A Phase I Study of CG-7321 Monotherapy or Combination Therapy in Advanced Solid Tumors
A Phase I, Open-Label, Multi-Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CG-7321 as Monotherapy or in Combination Therapy in Subjects With Advanced Solid Tumors
This is a Phase I, open-label, multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of CG-7321 capsules as monotherapy or in combination with fulvestrant in subjects with advanced solid tumors.
The study consists of:
- Part Ia (Monotherapy): Dose escalation (accelerated titration followed by 3+3 design) from 2mg to 50mg twice daily (BID), plus dose expansion cohorts in advanced solid tumors including HR+/HER2- breast cancer, ovarian cancer, gastric cancer, and other tumor types.
- Part Ib (Combination Therapy): Dose escalation of CG-7321 combined with fulvestrant in HR+/HER2- advanced breast cancer.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
CG-7321 is a novel oral small molecule inhibitor of cyclin-dependent kinases (CDKs), being developed for the treatment of advanced solid tumors. Preclinical studies have demonstrated potent anti-tumor activity in breast cancer, ovarian cancer, and gastric cancer models.
This Phase I study employs a dose escalation design to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of CG-7321.
Part Ia evaluates CG-7321 monotherapy with dose levels of 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, and 50mg BID in a 28-day cycle. Single dosing (Cycle 0) followed by multiple dosing (Cycle 1 onwards) will be evaluated.
Part Ib evaluates CG-7321 in combination with fulvestrant in HR+/HER2- advanced breast cancer patients.
Dose expansion cohorts will further evaluate safety, PK, and preliminary efficacy at or near the RP2D in specific tumor types.
Eligible subjects include patients with histologically/cytologically confirmed advanced or metastatic solid tumors who have failed, are intolerant to, or have no effective standard therapy available, or who refuse standard treatment.
The Part Ia (monotherapy dose escalation) will be conducted first.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Fase 1
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: Ke Lan
- Telefonnummer: +86-13982078904
- E-mail: lanke@cynogen.com
Studiesteder
-
-
Fujian
-
Fuzhou, Fujian, Kina, 350014
- Rekruttering
- Fujian Cancer Hospital
-
Ledende efterforsker:
- Fan Wu, MD
-
Kontakt:
- Jin Tan
- Telefonnummer: +86-18180770362
- E-mail: tanjin@cynogen.com
-
-
Liaoning
-
Dalian, Liaoning, Kina, 116000
- Rekruttering
- Zhongshan Hospital of Dalian University
-
Kontakt:
- Jin Tan
- Telefonnummer: +86-18180770362
- E-mail: tanjin@cynogen.com
-
Ledende efterforsker:
- Xiang Li, MD
-
Ledende efterforsker:
- Ruoyu Wang, MD
-
-
Shanghai Municipality
-
Shanghai, Shanghai Municipality, Kina, 200032
- Rekruttering
- Fudan University Shanghai Cancer Center
-
Ledende efterforsker:
- Jian Zhang, MD
-
Kontakt:
- Jin Tan
- Telefonnummer: +86-18180770362
- E-mail: tanjin@cynogen.com
-
-
Sichuan
-
Chengdu, Sichuan, Kina, 610041
- Rekruttering
- West China Hospital, Sichuan University
-
Kontakt:
- Jin Tan
- Telefonnummer: +86-18180770362
- E-mail: tanjin@cynogen.com
-
Ledende efterforsker:
- Ting Luo, MD
-
Ledende efterforsker:
- Ping Feng, MD
-
-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- 1. Voluntary signed informed consent and compliance with protocol requirements
- 2. Age ≥18 years, any gender
- 3. Life expectancy ≥12 weeks
- 4. Eastern Cooperative Oncology Group(ECOG) performance status 0-1
- 5. For Ia monotherapy dose escalation: patients with cytologically and/or histopathologically confirmed advanced or metastatic solid tumors who have failed, are intolerant to, or have no effective standard treatment, or who refuse standard treatment
- 6. Voluntary provision of tumor tissue specimens (archived within 2 years or fresh tissue)
- 7. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1(RECIST 1.1)
- 8. Prior anticancer treatment-related toxicities resolved to ≤1 grade (except alopecia)
- 9. Adequate organ and bone marrow function
- 10. Negative serum pregnancy test within 7 days before first dose
- 11. Agreement to use effective contraception from ICF signing to ≥6 months after last dose
- 12. No breastfeeding during study and ≥6 months after last dose
- 13. Understanding of study and voluntary written informed consent
Exclusion Criteria:
- 1. Anticancer therapy (chemotherapy, targeted therapy, biologics, immunotherapy, radiotherapy) within 4 weeks before first dose, or participation in other interventional clinical studies (observational studies excluded)
- 2. Strong Cytochrome P450 3A4(CYP3A4)inhibitors within 2 weeks before first dose
- 3. Strong Cytochrome P450 2C8(CYP2C8) inhibitors within 2 weeks before first dose
- 4. Other active malignancies within 3 years before first dose (except curable tumors treated radically)
- 5. Primary Central Nervous System(CNS) tumors or CNS metastases that failed local treatment (stable asymptomatic CNS metastases allowed)
- 6. Conditions affecting drug absorption or Pharmacokinetics(PK) parameters (e.g., uncontrolled nausea/vomiting, chronic diarrhea, malabsorption syndrome)
- 7. Uncontrolled or significant cardiovascular disease,
- 8. Active infection requiring systemic therapy within 2 weeks;
- 9. Major surgery within 4 weeks before first dose (except minor procedures)
- 10. Known allergy to study drug or excipients
- 11. Mental or cognitive impairment affecting study compliance
- 12. Known alcohol or drug dependence
- 13. Pregnant or lactating women
- 14. Investigator deems subject unsuitable for study participation
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: CG-7321 2mg BID
CG-7321 capsule 2mg, orally twice daily, 28-day cycle. Cycle 0: Single dose on Day 1. Cycle 1 onwards: Continuous dosing. |
Novel oral cyclin-dependent kinase (CDK) inhibitor. Dose levels: 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, 50mg BID. 28-day cycle. |
|
Eksperimentel: CG-7321 6mg BID
CG-7321 capsule 6mg, orally twice daily, 28-day cycle. Cycle 0: Single dose on Day 1. Cycle 1 onwards: Continuous dosing. |
Novel oral cyclin-dependent kinase (CDK) inhibitor. Dose levels: 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, 50mg BID. 28-day cycle. |
|
Eksperimentel: CG-7321 12mg BID
CG-7321 capsule 12mg, orally twice daily, 28-day cycle. Cycle 0: Single dose on Day 1. Cycle 1 onwards: Continuous dosing. |
Novel oral cyclin-dependent kinase (CDK) inhibitor. Dose levels: 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, 50mg BID. 28-day cycle. |
|
Eksperimentel: CG-7321 20mg BID
CG-7321 capsule 20mg, orally twice daily, 28-day cycle. Cycle 0: Single dose on Day 1. Cycle 1 onwards: Continuous dosing. |
Novel oral cyclin-dependent kinase (CDK) inhibitor. Dose levels: 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, 50mg BID. 28-day cycle. |
|
Eksperimentel: CG-7321 30mg BID
CG-7321 capsule 30mg, orally twice daily, 28-day cycle. Cycle 0: Single dose on Day 1. Cycle 1 onwards: Continuous dosing. |
Novel oral cyclin-dependent kinase (CDK) inhibitor. Dose levels: 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, 50mg BID. 28-day cycle. |
|
Eksperimentel: CG-7321 40mg BID
CG-7321 capsule 40mg, orally twice daily, 28-day cycle. Cycle 0: Single dose on Day 1. Cycle 1 onwards: Continuous dosing. |
Novel oral cyclin-dependent kinase (CDK) inhibitor. Dose levels: 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, 50mg BID. 28-day cycle. |
|
Eksperimentel: CG-7321 50mg BID
CG-7321 capsule 50mg, orally twice daily, 28-day cycle. Cycle 0: Single dose on Day 1. Cycle 1 onwards: Continuous dosing. |
Novel oral cyclin-dependent kinase (CDK) inhibitor. Dose levels: 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, 50mg BID. 28-day cycle. |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Dose-Limiting Toxicities (DLTs)
Tidsramme: DLT observation period [approximately 28 days]
|
Number of participants experiencing DLTs during DLT evaluation period. |
DLT observation period [approximately 28 days]
|
|
Maximum Tolerated Dose (MTD)
Tidsramme: End of dose escalation phase [approximately 6-12 months]
|
The highest dose level at which ≤2/6 evaluable subjects experience DLT. |
End of dose escalation phase [approximately 6-12 months]
|
|
Recommended Phase 2 Dose (RP2D)
Tidsramme: End of dose escalation phase [approximately 6-12 months]
|
The dose level recommended for Phase 2 studies. |
End of dose escalation phase [approximately 6-12 months]
|
|
Adverse Events (AEs) and SAEs
Tidsramme: From first dose to 30 days after last dose [up to approximately 2 years]
|
Incidence and severity of AEs and SAEs, graded per NCI-CTCAE Version 5.0. |
From first dose to 30 days after last dose [up to approximately 2 years]
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Objective Response Rate (ORR)
Tidsramme: Every 8 weeks [up to approximately 2 years]
|
Percentage achieving CR or PR per RECIST v1.1. |
Every 8 weeks [up to approximately 2 years]
|
|
Disease Control Rate (DCR)
Tidsramme: Every 8 weeks [up to approximately 2 years]
|
Percentage achieving CR, PR, or SD per RECIST v1.1. |
Every 8 weeks [up to approximately 2 years]
|
|
Duration of Response (DoR)
Tidsramme: From first documented response until disease progression or death [up to approximately 2 years]
|
Time from first documented response to disease progression or death. |
From first documented response until disease progression or death [up to approximately 2 years]
|
|
Progression-Free Survival (PFS)
Tidsramme: From first dose until disease progression or death [up to approximately 2 years]
|
Time from first dose to disease progression per RECIST v1.1 or death. |
From first dose until disease progression or death [up to approximately 2 years]
|
|
Overall Survival (OS)
Tidsramme: From first dose until death [up to approximately 5 years]
|
Time from first dose to death from any cause. |
From first dose until death [up to approximately 5 years]
|
|
Observed plasma maximum concentration (Cmax) of CG-7321 and its metabolite
Tidsramme: Cycle 0 Day 1, Cycle 1 Day 1 up to Cycle 6 Day 1 (each cycle is 28 days)
|
Cycle 0 Day 1, Cycle 1 Day 1 up to Cycle 6 Day 1 (each cycle is 28 days)
|
|
|
Area under the concentration-time curve (AUC) of CG-7321 and its metabolite
Tidsramme: Cycle 0 Day 1, Cycle 1 Day 1 up to Cycle 6 Day 1 (each cycle is 28 days)
|
Cycle 0 Day 1, Cycle 1 Day 1 up to Cycle 6 Day 1 (each cycle is 28 days)
|
|
|
Half-life (T1/2) of CG-7321 and its metabolite
Tidsramme: Cycle 0 Day 1, Cycle 1 Day 1 up to Cycle 6 Day 1 (each cycle is 28 days)
|
Cycle 0 Day 1, Cycle 1 Day 1 up to Cycle 6 Day 1 (each cycle is 28 days)
|
|
|
Time to maximum concentration(Tmax) of CG-7321 and its metabolite
Tidsramme: Cycle 0 Day 1, Cycle 1 Day 1 up to Cycle 6 Day 1 (each cycle is 28 days)
|
Cycle 0 Day 1, Cycle 1 Day 1 up to Cycle 6 Day 1 (each cycle is 28 days)
|
Andre resultatmål
Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Biomarkers
Tidsramme: Baseline and during treatment as tissue samples become available [up to approximately 2 years]
|
Exploratory biomarker analysis including but not limited to CCNE expression levels. |
Baseline and during treatment as tissue samples become available [up to approximately 2 years]
|
|
Tumor-to-blood drug concentration ratio
Tidsramme: At time of tumor biopsy during treatment [up to approximately 2 years]
|
Ratio of CG-7321 and CG1-Mp2 concentrations in tumor tissue versus peripheral blood. |
At time of tumor biopsy during treatment [up to approximately 2 years]
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Urogenitale sygdomme
- Genitale sygdomme
- Sygdomme i det endokrine system
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Neoplasmer
- Urogenitale sygdomme hos kvinder
- Kvinders urogenitale sygdomme og graviditetskomplikationer
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Sygdomme i fordøjelsessystemet
- Gastrointestinale sygdomme
- Mavesygdomme
- Kønssygdomme, kvindelige
- Neoplasmer i endokrine kirtler
- Ovariesygdomme
- Adnexale sygdomme
- Genitale neoplasmer, kvindelige
- Gonadale lidelser
- Hudsygdomme
- Brystsygdomme
- Hud- og bindevævssygdomme
- Neoplasmer i maven
- Ovariale neoplasmer
- Brystneoplasmer
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- CG-7321-001
- CTR20240687/CTR20254836 (Registry Identifier: ChinaDrugTrials)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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