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 Food
Effect Cohort: locally advanced or metastatic solid tumor malignancy that has
progressed or was non responsive to available therapies and for which no
standard or available curative therapy exists.
- - Part 1a Backfill: patients with TNBC, SCLC, and solid tumors harboring a RB1
genomic alteration or Rb protein LoF.
Patient must have progressed or was
non-responsive to available therapies and for which no standard or available
curative therapy exists. 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 (preferred). If biopsy is deemed not medically safe,
archival tumor tissue may be used instead. If archival tumor tissue or fresh biopsy
sample is not available, enrollment may be considered on a case-by-case basis
following a discussion between the Investigator and the Sponsor Medical Monitor.
7. Ability to swallow capsules by mouth.
8. Have the following laboratory values:
1. Calculated creatinine clearance (CrCl) ≥ 60 mL/min/1.73 m^2 (by Cockroft-Gault
formula); 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 on
institutional practice).
2. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) unless prior history of
Gilbert's syndrome with Sponsor Medical Monitor approval.
3. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if
due to liver involvement by tumor.
4. Hemoglobin ≥ 9.0 g/dL (last transfusion > 14 days prior to first dose of study
drug).
5. Platelets ≥ 100 × 10^9 cells/L (last platelet transfusion > 14 days prior to
first dose of study drug).
6. Absolute neutrophil count ≥ 1.2 × 10^9 cells/L (last dose of hematopoietic
growth factors > 14 days from first dose of study drug).
9. Females of childbearing potential must commit to sexual abstinence or to use two
acceptable forms of birth control (defined as the use of an intrauterine device, a
barrier method with spermicide, condoms, or any form of hormonal contraceptives) for
the duration of the study and for four months following the last dose of study
treatment. Females who are at least two years postmenopausal or premenopausal with
documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or
permanent infertility due to alternate medical causes other than above are not
considered females of childbearing potential. Male patients must be sterile
(biologically or surgically), commit to sexual abstinence or to the use of a
reliable method of birth control (condoms with spermicide) for the duration of the
study and for four months following the last dose of study treatment.
10. Females of childbearing potential must have a negative serum pregnancy test during
Screening and a negative urine or serum pregnancy test prior to receiving the first
dose of study drug. Females who are at least two years postmenopausal or
premenopausal with documented hysterectomy, bilateral salpingectomy, bilateral
oophorectomy, or permanent infertility due to alternate medical causes other than
above are not considered females of childbearing potential.
11. Signed and dated Institutional Review Board (IRB)/Ethics Committee (EC)-approved ICF
before 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 be
required to meet the following
inclusion criteria:
12. Able to eat a standardized high-fat, high-caloric or low-fat meal (as applicable to
the 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:
1. Targeted therapy ≤ eight days or 5× the terminal phase elimination half-lives,
whichever is shorter, prior to the first dose of study drug.
2. Systemic anticancer treatment (excluding targeted therapy as described above) ≤
14 days prior to first dose of study drug.
3. Radiotherapy ≤ 28 days and palliative radiation ≤ 14 days prior to the first
dose of study drug. If irradiated, lesions must have demonstrated clear-cut
progression prior to being eligible for evaluation as target lesions.
4. Immunotherapy ≤ 28 days prior to the first dose of study drug.
5. Major surgery ≤ 28 days prior to the first dose of study drug.
2. Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment,
except for alopecia and skin pigmentation. Patients with chronic, but stable Grade 2
toxicities may be allowed to enroll after agreement between the Investigator and
Sponsor Medical Monitor.
3. Have known or suspected brain metastases or spinal cord compression, unless the
condition has been asymptomatic, treated with surgery and/or radiation, and has been
stable without requiring escalating doses of corticosteroids or anti-convulsant
medications for at least four weeks prior for the first dose of study drug.
4. Prior therapy with CID-078.
5. Known hypersensitivity to CID-078 or any drugs similar in structure or class.
6. Past medical history of interstitial lung disease, or any evidence of clinically
active interstitial lung disease. Patients with sub-clinical pneumonitis who have
received anti-cancer therapy (e.g., immunotherapy, ADC) previously can be included
if their condition is stable without any medical intervention.
7. Patient has a history of congestive heart failure (CHF) Class III/IV according to
the New York Heart Association (NYHA) Functional Classification or serious cardiac
arrhythmias requiring treatment.
8. Heart rate corrected QT (QTc) interval (using Fridericia correction calculation) >
470 msec.
9. Current treatment with medication known to prolong the QT/QTc interval (see examples
from 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). Patient
who has adequately controlled condition or requires use of medications from Table 28
may be allowed upon agreement by the Investigator and Sponsor Medical Monitor.
10. Pregnant or lactating women.
11. 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 the
skin or cancer of the cervix in situ).
12. Malabsorption syndrome or other conditions (e.g., refractory nausea and vomiting,
external biliary diversion, or any significant small bowel resection) that may
interfere with adequate absorption of investigational product.
13. Uncontrolled intercurrent illness including, but not limited to, uncompensated
respiratory, cardiac, hepatic, or renal disease, active infection (including
untreated 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 study
requirements.
14. Current endocrinopathies, unless in the opinion of the Investigator, endocrine
complications are stable and well controlled and study participation does not
jeopardize patient's health and wellbeing. Patients with asymptomatic endocrine
disease on endocrine replacement therapy are eligible.
15. 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 to
detectable levels of HBV DNA at baseline may be rescreened for enrollment if their
HBV DNA levels become undetectable after treatment with antiviral agents, and upon
agreement between the Investigator and Sponsor Medical Monitor.
16. Active hepatitis C infection as defined by a reactive hepatitis C virus (HCV)
antibody test and detectable HCV RNA.
17. For patients with a history of HIV or acquired immunodeficiency syndrome (AIDS):
1. Must have a CD4+ T-cell count ≥ 350 cells/μL. 2. Have not had an opportunistic infection within the previous 12 months.
3. To be on current antiretroviral therapy (ART) regimen for a minimum of four
weeks and have an HIV viral load < 400 copies/mL at the time of enrollment.
4. Patients who are using concurrent strong cytochrome P450 (CYP)3A4 inhibitors
(e.g., ritonavir, cobicistat) or strong CYP3A4 inducers are excluded from the
study if their regimen cannot be altered. Otherwise, eligible study patients
could be switched to an alternate effective ART before study participation.
18. Current treatment with a strong CYP3A4 inhibitor or inducer, Pgp inhibitor, or
CYP3A4 sensitive substrate within 14 days or five terminal half-lives prior to the
first dose of study drug, whichever is shorter.
19. Active bleeding disorders.
20. Prior solid organ transplantation.
21. Is, in the Investigator's opinion, unable or unwilling to comply with the study
procedures.
22. Have any condition or illness that, in the opinion of the Investigator, might
compromise patient safety or interfere with the evaluation of the safety of the
study 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 non
responsive to available therapies and for which no standard or available curative
therapy exists.
1. Triple negative breast cancer (TNBC) cohort: histologically or cytologically
confirmed TNBC per American Society for Clinical Oncology/College of American
Pathologists (ASCO/CAP) criteria, based on the most recent analyzed biopsy or
other pathology specimen.
2. Small cell lung cancer (SCLC) cohort: histologically or cytologically confirmed
relapsed/refractory SCLC.
3. Retinoblastoma 1 (RB1)-altered solid tumor cohort: solid tumors harboring a
documented RB1 genomic alteration or Rb protein LoF, as identified through
assays performed at Clinical Laboratory Improvement Amendments (CLIA)-certified
or other similarly certified laboratories.
2. Patients must have measurable disease by RECIST v1.1.
3. Age ≥ 12 years and at least 40 kg in body weight.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (patients ≥ 18
years of age), Karnofsky performance status ≥ 70% (patients ≥ 16 to < 18 years of
age), or Lansky performance status ≥ 70% (patients < 16 years of age). Patients who
are unable to walk because of paralysis, but who can sit in a wheelchair, will be
considered ambulatory for the purpose of assessing the performance score (Appendix
1).
5. Life expectancy >12 weeks.
6. Able to undergo a fresh biopsy (preferred). If biopsy is deemed not medically safe,
archival tumor tissue sample may be used instead. If archival tumor tissue or fresh
biopsy sample is not available, enrollment may be considered on a case-by-case basis
following a discussion between the Investigator and the Sponsor Medical Monitor.
7. Ability to swallow capsules by mouth.
8. Have the following laboratory values:
1. For patients ≥ 18 years of age: calculated CrCl ≥ 60 mL/min/1.73 m^2 (by
Cockroft-Gault formula); actual body weight must be used for CrCl unless BMI >
30 kg/m^2 then lean or ideal body weight must be used (based on institutional
practice). For patients < 18 years of age: serum creatinine within normal
limits (as defined below) or estimated glomerular filtration rate (eGFR) ≥ 60
mL/min/1.73 m^2 based on local institutional practice for determination.
Age at Screening Maximum Serum Creatinine SI Unit age 12 to < 15 years
- - 0.81
mg/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 with
Sponsor Medical Monitor approval.
3. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if
due to liver involvement by tumor.
4. Hemoglobin ≥ 9.0 g/dL (last transfusion > 14 days prior to first dose of study
drug).
5. Platelets ≥ 100 × 10^9 cells/L (last platelet transfusion > 14 days prior to
first dose of study drug).
6. Absolute neutrophil count ≥ 1.2 ×10^9 cells/L (last dose of hematopoietic
growth factors > 14 days from first dose of study drug).
9. Females of childbearing potential must commit to sexual abstinence or to use two
acceptable forms of birth control (defined as the use of an intrauterine device, a
barrier method with spermicide, condoms, any form of hormonal contraceptives) for
the duration of the study and for four months following the last dose of study
treatment. Females who are at least two years postmenopausal or premenopausal with
documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or
permanent infertility due to alternate medical causes other than above are not
considered females of childbearing potential. Male patients must be sterile
(biologically or surgically), commit to sexual abstinence or to the use of a
reliable method of birth control (condoms with spermicide) for the duration of the
study and for four months following the last dose of study treatment.
10. Females of childbearing potential must have a negative serum pregnancy test during
Screening and a negative urine or serum test prior to receiving first dose of study
drug. Females who are at least two years postmenopausal or premenopausal with
documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or
permanent infertility due to alternate medical causes other than above are not
considered females of childbearing potential.
11. Signed and dated IRB/EC-approved ICF for potential patients ≥ 18 years of age. A
signed and dated IRB/EC-approved adolescent assent form may also be required for
patients 12 to 17 years of age in addition to an ICF signed by a parent or legal
guardian.
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:
1. Targeted therapy ≤ eight days or 5× the terminal phase elimination half-lives,
whichever is shorter, prior to the first dose of study drug.
2. Systemic anticancer treatment (excluding targeted therapy as described above) ≤
14 days prior to the first dose of study drug.
3. Radiotherapy ≤ 28 days and palliative radiation ≤ 14 days prior to the first
dose of study drug. If irradiated, lesions must have demonstrated clear-cut
progression prior to being eligible for evaluation as target lesions.
4. Immunotherapy ≤ 28 days prior to the first dose of study drug.
5. Major surgery ≤ 28 days prior to the first dose of study drug.
2. Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment,
except for alopecia and skin pigmentation. Patients with chronic, but stable Grade 2
toxicities may be allowed to enroll after agreement between the Investigator and
Sponsor Medical Monitor.
3. Have known or suspected brain metastases or spinal cord compression, unless the
condition has been asymptomatic, treated with surgery and/or radiation, and has been
stable without requiring escalating doses of corticosteroids or anti-convulsant
medications for at least four weeks prior to the first dose of study drug.
4. Prior therapy with CID-078.
5. Known hypersensitivity to CID-078 or any drugs similar in structure or class.
6. Past medical history of interstitial lung disease or any evidence of clinically
active interstitial lung disease. Patients with sub-clinical pneumonitis who have
received anti-cancer therapy (e.g., immunotherapy, ADC) previously can be included
if their condition is stable without any medical intervention.
7. Patient has a history of CHF Class III/IV according to the NYHA Functional
Classification Appendix 2) or serious cardiac arrhythmias requiring treatment.
8. QTc interval (using Fridericia correction calculation) (QTcF) > 470 msec.
9. Current treatment with medication known to prolong the QT/QTcF interval or history
of additional risk factors for Torsade de Pointes (e.g., heart failure, Grade ≥ 3
hypokalemia, family history of long QT syndrome). Patient who has adequately
controlled condition or require use of medications from Table 28 may be allowed to
enroll upon agreement by the Investigator and Sponsor Medical Monitor.
10. Pregnant or lactating women.
11. 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 the
skin or cancer of the cervix in situ).
12. Malabsorption syndrome or other conditions (e.g., refractory nausea and vomiting,
external biliary diversion, or any significant small bowel resection) that may
interfere with adequate absorption of investigational product.
13. Uncontrolled intercurrent illness including, but not limited to, uncompensated
respiratory, cardiac, hepatic, or renal disease, active infection (including
untreated HIV and active clinical tuberculosis), symptomatic congestive heart
failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.
14. Current endocrinopathies, unless in the opinion of the Investigator, endocrine
complications are stable and well controlled and study participation does not
jeopardize patient's health and wellbeing. Patients with asymptomatic endocrine
disease on endocrine replacement therapy are eligible.
15. Active hepatitis B infection as defined by a positive HBsAg test and detectable HBV
DNA. Patients ineligible due to detectable levels of HBV DNA at baseline may be
rescreened for enrollment if their HBV DNA levels become undetectable after
treatment with antiviral agents, and upon agreement between the Investigator and
Sponsor Medical Monitor.
16. Active hepatitis C infection as defined by a reactive HCV antibody test and
detectable HCV RNA.
17. For patients with a history of HIV or AIDS:
1. Must have a CD4+ T-cell count ≥ 350 cells/μL.
2. Have not had an opportunistic infection within the previous 12 months.
3. To be on current ART regimen for a minimum of four weeks and have an HIV viral
load < 400 copies/mL at the time of enrollment.
4. Patients who are using concurrent strong CYP3A4 inhibitors (e.g., ritonavir,
cobicistat) or strong CYP3A4 inducers are excluded from the study if their
regimen cannot be altered. Otherwise, eligible study patients could be switched
to an alternate effective ART regimen before study participation.
18. Current treatment with a strong CYP3A4 inhibitor or inducer, Pgp inhibitor, or
CYP3A4 sensitive substrate as specifically listed in Table 26 and Table 27 within 14
days or five terminal half-lives prior to the first dose of study drug, whichever is
shorter.
19. Active bleeding disorders.
20. Prior solid organ transplantation.
21. Is, in the Investigator's opinion, unable or unwilling to comply with the study
procedures.
22. Have any condition or illness that, in the opinion of the Investigator, might
compromise patient safety or interfere with the evaluation of the safety of the
study drug.
