A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors

Inclusion Criteria:

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

2. Dazostinag SA (dose escalation Part 1A): o With histologically confirmed (cytological diagnosis is acceptable) advanced ormetastatic solid tumors that have no standard therapeutic options or are intolerantto these therapies.

3. Dazostinag in combination with pembrolizumab (dose escalation Parts 1B and Japansafety lead-in):

• With histologically confirmed (cytological diagnosis is acceptable) advanced ormetastatic solid tumors that have no standard therapeutic options or areintolerant to them, including:

• Tumors that have relapsed or are refractory to anti-programmed cell deathligand protein 1 (anti PD-(L)-1) therapy.

• Tumors that are naive to anti-PD-(L)-1 therapy.

4. For expansion phase only:

• SCCHN (Part 2):

• Participants with histologically confirmed (cytological diagnosis isacceptable) metastatic or recurrent, unresectable SCCHN that is consideredincurable by local therapies. Participants should not have had prior systemictherapy administered in the recurrent or metastatic setting. Systemic therapywhich was completed more than 6 months before signing consent if given as partof multimodal treatment of locally advanced disease is allowed.

• Anatomic subsites to be included are oral cavity, oropharynx, hypopharynx,larynx, nasal cavity, and paranasal sinuses (maxillary, ethmoid, sphenoid, andfrontal). The exception to this is nasopharyngeal cancer and salivary glandtumors, which will not be included.

• Participants with oropharyngeal cancer or tumors arising in the paranasalsinuses (maxillary, ethmoid, sphenoid, and frontal) must agree to providearchival tissue for human papilloma virus (HPV) testing or if known, HPVtesting results (using CINtec® p16 Histology assay is preferred but notrequired) and a 70% cutoff point must be provided. Alternatively, archivaltissue or a fresh excisional or core needle biopsy (≥ 2 cores) is required forthe determination of HPV status. If HPV status was previously tested using thismethod (CINtec® p16 Histology assay is preferred but not required), noadditional testing is required. Archival tissue can be obtained up to 90 daysprior to screening. Samples that are older than 90 days at screening may beused after consultation with the sponsor.

• For Part 2A, tumors must have a PD-L1 CPS ≥ 1. Participants must agree toprovide fresh tumor biopsy for analysis from a core or excisional biopsy (fineneedle aspirate is not sufficient) at screening for PD-L1 CPS assessment by acentral laboratory. This specimen may be the diagnostic sample for participantswith a new diagnosis of metastatic SCCHN. Participants for whom newly obtainedsamples cannot be obtained (eg, inaccessible or participant safety concern) maysubmit an archived specimen only upon agreement from the Sponsor. Archivaltissue can be obtained up to 90 days prior to screening provided there was noother treatment from the time of biopsy until the start of study treatment. ForPart 2B, any CPS is eligible but fresh or archival tissue is required forconfirmation of CPS status. Collection of the tissue samples for PD-L1assessments for Part 2B can be discontinued by the sponsor if sufficient datahas been collected or dazostinag activity does not justify further collection.

• For Part 2B, participants must be eligible to receive treatment with eithercisplatin or carboplatin in combination with 5-fluorouracil (5-FU) per thetreating physician.

5. CRC (Part 3):

• Third-line or later MSI-H/dMMR CRC (Part 3A): Participants with histologicallyconfirmed (cytological diagnosis is acceptable) recurrent locally advanced ormetastatic MSI-H/dMMR CRC whose disease has progressed on or following therapywith 1) an anti-PD-1 or PD-L1 antibody (i.e., pembrolizumab) and 2) at leastone line of combination chemotherapy including a fluoropyrimidine andirinotecan OR oxaliplatin with or without an anti-epidermal growth factorreceptor (EGFR) or anti-vascular endothelial growth factor (VEGFR) monoclonalantibody (i.e., cetuximab or bevacizumab). MSI-H/dMMR CRC participants musthave received at least 6 weeks of prior treatment with an anti-PD-(L)-1antibody. Only one line of anti-PD-(L)-1 is permitted.

• Third-line MSS/pMMR CRC (Part 3B): Participants with histologically confirmed (cytological diagnosis is acceptable) recurrent locally advanced or metastaticMSS/pMMR CRC whose disease has progressed on or following therapy with 2different lines of combination chemotherapy, including therapy with afluoropyrimidine and irinotecan AND therapy with a fluoropyrimidine andoxaliplatin. Both lines of therapy may be given with or without an anti-EGFR oranti-VEGFR monoclonal antibody (i.e., cetuximab or bevacizumab). Participants with MSS/pMMR CRC must have progressed on or after combinationchemotherapy regimens containing BOTH irinotecan AND oxaliplatin.

• Participants with MSI-H/dMMR or MSS/pMMR CRC must have documented MSI/MMRstatus assessed by a Clinical Laboratory Improvements Amendment-certified (United States [US] sites or an accredited (outside of the US) local laboratoryusing immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) or nextgeneration sequencing (NGS) assay.

• Adequate tumor tissue available for central laboratory confirmation of MSI/MMRstatus. Note: confirmation of central test positivity is not required beforetreatment.

• Participants with MSI-H/dMMR or MSS/pMMR CRC must have been treated with 2prior lines of therapy in the recurrent locally advanced or metastatic setting.

6. Adequate bone marrow, renal, hepatic and cardiac functions.

7. Left ventricular ejection fraction (LVEF) > 50%, as measured by echocardiogram ormultiple-gated acquisition (MUGA) scan within 4 weeks before receiving the firstdose of study drug.

8. Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheralneuropathy, and/or autoimmune endocrinopathies with stable endocrine replacementtherapy.

9. In dose escalation Part 1, (not applicable for the Japan safety lead-in) onceperipheral evidence of dazostinag pharmacodynamic stimulation of the innate and/oradaptive immune system is observed in the blood and/or an imaging response/partialresponse (CR/PR) is observed in at least 1 participant, subsequent participantsmust:

• Have at least 1 lesion amenable for biopsy.

• Agree to have 2 tumor biopsies: 1 during the screening period and 1 while ondazostinag treatment.

10. Must have at least 1 RECIST version 1.1-evaluable (measurable) lesion. For the doseescalation phase (Part 1) only, nonmeasurable only disease is acceptable.

11. Pharmacokinetic (PK)/pharmacodynamic blood must be drawn on a peripherally-insertedcatheter. Dazostinag is preferentially administered through a central line, butperipheral infusion is acceptable. If a peripheral line is used for dazostinagand/or pembrolizumab infusion, it must be separate than the one used forPK/pharmacodynamic collection.

Exclusion Criteria:

1. Corrected QT interval by Fredericia (QTcF) greater than (>) 450 milliseconds (men)or > 475 milliseconds (women) on a 12-lead electrocardiogram (ECG) during thescreening period.

2. Grade greater than or equal to (≥) 2 hypotension (that is, hypotension for whichnonurgent intervention is required) at screening or during Cycle 0 Day 1 (C0D1) [forJapan safety lead-in only] and Cycle 1 Day 1 (C1D1) predose assessment.

3. Oxygen saturation less than (<) 92 percent (%) on room air at screening or duringC0D1 (for Japan safety lead-in only) and C1D1 predose assessment.

4. Treated with other STING agonists/antagonist and toll-like receptors agonists withinthe past 6 months.

5. Current history of pneumonitis, interstitial lung disease, severe chronicobstructive pulmonary disease, idiopathic pulmonary fibrosis, other restrictive lungdiseases, acute pulmonary embolism, or Grade ≥ 2 pleural effusion or ascites notcontrolled by tap or requiring indwelling catheters.

6. History of brain and leptomeningeal metastasis unless:

• Brain metastases are clinically and radiologically stable or improved (that is, ≥ 4 weeks) following surgery, whole-brain radiation, or stereotacticradiosurgery, AND

• Off corticosteroids.

7. Ongoing Grade ≥ 2 infection or participants with Grade ≥ 2 fever of malignantorigin.

8. Chronic, active hepatitis (example: participants with known hepatitis B surfaceantigen seropositive and/or detectable hepatitis C virus [HCV]- ribonucleic acid [RNA]).

9. For participants in the dose escalation SA Part 1A only: refusal of standardtherapeutic options.

10. For participants receiving pembrolizumab only: contraindication and/or intoleranceto the administration of pembrolizumab.

11. For participants receiving chemotherapy in Part 2B: contraindication and/orintolerance to the administration of both platinum agents (cisplatin andcarboplatin) and/or 5-FU.

12. Participant has had any other prior or concurrent malignancy within 2 years prior toenrollment with the following exceptions: adequately treated localized basal cell orsquamous cell carcinoma, or curatively treated in situ carcinoma of the cervix orbreast. Other exceptions may be considered upon sponsor consultation.

13. Concurrent chemotherapy (except for Part 2B), immunotherapy (except forpembrolizumab in Part 1B, Part 2, and Part 3), biologic, or hormonal therapy (exceptfor adjuvant endocrine therapy for a history of breast cancer). Concurrent use ofhormones for noncancer-related conditions is acceptable (except for corticosteroidhormones) unless allowed per exclusion criterion 16.

14. Radiation therapy within 14 days (42 days for radiation to the lungs) and/orsystemic treatment with radionuclides within 42 days before C1D1 of study drug(s).Participants with clinically relevant ongoing pulmonary complications from priorradiation therapy are not eligible.

15. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently orwithin 7 days of C1D1 of study drug(s), with the following exceptions:

• Topical, intranasal, inhaled, ocular, intra-articular, and/or othernon-systemic corticosteroids.

• Premedications required for computed tomography (CT) or magnetic resonanceimaging (MRI) scans.

• Physiological doses of replacement steroid therapy (example: for adrenalinsufficiency).

• For participants enrolled in Part 2B, chemotherapy premedication with steroidscan be administered according to local standards of care practice.

16. Use of medications that are known clinical organic anion-transporting polypeptide B1 (OATP1B1) and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of studydrug(s).

17. Receipt of live attenuated vaccine (eg, tuberculosis Bacillus Calmette-Guerinvaccine, oral polio vaccine, measles, rotavirus, yellow fever) within 28 days ofC1D1 of study drug(s).

18. Recipients of allogeneic or autologous stem cell transplantation or organtransplantation. For Part 2 SCCHN only:

19. Has progressive disease (PD) within 6 months of completion of curatively intendedsystemic treatment for locoregionally advanced SCCHN.

20. Has a life expectancy of less than 3 months and/or has rapidly PD (eg, tumorbleeding, uncontrolled tumor pain) in the opinion of the treating investigator.

21. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 oranti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent.

22. Participants with known dihydropyrimidine dehydrogenase (DPD) deficiency orthymidine phosphorylase gene (TYMP) mutations (Part 2B only).