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)

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-squamous Non-small-cell Lung Cancer
• Intervention / Treatment: Drug: Tusamitamab ravtansine+Sintilimab; Drug: Tusamitamab ravtansine+Sintilimab+Carboplatin or Cisplatin+Pemetrexed; Drug: Sintilimab+Carboplatin or Cisplatin+Pemetrexed

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).

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yun Fan; Phone Number: 0571-88122482; Email: fanyun@zjcc.org.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
      • Contact: Feiyan Li; Phone Number: 0571-88122146; Email: irb@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tusamitamab ravtansine + sintilimab; Sintilimab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.	Drug: Tusamitamab ravtansine+Sintilimab; Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous. Other Name: Tusamitamab ravtansine. Other Name: Tyvyt®
Experimental: Tusamitamab ravtansine + Sintilimab + carboplatin/ cisplatin + pemetrexed; 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.	Drug: Tusamitamab ravtansine+Sintilimab+Carboplatin or Cisplatin+Pemetrexed; Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous. Other Name: Tusamitamab ravtansine. Other Name: Tyvyt®
Placebo Comparator: Sintilimab + carboplatin/ cisplatin + pemetrexed; 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.	Drug: Sintilimab+Carboplatin or Cisplatin+Pemetrexed; Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) per RECIST 1.1 by investigators.	ORR is defined as proportion of participants who have a confirmed complete	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)		3 years
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).	3 years
Pharmacokinetic concentrations of tusamitamab ravtansine (IBI126)		3 years
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.	3 years
Progression-free Survival (PFS)		3 years
Time to Response (TTR)		3 years

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 30, 2023
• Primary Completion (Anticipated): April 30, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: April 17, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: CEACAM5
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Carboplatin; Cisplatin; Maytansine; Pemetrexed
• Other Study ID Numbers: CIBI126A201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No