replacement, euthyroid with a history of Grave'sdisease (subjects with suspected autoimmune thyroid disorders must be negative forthyroglobulin and thyroid peroxidase antibodies and thyroid-stimulatingimmunoglobulin prior to first dose of study treatment), psoriasis not requiringsystemic treatment, or conditions not expected to recur in the absence of anexternal trigger are permitted to enroll.

5. Subjects with interstitial lung disease that is symptomatic or may interfere withthe detection or management of suspected drug-related pulmonary toxicity, includingsubjects with pneumonitis.

6. Chronic Obstructive Pulmonary Disease (COPD) requiring recurrent steroids bursts orchronic steroids at doses greater than 10 mg/day of prednisone or the equivalent.

7. Uncontrolled or significant cardiovascular disease

8. Evidence of active infection ≤7 days prior to initiation of study treatment therapy (does not apply to viral infections that are presumed to be associated with theunderlying tumor type required for study entry).

9. Evidence or history of active or latent tuberculosis infection including purifiedprotein derivative recently converted to positive; chest x-ray with evidence ofinfectious infiltrate.

10. History of any chronic hepatitis

11. Known history of testing positive for HIV or known acquired immunodeficiencysyndrome. Note: Testing for HIV must be performed at Screening.

12. Any anticancer therapy (eg, chemotherapy, biologics, vaccines, or hormonaltreatment) including investigational drugs within 4 weeks prior to the first dose ofstudy treatment administration, except for GnRH agonist therapy for subjects withprostate cancer and anticancer therapies with half-life of <4 weeks eg, prior use ofEGFR TKI (completed at least two weeks prior to first dose of study treatment isacceptable).

13. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroiddoses >10 mg daily prednisone equivalent in the absence of active autoimmunedisease. Note: Treatment with a short course of steroids (<5 days) up to 7 daysprior to initiating study treatment is permitted.

14. Use of non-oncology vaccines containing live virus for prevention of infectiousdiseases within 12 weeks prior to study treatment. The use of inactivated seasonalinfluenza vaccines eg, Fluzone® will be permitted on study without restriction.

15. Any major surgery within 4 weeks of study treatment administration. Subjects musthave recovered from the effects of major surgery or significant traumatic injury atleast 14 days before the first dose of study treatment.

16. Prior organ allograft.

17. Use of packed red blood cells (pRBC) or platelet transfusion within 2 weeks prior tothe first dose of study treatment.

18. History of allergy to PD-1 mAb, significant drug allergy (such as anaphylaxis orhepatotoxicity) to prior anticancer immune modulating therapies (eg, checkpointinhibitors, T-cell costimulatory antibodies).

19. All toxicities attributed to prior anticancer therapy other than alopecia andfatigue must have resolved to Grade 1 (NCI CTCAE v5.0) or baseline beforeadministration of study treatment. Subjects with toxicities attributed to prioranticancer therapy which are not expected to resolve and result in long lastingsequelae, such as neuropathy after platinum-based therapy, are permitted to enroll.

20. Subjects with known HLA alloimmunization (not specifically tested for the trial)