Safety/Efficacy Study of CID-078 in Patients With Advanced Solid Tumor Malignancies

Part 1a/1b Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible to participate in this study.

1. Solid tumor malignancy meeting the following criteria:

• Part 1a Dose Escalation and Part 1b New Formulation Dose Escalation/Pilot FoodEffect Cohort: locally advanced or metastatic solid tumor malignancy that hasprogressed or was non responsive to available therapies and for which nostandard or available curative therapy exists.

• Part 1a and Part 1b Backfill: patients with TNBC, SCLC, and solid tumorsharboring a RB1 or CDKN2A/B loss genomic alteration or Rb protein LoF.Additional tumor types or genomic alterations may be considered by the SRC asdata become available. Patient must have progressed or was non-responsive toavailable therapies and for which no standard or available curative therapyexists

2. Measurable disease per RECIST v1.1.

3. Age ≥ 18 years.

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

5. Life expectancy > 12 weeks.

6. Able to undergo a fresh biopsy if medically feasible.

7. Ability to swallow capsules by mouth.

8. Have the following laboratory values:

9. Calculated creatinine clearance (CrCl) ≥ 60 mL/min/1.73 m^2 by Cockroft-Gaultformula (actual body weight must be used for CrCl unless body mass index [BMI]is > 30 kg/m2, then lean or ideal body weight must be used (based oninstitutional practice), or estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73 m2 based alternative methods of determination (e.g., modificationof diet in renal disease [MDRD], 24-hour urine collection) if consistent withlocal or institutional practice.

10. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) unless prior history ofGilbert's syndrome with Sponsor Medical Monitor approval.

11. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN ifdue to liver involvement by tumor.

12. Hemoglobin ≥ 9.0 g/dL (last transfusion > 14 days prior to first dose of studydrug).

13. Platelets ≥ 100 × 10^9 cells/L (last platelet transfusion > 14 days prior tofirst dose of study drug).

14. Absolute neutrophil count ≥ 1.2 × 10^9 cells/L (last dose of hematopoieticgrowth factors > 14 days from first dose of study drug).

15. Females of childbearing potential must commit to sexual abstinence or to use twoacceptable forms of birth control (defined as the use of an intrauterine device, abarrier method with spermicide, condoms, or any form of hormonal contraceptives) forthe duration of the study and for four months following the last dose of studytreatment. Females who are at least two years postmenopausal or premenopausal withdocumented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, orpermanent infertility due to alternate medical causes other than above are notconsidered females of childbearing potential. Male patients must be sterile (biologically or surgically), commit to sexual abstinence or to the use of areliable method of birth control (condoms with spermicide) for the duration of thestudy and for four months following the last dose of study treatment.

16. Females of childbearing potential must have a negative serum pregnancy test duringScreening and a negative urine or serum pregnancy test prior to receiving the firstdose of study drug. Females who are at least two years postmenopausal orpremenopausal with documented hysterectomy, bilateral salpingectomy, bilateraloophorectomy, or permanent infertility due to alternate medical causes other thanabove are not considered females of childbearing potential.

17. Signed and dated Institutional Review Board (IRB)/Ethics Committee (EC)-approved ICFbefore any protocol-directed screening procedures are performed. Part 1b Pilot Food Effect Cohort - Specific Inclusion Criteria Patients who consent to participate in the pilot food effect cohort will also berequired to meet the following inclusion criteria:

18. Able to eat a standardized high-fat, high-caloric or low-fat meal (as applicable tothe food effect cohort assigned) within 25 minutes.

Exclusion Criteria:

A patient who meets any of the following exclusion criteria will be ineligible to participate in this study:

1. Treatment with any of the following:

2. Targeted therapy ≤ eight days or 5× the terminal phase elimination half-lives,whichever is shorter, prior to the first dose of study drug.

3. Systemic anticancer treatment (excluding targeted therapy as described above) ≤ 14 days prior to first dose of study drug.

4. Radiotherapy ≤ 28 days and palliative radiation ≤ 14 days prior to the firstdose of study drug. If irradiated, lesions must have demonstrated clear-cutprogression prior to being eligible for evaluation as target lesions.

5. Immunotherapy ≤ 28 days prior to the first dose of study drug.

6. Major surgery ≤ 28 days prior to the first dose of study drug.

7. Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment,except for alopecia and skin pigmentation. Patients with chronic, but stable Grade 2toxicities may be allowed to enroll after agreement between the Investigator andSponsor Medical Monitor.

8. Have known or suspected brain metastases or spinal cord compression, unless thecondition has been asymptomatic, treated with surgery and/or radiation, and has beenstable without requiring escalating doses of corticosteroids or anti-convulsantmedications for at least four weeks prior for the first dose of study drug.

9. Prior therapy with CID-078.

10. Known hypersensitivity to CID-078 or any drugs similar in structure or class.

11. Past medical history of interstitial lung disease, or any evidence of clinicallyactive interstitial lung disease. Patients with sub-clinical pneumonitis who havereceived anti-cancer therapy (e.g., immunotherapy, ADC) previously can be includedif their condition is stable without any medical intervention.

12. Patient has a history of congestive heart failure (CHF) Class III/IV according tothe New York Heart Association (NYHA) Functional Classification or serious cardiacarrhythmias requiring treatment.

13. Heart rate corrected QT (QTc) interval (using Fridericia correction calculation) > 470 msec.

14. Current treatment with medication known to prolong the QT/QTc interval (see examplesfrom Table 28) or history of additional risk factors for Torsade de Pointes (e.g.,heart failure, Grade ≥ 3 hypokalemia, family history of long QT syndrome). Patientwho has adequately controlled condition or requires use of medications from Table 28may be allowed upon agreement by the Investigator and Sponsor Medical Monitor.

15. Pregnant or lactating women.

16. History of another primary malignancy ≤ two years prior to starting study drug,except for adequately treated cancer (e.g., basal, or squamous cell carcinoma of theskin or cancer of the cervix in situ).

17. Malabsorption syndrome or other conditions (e.g., refractory nausea and vomiting,external biliary diversion, or any significant small bowel resection) that mayinterfere with adequate absorption of investigational product.

18. Uncontrolled intercurrent illness including, but not limited to, uncompensatedrespiratory, cardiac, hepatic, or renal disease, active infection (includinguntreated human immunodeficiency virus [HIV] and active clinical tuberculosis),symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,or psychiatric illness/social situations that would limit compliance with studyrequirements.

19. Current endocrinopathies, unless in the opinion of the Investigator, endocrinecomplications are stable and well controlled and study participation does notjeopardize patient's health and wellbeing. Patients with asymptomatic endocrinedisease on endocrine replacement therapy are eligible.

20. Active hepatitis B infection as defined by a positive hepatitis B surface antigen (HbsAg) test and detectable hepatitis B virus (HBV) DNA. Patients ineligible due todetectable levels of HBV DNA at baseline may be rescreened for enrollment if theirHBV DNA levels become undetectable after treatment with antiviral agents, and uponagreement between the Investigator and Sponsor Medical Monitor.

21. Active hepatitis C infection as defined by a reactive hepatitis C virus (HCV)antibody test and detectable HCV RNA.

22. For patients with a history of HIV or acquired immunodeficiency syndrome (AIDS):

23. Must have a CD4+ T-cell count ≥ 350 cells/μL

24. Have not had an opportunistic infection within the previous 12 months.

25. To be on current antiretroviral therapy (ART) regimen for a minimum of fourweeks and have an HIV viral load < 400 copies/mL at the time of enrollment.

26. Patients who are using concurrent strong cytochrome P450 (CYP)3A4 inhibitors (e.g., ritonavir, cobicistat) or strong CYP3A4 inducers are excluded from thestudy if their regimen cannot be altered. Otherwise, eligible study patientscould be switched to an alternate effective ART before study participation.

27. Current treatment with a strong CYP3A4 inhibitor or inducer, Pgp inhibitor, orCYP3A4 sensitive substrate within 14 days or five terminal half-lives prior to thefirst dose of study drug, whichever is shorter.

28. Active bleeding disorders.

29. Prior solid organ transplantation.

30. Is, in the Investigator's opinion, unable or unwilling to comply with the studyprocedures.

31. Have any condition or illness that, in the opinion of the Investigator, mightcompromise patient safety or interfere with the evaluation of the safety of thestudy drug.

Study Population (Part 2 Dose Expansion):

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible to participate in this study.

1. Advanced or metastatic solid tumor malignancy that has progressed or was nonresponsive to available therapies and for which no standard or available curativetherapy exists.

2. Triple negative breast cancer (TNBC) cohort: histologically or cytologicallyconfirmed TNBC per American Society for Clinical Oncology/College of AmericanPathologists (ASCO/CAP) criteria, based on the most recent analyzed biopsy orother pathology specimen.

3. Small cell lung cancer (SCLC) cohort: histologically or cytologically confirmedrelapsed/refractory SCLC.

4. Retinoblastoma 1 (RB1)-altered solid tumor cohort: solid tumors harboring adocumented RB1 genomic alteration or Rb protein LoF, as identified throughassays performed at Clinical Laboratory Improvement Amendments (CLIA)-certifiedor other similarly certified laboratories.

5. Patients must have measurable disease by RECIST v1.1.

6. Age ≥ 12 years and at least 40 kg in body weight.

7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (patients ≥ 18years of age), Karnofsky performance status ≥ 70% (patients ≥ 16 to < 18 years ofage), or Lansky performance status ≥ 70% (patients < 16 years of age). Patients whoare unable to walk because of paralysis, but who can sit in a wheelchair, will beconsidered ambulatory for the purpose of assessing the performance score (Appendix 1).

8. Life expectancy >12 weeks.

9. For patients ≥ 18 years of age: able to undergo a fresh biopsy if medicallyfeasible.

10. Ability to swallow capsules by mouth.

11. Have the following laboratory values:

12. For patients ≥ 18 years of age: calculated CrCl ≥ 60 mL/min/1.73 m2 byCockroft-Gault formula (actual body weight must be used for CrCl unless BMI > 30 kg/m2 then lean or ideal body weight must be used based on institutionalpractice), or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2based alternative methods of determination (e.g., modification of diet in renaldisease [MDRD], 24-hour urine collection) if consistent with local orinstitutional practice. For patients < 18 years of age: serum creatinine withinnormal limits (as defined below) or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 based on local institutional practice for determination.Age at Screening Maximum Serum Creatinine SI Unit age 12 to < 15 years - 0.81mg/dL; age 15 to < 18 years (male) - 1.08 mg/dL; age 15 to < 18 years (female)

• 0.84 mg/dL

2. Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome withSponsor Medical Monitor approval.

3. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN ifdue to liver involvement by tumor.

4. Hemoglobin ≥ 9.0 g/dL (last transfusion > 14 days prior to first dose of studydrug).

5. Platelets ≥ 100 × 10^9 cells/L (last platelet transfusion > 14 days prior tofirst dose of study drug).

6. Absolute neutrophil count ≥ 1.2 ×10^9 cells/L (last dose of hematopoieticgrowth factors > 14 days from first dose of study drug).

7. Females of childbearing potential must commit to sexual abstinence or to use twoacceptable forms of birth control (defined as the use of an intrauterine device, abarrier method with spermicide, condoms, any form of hormonal contraceptives) forthe duration of the study and for four months following the last dose of studytreatment. Females who are at least two years postmenopausal or premenopausal withdocumented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, orpermanent infertility due to alternate medical causes other than above are notconsidered females of childbearing potential. Male patients must be sterile (biologically or surgically), commit to sexual abstinence or to the use of areliable method of birth control (condoms with spermicide) for the duration of thestudy and for four months following the last dose of study treatment.

8. Females of childbearing potential must have a negative serum pregnancy test duringScreening and a negative urine or serum test prior to receiving first dose of studydrug. Females who are at least two years postmenopausal or premenopausal withdocumented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, orpermanent infertility due to alternate medical causes other than above are notconsidered females of childbearing potential.

9. Signed and dated IRB/EC-approved ICF for potential patients ≥ 18 years of age. Asigned and dated IRB/EC-approved adolescent assent form may also be required forpatients 12 to 17 years of age in addition to an ICF signed by a parent or legalguardian.

Exclusion Criteria:

A patient who meets any of the following exclusion criteria will be ineligible to participate in this study.

1. Treatment with any of the following:

2. Targeted therapy ≤ eight days or 5× the terminal phase elimination half-lives,whichever is shorter, prior to the first dose of study drug.

3. Systemic anticancer treatment (excluding targeted therapy as described above) ≤ 14 days prior to the first dose of study drug.

4. Radiotherapy ≤ 28 days and palliative radiation ≤ 14 days prior to the firstdose of study drug. If irradiated, lesions must have demonstrated clear-cutprogression prior to being eligible for evaluation as target lesions.

5. Immunotherapy ≤ 28 days prior to the first dose of study drug.

6. Major surgery ≤ 28 days prior to the first dose of study drug.

7. Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment,except for alopecia and skin pigmentation. Patients with chronic, but stable Grade 2toxicities may be allowed to enroll after agreement between the Investigator andSponsor Medical Monitor.

8. Have known or suspected brain metastases or spinal cord compression, unless thecondition has been asymptomatic, treated with surgery and/or radiation, and has beenstable without requiring escalating doses of corticosteroids or anti-convulsantmedications for at least four weeks prior to the first dose of study drug.

9. Prior therapy with CID-078.

10. Known hypersensitivity to CID-078 or any drugs similar in structure or class.

11. Past medical history of interstitial lung disease or any evidence of clinicallyactive interstitial lung disease. Patients with sub-clinical pneumonitis who havereceived anti-cancer therapy (e.g., immunotherapy, ADC) previously can be includedif their condition is stable without any medical intervention.

12. Patient has a history of CHF Class III/IV according to the NYHA FunctionalClassification Appendix 2) or serious cardiac arrhythmias requiring treatment.

13. QTc interval (using Fridericia correction calculation) (QTcF) > 470 msec.

14. Current treatment with medication known to prolong the QT/QTcF interval or historyof additional risk factors for Torsade de Pointes (e.g., heart failure, Grade ≥ 3hypokalemia, family history of long QT syndrome). Patient who has adequatelycontrolled condition or require use of medications from Table 28 may be allowed toenroll upon agreement by the Investigator and Sponsor Medical Monitor.

15. Pregnant or lactating women.

16. History of another primary malignancy ≤ two years prior to starting study drug,except for adequately treated cancer (e.g., basal or squamous cell carcinoma of theskin or cancer of the cervix in situ).

17. Malabsorption syndrome or other conditions (e.g., refractory nausea and vomiting,external biliary diversion, or any significant small bowel resection) that mayinterfere with adequate absorption of investigational product.

18. Uncontrolled intercurrent illness including, but not limited to, uncompensatedrespiratory, cardiac, hepatic, or renal disease, active infection (includinguntreated HIV and active clinical tuberculosis), symptomatic congestive heartfailure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/socialsituations that would limit compliance with study requirements.

19. Current endocrinopathies, unless in the opinion of the Investigator, endocrinecomplications are stable and well controlled and study participation does notjeopardize patient's health and wellbeing. Patients with asymptomatic endocrinedisease on endocrine replacement therapy are eligible.

20. Active hepatitis B infection as defined by a positive HBsAg test and detectable HBVDNA. Patients ineligible due to detectable levels of HBV DNA at baseline may berescreened for enrollment if their HBV DNA levels become undetectable aftertreatment with antiviral agents, and upon agreement between the Investigator andSponsor Medical Monitor.

21. Active hepatitis C infection as defined by a reactive HCV antibody test anddetectable HCV RNA.

22. For patients with a history of HIV or AIDS:

23. Must have a CD4+ T-cell count ≥ 350 cells/μL.

24. Have not had an opportunistic infection within the previous 12 months.

25. To be on current ART regimen for a minimum of four weeks and have an HIV viralload < 400 copies/mL at the time of enrollment.

26. Patients who are using concurrent strong CYP3A4 inhibitors (e.g., ritonavir,cobicistat) or strong CYP3A4 inducers are excluded from the study if theirregimen cannot be altered. Otherwise, eligible study patients could be switchedto an alternate effective ART regimen before study participation.

27. Current treatment with a strong CYP3A4 inhibitor or inducer, Pgp inhibitor, orCYP3A4 sensitive substrate as specifically listed in Table 26 and Table 27 within 14days or five terminal half-lives prior to the first dose of study drug, whichever isshorter.

28. Active bleeding disorders.

29. Prior solid organ transplantation.

30. Is, in the Investigator's opinion, unable or unwilling to comply with the studyprocedures.

31. Have any condition or illness that, in the opinion of the Investigator, mightcompromise patient safety or interfere with the evaluation of the safety of thestudy drug.