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The Study of Tusamitamab Ravtansine (IBI126) Combined With Sintilimab and Tusamitamab Ravtansine (IBI126) Combined With Sintilimab Plus Platinum-based Chemotherapy and Pemetrexed in Subjects With CEACAM5 Positive Expression Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)

Primary Purpose

Non-squamous Non-small-cell Lung Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tusamitamab ravtansine+Sintilimab+Carboplatin or Cisplatin+Pemetrexed
Sintilimab+Carboplatin or Cisplatin+Pemetrexed
Tusamitamab ravtansine+Sintilimab
Sponsored by
Innovent Biologics (Suzhou) Co. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-squamous Non-small-cell Lung Cancer focused on measuring CEACAM5

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria apply: I1. Age ≥ 18 years and < 75 years males of females. I2. Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation, BRAF mutation or ALK/ROS alterations. I3. No prior systemic therapy for the treatment of advanced or metastatic disease. I4. Expression of CEACAM5 as demonstrated prospectively by a centrally assessed IHC assay with ≥ 2+ in intensity involving at least 1% of the tumor cell population in archival tumor sample (or if not, available fresh biopsy sample will be collected if considered an acceptable risk by the treating physician). I5. Adequate hematologic/liver/renal/coagulation function. I6. Life expectancy exceeds 3 months. I7. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Exclusion criteria: E1. Hstologically or cytologically confirmed mixed NSCLC with small-cell or prodominant squamous carcinoma components. E2. Unstable brain metastases and history of leptomeningeal disease. E3. Significant concomitant illness, including any severe medical conditions that, in the opinion of the investigator or sponsor, would impair the subject's participation in the study or interpretation of the results. E4. History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment. E5. History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B (defined as either positive HBsAg or positive hepatitis B viral DNA test above the lower limit of detection of the assay), or C (defined as a known positive hepatitis C antibody result and known quantitative HCV RNA results greater than the lower limits of detection of the assay) infection. E6. History of active autoimmune disease that has required systemic treatment in the past 2 years. E7. Non-resolution of any prior treatment-related toxicity to < Grade 2 according to NCI CTCAE V5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone-replacement therapy. E8. Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. The use of contact lenses is not permitted. Patients using contact lenses who are not willing to stop wearing them for the duration of the study intervention are excluded. E9. Received traditional Chinese medicine with anti-tumor indications within 2 weeks prior the first administration, or received immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use for pleural effusion control) within 2 weeks prior administration. E10. Have received prior systemic therapy for advanced/metastatic NSCLC.

Sites / Locations

  • Zhejiang Cancer Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

tusamitamab ravtansine + sintilimab

Tusamitamab ravtansine + Sintilimab + carboplatin/ cisplatin + pemetrexed

Sintilimab + carboplatin/ cisplatin + pemetrexed

Arm Description

Sintilimab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.

Sintilimab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin / cisplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.

Pemetrexed will be infused over 10 minutes after Sintilimab infusion on Day 1 and then Q3W. Carboplatin/ cisplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR) per RECIST 1.1 by investigators.
ORR is defined as proportion of participants who have a confirmed complete

Secondary Outcome Measures

Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities
TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
Pharmacokinetic concentrations of tusamitamab ravtansine (IBI126)
Duration of Response (DoR)
DoR is defined the time when subject reaches complete or partial response for the first time to the progression of the disease.
Progression-free Survival (PFS)
Time to Response (TTR)
Disease Control Rate (DCR)

Full Information

First Posted
April 17, 2023
Last Updated
May 5, 2023
Sponsor
Innovent Biologics (Suzhou) Co. Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05849246
Brief Title
The Study of Tusamitamab Ravtansine (IBI126) Combined With Sintilimab and Tusamitamab Ravtansine (IBI126) Combined With Sintilimab Plus Platinum-based Chemotherapy and Pemetrexed in Subjects With CEACAM5 Positive Expression Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Official Title
Open-label, Phase 2 Study of Tusamitamab Ravtansine (IBI126) Combined With Sintilimab and Tusamitamab Ravtansine (IBI126) Combined With Sintilimab Plus Platinum-based Chemotherapy and Pemetrexed in Subjects With CEACAM5 Positive Expression Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 30, 2023 (Anticipated)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innovent Biologics (Suzhou) Co. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Primary objective: ·To assess the antitumor activity of tusamitamab ravtansine in combination with sintilimab and tusamitamab ravtansine in combination with sintilimab, platinum-based chemotherapy and pemetrexed in the NSQ NSCLC population. Secondary objectives: To assess the safety and tolerability of tusamitamab ravtansine in combination with sintilimab and tusamitamab ravtansine in combination with sintilimab, platinum-based chemotherapy and pemetrexed in the NSQ NSCLC population. To assess the pharmacokinetic (PK) characteristic of tusamitamab ravtansine in combination with sintilimab and tusamitamab ravtansine in combination with sintilimab, platinum-based chemotherapy and pemetrexed in the NSQ NSCLC population.
Detailed Description
The expected duration of the study intervention for participants may vary based on progression date; median expected duration of study per participant is estimated 10 months (up to 1 month for screening, a median of 6 months for treatment, and a median of 3 months for end-of-treatment assessments and safety follow-up visit).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-squamous Non-small-cell Lung Cancer
Keywords
CEACAM5

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
tusamitamab ravtansine + sintilimab
Arm Type
Experimental
Arm Description
Sintilimab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.
Arm Title
Tusamitamab ravtansine + Sintilimab + carboplatin/ cisplatin + pemetrexed
Arm Type
Experimental
Arm Description
Sintilimab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin / cisplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
Arm Title
Sintilimab + carboplatin/ cisplatin + pemetrexed
Arm Type
Placebo Comparator
Arm Description
Pemetrexed will be infused over 10 minutes after Sintilimab infusion on Day 1 and then Q3W. Carboplatin/ cisplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
Intervention Type
Drug
Intervention Name(s)
Tusamitamab ravtansine+Sintilimab+Carboplatin or Cisplatin+Pemetrexed
Intervention Description
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous. Other Name: Tusamitamab ravtansine. Other Name: Tyvyt®
Intervention Type
Drug
Intervention Name(s)
Sintilimab+Carboplatin or Cisplatin+Pemetrexed
Intervention Description
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Tusamitamab ravtansine+Sintilimab
Intervention Description
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous. Other Name: Tusamitamab ravtansine. Other Name: Tyvyt®
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) per RECIST 1.1 by investigators.
Description
ORR is defined as proportion of participants who have a confirmed complete
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities
Description
TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame
3 years
Title
Pharmacokinetic concentrations of tusamitamab ravtansine (IBI126)
Time Frame
3 years
Title
Duration of Response (DoR)
Description
DoR is defined the time when subject reaches complete or partial response for the first time to the progression of the disease.
Time Frame
3 years
Title
Progression-free Survival (PFS)
Time Frame
3 years
Title
Time to Response (TTR)
Time Frame
3 years
Title
Disease Control Rate (DCR)
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria apply: I1. Age ≥ 18 years and < 75 years males of females. I2. Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation, BRAF mutation or ALK/ROS alterations. I3. No prior systemic therapy for the treatment of advanced or metastatic disease. I4. Expression of CEACAM5 as demonstrated prospectively by a centrally assessed IHC assay with ≥ 2+ in intensity involving at least 1% of the tumor cell population in archival tumor sample (or if not, available fresh biopsy sample will be collected if considered an acceptable risk by the treating physician). I5. Adequate hematologic/liver/renal/coagulation function. I6. Life expectancy exceeds 3 months. I7. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Exclusion criteria: E1. Hstologically or cytologically confirmed mixed NSCLC with small-cell or prodominant squamous carcinoma components. E2. Unstable brain metastases and history of leptomeningeal disease. E3. Significant concomitant illness, including any severe medical conditions that, in the opinion of the investigator or sponsor, would impair the subject's participation in the study or interpretation of the results. E4. History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment. E5. History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B (defined as either positive HBsAg or positive hepatitis B viral DNA test above the lower limit of detection of the assay), or C (defined as a known positive hepatitis C antibody result and known quantitative HCV RNA results greater than the lower limits of detection of the assay) infection. E6. History of active autoimmune disease that has required systemic treatment in the past 2 years. E7. Non-resolution of any prior treatment-related toxicity to < Grade 2 according to NCI CTCAE V5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone-replacement therapy. E8. Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. The use of contact lenses is not permitted. Patients using contact lenses who are not willing to stop wearing them for the duration of the study intervention are excluded. E9. Received traditional Chinese medicine with anti-tumor indications within 2 weeks prior the first administration, or received immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use for pleural effusion control) within 2 weeks prior administration. E10. Have received prior systemic therapy for advanced/metastatic NSCLC.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yun Fan
Phone
0571-88122482
Email
fanyun@zjcc.org.cn
Facility Information:
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Feiyan Li
Phone
0571-88122146
Email
irb@zjcc.org.cn

12. IPD Sharing Statement

Learn more about this trial

The Study of Tusamitamab Ravtansine (IBI126) Combined With Sintilimab and Tusamitamab Ravtansine (IBI126) Combined With Sintilimab Plus Platinum-based Chemotherapy and Pemetrexed in Subjects With CEACAM5 Positive Expression Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)

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