Advanced Solid Tumor, Breast Neoplasms, Cancer, Lung Cancer, Metastatic Solid Tumor, Neuroendocrine Carcinoma, Neuroendocrine Tumors, RB1 Gene Mutation, Refractory Solid Tumor, Triple Negative Breast Cancer
Conditions
Keywords
Phase 1, CID-078, Estrogen
Brief summary
This is a first-in-human, multicenter, open-label, phase 1 study to evaluate safety, tolerability, and efficacy of CID-078, a Cyclin A/B-RxL inhibitor, in patients with advanced solid tumors.
Detailed description
This is a first-in-human, multicenter, open-label, phase 1 study to evaluate safety, tolerability, and efficacy of CID-078, a Cyclin A/B-RxL (Arginine-any amino acid-lysine) inhibitor, in patients with advanced solid tumors. The study will be conducted at approximately 20 centers. CID-078 will be evaluated as an oral therapeutic. This study is divided into three parts: Part 1a Dose Escalation, Part 1b New Formulation Dose Escalation/Pilot Food Effect and Part 2 Dose Expansion. Part 1a will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of CID-078, and identify recommended dose for expansion (RDE) of CID-078 using a Backfill Bayesian Optimal Interval design. Dose escalation will occur sequentially over several dose levels. Part 1b will evaluate the safety and tolerability of a new CID-078 oral formulation, investigate the pharmacokinetic exposure between the original and new CID-078 formulations, and evaluate the effect of food on CID-078 pharmacokinetics. Part 1b will be initiated upon availability of the new CID-078 oral formulation. Part 2 is a Dose Expansion. Upon identification of the RDE as determined by the SRC, CID-078 will be further evaluated for it's antitumor activity/efficacy along with characterization of it's safety, tolerability, pharmacokinetics, and pharmacodynamics in three tumor specific cohorts: TNBC, SCLC, and solid tumors harboring a RB1 alteration or Rb protein LoF; with an additional possible cohort expansion of N=20 for either TNBC or RB1-altered solid tumor cohort based on data observed. The study consists of a 28-day Screening Period, a Treatment Period, an End of Treatment (EOT) Visit, and a Safety Follow-up Visit. After confirming eligibility, patients enter the Treatment Period that consists of repeating 21-day treatment cycles. Study drug treatment cycles will continue for as long as the patient does not meet study drug discontinuation criteria. Within 7 days of the last dose of study drug or the decision to withdraw from the study, patients will undergo an EOT visit and a Safety Follow-Up visit 28 days after the EOT visit.
Interventions
DRUGCID-078 Monotherapy
Cyclin A/B-RxL inhibitor, twice-a-day in repeating 21-day treatment cycles until disease progression or discontinuation criteria.
Sponsors
Circle Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 and Part 1b Backfill: patients with TNBC, SCLC, and solid tumors harboring a RB1 or CDKN2A/B loss genomic alteration or Rb protein LoF. Additional tumor types or genomic alterations may be considered by the SRC as data become available. 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 if medically feasible. 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), or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 based alternative methods of determination (e.g., modification of diet in renal disease \[MDRD\], 24-hour urine collection) if consistent with local or 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Incidence of Treatment Emergent Adverse Events (TEAEs) based on CTCAE v5.0. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. | — |
| Part 1: Incidence of Treatment Related Adverse Events (TRAEs) based on CTCAE v5.0. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. | — |
| Part 1: Incidence of Dose-Limiting Toxicities (DLTs). | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to end of cycle 1, up to 21 + 4 days. | — |
| Part 1: To determine recommended dose(s) for expansion (RDEs) for evaluation for Part 2. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. | The RDEs will be determined using all available information, including, but not limited to, AEs, dose-limiting toxicities, pharmacokinetic parameters, clinical laboratory tests, and efficacy measures observed in Part 1 Dose Escalation. |
| Part 2: Percentage of patients with confirmed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria in Solid Tumors. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. | — |
| Part 2: Duration of confirmed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria in Solid Tumors. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. | — |
| Part 2: Duration of disease progression free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria in Solid Tumors. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. | — |
| Part 2: To determine Provisional Recommended Phase 2 Dose (RP2D) for future dose optimization. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. | Provisional RP2D will be determined using all available information, including, but not limited to, Adverse Events (AEs), dose-limiting toxicities, pharmacokinetic parameters, clinical laboratory tests, and efficacy measures observed during the study. |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: Percentage of patients with confirmed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria in Solid Tumors. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
| Part 1: Duration of confirmed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria in Solid Tumors. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
| Part 1: Duration of disease progression free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria in Solid Tumors. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
| Part 1: Maximum plasma concentration (Cmax) of CID-078 in fasted and fed state. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
| Part 1: Time to maximum plasma concentration (Tmax) of CID-078 in fasted and fed state. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
| Part 1: Area under the concentration-time curve (AUC) of CID-078 in fasted and fed state. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
| Part 1 and Part 2: Terminal half-life (t1/2) of CID-078 in fasted and fed state. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
| Part 2: Incidence of Treatment Emergent Adverse Events (TEAEs) based on CTCAE v5.0. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
| Part 2: Incidence of Treatment Related Adverse Events (TRAEs) based on CTCAE v5.0. | From first dose of CID-078 on Cycle 0 Day 1/ Cycle 1 Day 1 (each cycle is 21 days) to 28 days after the last dose of study drug. |
Countries
United States
Outcome results
None listed