PARP Inhibitor CVL218 in Combination Therapy for Patients With Advanced Solid Tumors

NCT06078670 | Not Yet Recruiting Phase 1

• 1 other identifier: CVL218-1003
• Study Type: interventional
• Target: 96
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to evaluate the efficacy of CVL218 in combination with Toripalimab injection/Sintilimab injection (Darbersol, Sintilimab) in the treatment of advanced solid tumors. It focuses on assessing the safety, tolerability, and pharmacokinetic profile of a three-drug combination regimen comprising albumin-bound paclitaxel injection (Kealil), paclitaxel injection (Taxol), and Fuquinitinib capsule (Aiutec, Fruquintinib).

Conditions

Advanced Solid Tumor

Keywords

Triple negative breast cancer; stomach cancer; Intestinal cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicity (DLT) during the observation period of DLT

  The duration of DLT evaluation in Phase Ib is within the first cycle after dosing (within 21 days). Starting from the 500mg BID CVL218 dose group, each dose group was enrolled on the basis of 3 cases. If DLT was present in 2/3 or more of the group, one dose level should be lowered. If 1/3 of the subjects developed DLT, 3 more subjects were enrolled with the same dose. If 2/6 or more subjects develop DLT, the dose level should be lowered by one dose. After each dose group completes the DLT assessment, it is decided whether to move to the next dose group. The recommended dose (RP2D) will be determined based on the combined data of safety and tolerability, PK, pharmacodynamics, and initial anti-tumor efficacy of the drug obtained during the dose escalation phase. If dose-limiting toxicity (DLT) occurs in 0/3 subjects in a group, or in less than 2/6 subjects, the CVL218 dose can be used as the recommended dose.

  Incidence of dose-limiting toxicity (DLT) during the observation period of DLT，No more than six months；The interruption and reduction of drug dose in the cohorts of the combination regimen were studied，No more than three years

Secondary Outcomes (1)

• Duration of response (DoR), progression-free survival (PFS), disease control rate (DCR)as assessed by the RECIST v1.1

  Imaging evaluation was performed every 6 weeks (±7 days) for six months prior to treatment. After six months, they were evaluated every 12 weeks (±7 days). Tumor evaluation can be performed more frequently by the investigator according to clinical needs.

Study Arms (3)

Triple Negative Breast Cancer

EXPERIMENTAL

CVL218+Toripalimab+Paclitaxel For Injection (Albumin Bound)

Drug: CVL218

Stomach cancer

EXPERIMENTAL

CVL218+Sintilimab+Paclitaxel Injection

Drug: CVL218

Intestinal cancer

EXPERIMENTAL

CVL218+Sintilimab+Fruquintinib

Drug: CVL218

Interventions

CVL218 DRUG

Arm1: Triple negative breast cancer CVL218 is administered orally Triplelizumab injection was administered intravenously (IV) 240mg on D1 Paclitaxel injection (Kealil) 125mg /m2, D1, D8 administration Every 21 days for a drug cycle; Arm2: Gastric cancer CVL218 is administered orally Sindilizumab injection was given intravenously (IV) 200mg on D1 Paclitaxel injection (Taxol) 175mg /m2, D1 administration Every 21 days for a drug cycle; Arm3: Intestinal cancer CVL218 is administered orally Sindilizumab injection was given intravenously (IV) 200mg on D1 Fuquinitinib capsule 5mg QD orally, D1-14 administration Every 21 days is a medication cycle.

Also known as: Toripalimab、Paclitaxel For Injection (Albumin Bound)、Sintilimab、Paclitaxel Injection、Fruquintinib

Intestinal cancer; Stomach cancer; Triple Negative Breast Cancer

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients between the ages of 18 and 75 (including those aged 18 and 75, and those over 60 years old should not suffer from more than 3 complications of heart, lung, liver and kidney function at the same time), regardless of gender.
• \. Patients with locally advanced or metastatic advanced solid tumors confirmed by histology or cytology (including but not limited to triple-negative breast cancer, gastric cancer, colorectal cancer); Patients with ≤1 line of standard treatment failure (disease progression after treatment or intolerability of toxic side effects of treatment), or no standard treatment, or unable to receive standard treatment.
• \. In stage II, patients with positive PD-L1 molecular expression level combined with CPS≥1 were required to be enrolled, or there was evidence of harmful HRD gene variants (BRCA1, BRCA2, PALB2, ATM, CHEK2 variants, etc.).

You may not qualify if:

• Chemotherapy, radiotherapy, biotherapy and endocrinology were received within 4 weeks before the first administration
• Treatment, immunotherapy and other antitumor drugs, except the following:
• Nitrosourea or mitomycin C within 6 weeks before first use of the study drug;
• Oral fluorouracil and small molecule targeted drugs are used before first investigational drugs
• weeks or within 5 half-lives of the drug, whichever is longer;
• Traditional Chinese medicines with anti-tumor indications were used within 2 weeks before the first use of study drugs.
• \. Received other investigational drugs or treatments that are not on the market within 4 weeks prior to initial administration
• Therapy.
• \. Received major organ surgery (excluding puncture) within 4 weeks prior to initial administration
• Biopsy) or significant trauma.
• \. Received systemic glucocorticoids (strong) within 14 days prior to initial administration
• Pine \> 10mg/ day or equivalent dose of similar drugs) or other immunosuppressant
• Treatment;
• Except in the following cases: topical, ocular, intraarticular, intranasal, and inhalation
• Type I glucocorticoid therapy; Short-term use of corticosteroids for prophylactic treatment (eg to prevent contrast allergy).

Sponsors & Collaborators

• Fujian Cancer Hospital: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Stomach Neoplasms; Intestinal Neoplasms

Interventions

Injections

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: October 12, 2023
• Study Start: October 10, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 12, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share