CVL006 Combination Therapy in Advanced Solid Tumors

NCT07157956 | Not Yet Recruiting Phase 1

• 1 other identifier: CVL006-T1002
• Study Type: interventional
• Target: 318
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a multi-center, open-label, dose-escalation and dose-optimized phase I/II clinical trial. Objective: To determine the safety, tolerability, PK characteristics and preliminary efficacy data of CVL006 combined with pemetrexed + carboplatin/SKB264/ DS-8201a/ Enfortumab Vedotin in patients with advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor; DLT; RP2D

Outcome Measures

Primary Outcomes (3)

• DLT and RP2D of phase I

  DLT and RP2D of phase I (Arm1.1, Arm1.2, Arm1.3 and Arm1.4) CVL006 combined with pemetrexed + carboplatin/SKB264/ DS-8201a/ Enfortumab Vedotin in patients with advanced solid tumors

  28 days after the first medication; If the second administration is delayed, the DLT observation period will be extended to 14 days after the second administration

• Phase II, progression-free survival (PFS) according to RECISTv1.1 criteria

  The efficacy of phase II CVL006 combined with pemetrexed + carboplatin /SKB264/ DS-8201a/ Enfortumab Vedotin in the treatment of advanced solid tumors: progression-free survival (PFS) according to RECISTv1.1 criteria

  Imaging examinations should be conducted every 8 weeks (±7 days) after the initiation of administration

• Safety endpoints for phase I and Phase II

  Number of participants with adverse events (AE)/serious adverse events (SAE)

  From date of randomization until the date of first documented progression, assessed up to 36 months

Secondary Outcomes (6)

• Pharmacokinetic (PK) parameters of CVL006 in Phase I and Phase II

  From date of randomization until the date of first documented progression, assessed up to 36 months

• Pharmacokinetic (PK) parameters of CVL006 in Phase I and Phase II

  From date of randomization until the date of first documented progression, assessed up to 36 months

• Efficacy endpoints for Phase I and Phase II

  From date of randomization until the date of first documented progression, assessed up to 36 months

• Efficacy endpoints for Phase I and Phase II

  From date of randomization until the date of first documented progression, assessed up to 36 months

• ADA&Nab

  From date of randomization until the date of first documented progression, assessed up to 36 months

Study Arms (13)

Arm 1.1

EXPERIMENTAL

Patients with advanced solid tumors were enrolled in Arm1.1. The medication used was CVL006 combined with pemetrexed and carboplatin. Two dose groups were preset. The starting dose of CVL006 for DL1 was 10mg/kg (administered at Q2W or Q3W), and for DL2 (one dose higher than DL1). Pemetrexed + carboplatin was a fixed dose. Each dose group enrolled 3 to 6 patients, and Arm1.1 enrolled a total of 6 to 12 patients.

Drug: CVL006 combined with pemetrexed and carboplatin

Arm 1.2

EXPERIMENTAL

Patients with advanced solid tumors were enrolled in Arm1.2, and the medication used was CVL006 combined with SKB264. Two dose groups were preset. The starting dose of CVL006 for DL1 was 10mg/kg (administered at Q2W or Q3W), and for DL2 (one dose group higher than DL1). SKB264 was a fixed dose. Each dose group enrolled 3 to 6 patients, and Arm1.2 enrolled a total of 6 to 12 patients.

Drug: CVL006 in combination with SKB264

Arm 1.3

EXPERIMENTAL

Patients with advanced solid tumors were enrolled in Arm1.3, and the medication used was CVL006 combined with DS-8201a. Two dose groups were preset. The starting dose of CVL006 for DL1 was 10mg/kg (administered at Q2W or Q3W), and the dose for DL2 (one dose group higher than DL1). DS-8201a was a fixed dose. Each dose group enrolled 3 to 6 patients respectively, and Arm1.3 enrolled a total of 6 to 12 patients.

Drug: CVL006 in combination with DS-8201

Arm1.4

EXPERIMENTAL

Patients with advanced solid tumors were enrolled in Arm1.4 and treated with CVL006 combined with Enfortumab Vedotin. Two dose groups were preset. The starting dose of CVL006 for DL1 was 10mg/kg (administered at Q2W or Q3W), and the dose of DL2 (one dose group higher than DL1). Enfortumab Vedotin was a fixed dose. 3 to 6 patients were enrolled in each dose group, and 6 to 12 patients were enrolled in Arm1.4.

Drug: CVL006 in combination with Enfortumab Vedotin

Arm2.1

EXPERIMENTAL

NSCLC patients were enrolled in Arm2.1. The medication used was CVL006 combined with pemetrexed and carboplatin. 8 to 30 patients were enrolled.

Drug: CVL006 combined with pemetrexed and carboplatin

Arm2.2

EXPERIMENTAL

Patients with EGFRm nsqNSCLC were enrolled in Arm2.2. The medication used was CVL006 combined with pemetrexed and carboplatin. 8 to 30 patients were enrolled.

Drug: CVL006 combined with pemetrexed and carboplatin

Arm2.3

EXPERIMENTAL

Patients with malignant pleural mesothelioma were enrolled in Arm2.3. The medication used was CVL006 combined with pemetrexed and carboplatin. 8 to 30 patients were enrolled.

Drug: CVL006 combined with pemetrexed and carboplatin

Arm2.4

EXPERIMENTAL

Breast cancer patients were enrolled in Arm2.4, and the medication used was CVL006 combined with SKB264. 8 to 30 patients were enrolled.

Drug: CVL006 in combination with SKB264

Arm2.5

EXPERIMENTAL

Patients with EGFRm nsqNSCLC were enrolled under Arm2.5, with the medication being CVL006 combined with SKB264. 8 to 30 patients were enrolled.

Drug: CVL006 in combination with SKB264

Arm2.6

EXPERIMENTAL

Breast cancer patients were enrolled in Arm2.6, and the medication used was CVL006 combined with DS-8201a. 8 to 30 patients were enrolled.

Drug: CVL006 in combination with DS-8201

Arm2.7

EXPERIMENTAL

NSCLC patients were enrolled in Arm2.7. The medication used was CVL006 combined with DS-8201a. 8 to 30 patients were enrolled.

Drug: CVL006 in combination with DS-8201

Arm2.8

EXPERIMENTAL

Patients with adenocarcinoma of the stomach or gastroesophageal junction were enrolled under Arm2.8. The medication used was CVL006 combined with DS-8201a. 8 to 30 patients were enrolled.

Drug: CVL006 in combination with DS-8201

Arm2.9

EXPERIMENTAL

Patients with urothelial carcinoma were enrolled under Arm2.9. The medication used was CVL006 combined with Enfortumab Vedotin. 8t to 30 patients were enrolled.

Drug: CVL006 in combination with Enfortumab Vedotin

Interventions

CVL006 combined with pemetrexed and carboplatin DRUG

CVL006 combined with pemetrexed and carboplatin

Also known as: CVL006（B006 Injection）、pemetrexed（Pemetrexed Disodium for Injection）、carboplatin（Carboplatin Injection）

Arm 1.1; Arm2.1; Arm2.2; Arm2.3

CVL006 in combination with SKB264 DRUG

CVL006 in combination with SKB264

Also known as: CVL006（B006 Injection）、SKB264（Sacituzumab tirumotecan）

Arm 1.2; Arm2.4; Arm2.5

CVL006 in combination with DS-8201 DRUG

CVL006 in combination with DS-8201

Also known as: CVL006（B006 Injection）、DS-8201a（Trastuzumab deruxtecan）

Arm 1.3; Arm2.6; Arm2.7; Arm2.8

CVL006 in combination with Enfortumab Vedotin DRUG

CVL006 in combination with Enfortumab Vedotin

Also known as: CVL006（B006 Injection）、Enfortumab Vedotin（Padcev）

Arm1.4; Arm2.9

Eligibility Criteria

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

You may qualify if:

• Age: 18 to 75 years old (including both ends), gender not limited;
• Stage I Arm1.1, Arm1.2, Arm1.3 and Arm1.4: Locally advanced, recurrent or metastatic solid tumors confirmed by histology or cytology, with previous treatment failure.
• Phase II Arm2.1, Arm2.2, Arm2.5 and Arm2.7: For NSCLC Arm2.1: Non-squamous, wild-type NSCLC Arm2.2: EGFRm nsqNSCLC Arm2.3: Malignant pleural mesothelioma Arm2.4: triple-negative breast cancer Arm2.5: EGFRm nsqNSCLC Arm2.6: breast cancer Arm2.7: NSCLC Arm2.8: adenocarcinoma of the stomach or gastroesophageal junction Arm2.9: urothelial carcinoma
• All subjects must provide tumor tissue samples for PD-L1 testing: Tumor tissue samples should preferably be newly obtained tumor tissues. For subjects who cannot provide newly obtained tissues, tumor tissue samples archived within 3 years prior to the first study treatment can be provided. The sample type should be neutral formalin-fixed and paraffin-embedded \[FFPE\] tissue wax blocks or at least 6 unstained tumor tissue sections. If the number is less than 6 pieces, it is necessary to negotiate with the sponsor and only allow enrollment after obtaining consent.
• ECOG overall performance status (PS) 0-1 point;
• Predicted survival period ≥ 3 months;
• According to the efficacy evaluation criteria for solid tumors (RECISTv 1.1), there is at least one measurable lesion;
• Have sufficient bone marrow and organ function (no blood components and/or cell growth factors have been used within 14 days prior to the start of the study treatment) :
• Hemoglobin (HB) ≥ 90 g/L;
• Neutrophil count (ANC) ≥1.5×109/L;
• Platelet count (PLT) ≥ 90×109/L;
• Total bilirubin \< 1.5×ULN (for subjects diagnosed with Gilbert syndrome, total bilirubin ≤ 3×ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN (for patients with liver metastasis, ALT and/or AST≤ 5×ULN);
• Serum creatinine ≤ 1.5×ULN or creatinine clearance ≥ 60 mL/min (calculated according to the Cockcroft-Gault formula);
• International normalized ratio (INR) and activated partial thromboplastin (APTT) time ≤1.5×ULN;

You may not qualify if:

• Accompanied by untreated or active central nervous system (CNS) tumor metastasis. Subjects with a history of meningeal metastasis or those currently having meningeal metastasis.
• Patients with other malignant tumors, excluding fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection, ductal carcinoma in situ after radical resection, papillary thyroid carcinoma after radical resection, or those with other malignant tumors, must have at least a 3-year tumor-free period.
• For those whose tumor lesions are judged by researchers to have a bleeding tendency, such as those whose imaging examinations during the screening period show that the subjects have: imaging evidence of tumor invasion or encirclement of large blood vessels;
• Exclude subjects who have previously used VEGF/PD-1 (PD-L1) bispecific antibodies; Subjects who have previously received targeted therapy with TROP2, HER2 or Nectin-4, ADC, or any study drugs containing MMAE and whose treatment duration is less than 6 months should also be excluded. Subjects who had previously used bevacizumab were excluded.
• Previously used immune checkpoint agonist therapy (such as CD137 agonists), anti-CD73 inhibitors, immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), and immune cell therapy (such as CAR-T) And other treatments targeting the tumor immune mechanism are not allowed to be enrolled.
• It is known that there is an allergic reaction to CVL006, SKB264, T-DXd, Enfortumab Vedotin, pemetrexel or platinum-based or any excipient component of the study drug (including histidine, trehalose and polysorbide 20), or there is a history of severe allergic reaction to other monoclonal antibodies;
• Have serious cardiovascular and cerebrovascular diseases, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities within 6 months prior to the first use of the study drug, such as ventricular arrhythmias requiring clinical intervention, II-III degree atrioventricular block, etc.
• Acute coronary syndrome, congestive heart failure (New York Heart Association (NYHA) cardiac function classification ≥ grade II), and aortic dissection occurred within 6 months prior to the first use of the study drug;
• There have been arteriovenous thrombotic events such as cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, stroke), deep vein thrombosis and pulmonary embolism, etc. within 6 months before the first use of the study drug;
• The left ventricular ejection fraction (LVEF) was less than 50% within 28 days prior to the first use of the study drug;
• The mean value of QTcF obtained from three electrocardiogram examinations at baseline 12 (or above) in the resting state, with QTcF\> 470 ms (for females) or QTcF\> 450 ms (for males);
• There is uncontrollable pleural effusion, peritoneal effusion or pericardial effusion;
• Patients with known or suspected interstitial pneumonia; Within three months prior to the first administration, there are other severe pulmonary diseases that seriously affect respiratory function, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/obliterative bronchiolitis; Non-infectious pulmonary inflammation that currently requires steroid treatment;
• Patients who have previously received immunotherapy and have developed grade ≥3 irAE or grade ≥2 immune-related myocarditis;

Sponsors & Collaborators

• Convalife (Shanghai) Co., Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Interventions

Pemetrexed; Carboplatin; trastuzumab deruxtecan; enfortumab vedotin

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Officials

• Li Zhang

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dong Wang

CONTACT

18064082990; dong.wang@convalife.com

Qiong Wang

CONTACT

18062000521; qiong.wang@convalife.com

Study Design

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

Model Details: This study is a multi-center, open-label, dose-escalation and dose-optimized phase I/II clinical trial. Objective: To determine the safety, tolerability, PK characteristics and preliminary efficacy data of CVL006 combined with pemetrexed + carboplatin/SKB264/ DS-8201a/ Enfortumab Vedotin in patients with advanced solid tumors.

Study Record Dates

• First Submitted: August 22, 2025
• First Posted: September 5, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): August 12, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)