A Single-Center, Single-Arm, Phase II Study of Benmelstobart Combined With Anlotinib and Chemotherapy as First-Line Treatment for Large-Cell Neuroendocrine Carcinoma of the Lung and Extrapulmonary Neuroendocrine Carcinoma

Plain English Summary

A Phase II Study of Benmelstobart + Anlotinib + Chemotherapy as First-Line Treatment for LCNEC and EP-NEC is a Phase 2 clinical trial sponsored by Tianjin Medical University Cancer Institute and Hospital studying Large-Cell Neuroendocrine Carcinoma of the Lung, Extrapulmonary Neuroendocrine Carcinoma. This study tests a combination of Benmelstobart, Anlotinib, and chemotherapy for specific types of advanced lung and other cancers. It is for patients with large-cell neuroendocrine carcinoma of the lung (LCNEC) or extrapulmonary neuroendocrine carcinoma (EP-NEC) that has spread and has not been treated with systemic therapy. Participation involves receiving the study drugs and regular check-ups. Alternatives may include standard chemotherapy or other treatments. This trial is for patients who have not received prior systemic treatment for their advanced cancer. The trial aims to enroll 48 participants.

Official Summary

To explore the Objective Response Rate (ORR) of Benmelstobart combined with Anlotinib and chemotherapy as first-line treatment for large-cell neuroendocrine carcinoma of the lung (LCNEC) and extrapulmonary neuroendocrine carcinoma (EP-NEC)

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with confirmed metastatic large-cell neuroendocrine carcinoma of the lung or extrapulmonary neuroendocrine carcinoma can join. You must be between 18 and 75 years old and have a good general health status (ECOG 0-1). Patients with brain metastases or certain other serious conditions, or those who have previously received specific anti-cancer drugs, may not be eligible. This trial is studying Large-Cell Neuroendocrine Carcinoma of the Lung, Extrapulmonary Neuroendocrine Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see how many patients' tumors shrink or disappear with this new drug combination, measured by imaging scans. The specific primary outcome measures are: Objective Response Rate (ORR) (per RECIST Version 1.1) (up to 12 months.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to find a new first-line treatment for rare and aggressive neuroendocrine cancers, addressing a significant unmet need in patient care. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Large-Cell Neuroendocrine Carcinoma of the Lung, Extrapulmonary Neuroendocrine Carcinoma, where improved treatment options are needed.

Investor Insight

This trial targets a niche but aggressive cancer type, with potential for a novel combination therapy to improve outcomes, signaling a potential new treatment option in a competitive oncology market. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific chemotherapy drugs used, the duration of treatment, and potential side effects. You will need to attend regular clinic visits for drug administration, blood tests, and imaging scans to monitor your response and health. Be prepared for potential side effects and discuss any concerns with your healthcare team promptly. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 48 participants

Interventions

• DRUG: Benmelstobart+ Anlotinib+ Platinum + Etoposide — Treatment phase (intensive combination treatment) : 4 cycles, with each treatment cycle lasting 21 days: 1) Benmelstobart: 1200mg per dose, administered intravenously (IV) once every 21 days; 2) Anlotinib: 12mg per dose, taken orally (po) for 2 consecutive weeks followed by 1 week of rest; 3) Carboplatin: administered on Day 1, with an AUC of 5mg/mL/min via IV infusion (maximum dose: 750mg); \& Cisplatin: administered on Day 1, 75-80mg/m² via IV infusion; 4) Etoposide: administered continuously

Primary Outcomes

• Objective Response Rate (ORR) (per RECIST Version 1.1) (up to 12 months.)

Full Eligibility Criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed metastatic LCNEC or EP-NEC (per AJCC 9th Edition);
2. No prior systemic treatment for locally advanced or metastatic LCNEC or EP-NEC; For patients who have received adjuvant chemo/radiotherapy, neoadjuvant chemo/radiotherapy for non-metastatic disease with curative intent, or definitive chemoradiotherapy for locally advanced disease, the interval from the end of chemotherapy, radiotherapy, or chemoradiotherapy to the diagnosis of metastatic NEC must be at least 6 months (calculated from the end date of the last chemotherapy cycle or the end date of the last radiotherapy);
3. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; Lesions that have received prior radiotherapy can be considered measurable only if there is clear progression after radiotherapy and they are not the only lesion;
4. Aged 18-75 years;
5. ECOG Performance Status 0-1;
6. Life expectancy ≥3 months;
7. Sufficient hematological and organ function, meeting the following criteria:

   1. Hematology (no blood transfusion or blood products within 14 days, no correction with G-CSF or other hematopoietic stimulants): Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L; Platelet Count (PLT) ≥100×10⁹/L; White Blood Cell (WBC) Count ≥3×10⁹/L;
   2. Biochemical tests:

      Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5×Upper Limit of Normal (ULN), or ≤5×ULN in patients with liver metastasis; Total Bilirubin (TBIL) ≤1.5×ULN, or ≤3×ULN in patients with Gilbert's syndrome; Creatinine (Cr) ≤1.5×ULN or Creatinine Clearance (CCr) ≥50mL/min;
   3. Coagulation function:

      Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR), or Prothrombin Time (PT) ≤1.5×ULN;
   4. Doppler ultrasound assessment:

   Left Ventricular Ejection Fraction (LVEF) ≥50%;
8. Women and men of childbearing potential must agree to use contraceptive measures (e.g., intrauterine device \[IUD\], contraceptive pills, or condoms) during the study treatment period and within 6 months after the last dose of study medication; Women must have a negative serum pregnancy test within 7 days before study randomization and must not be breastfeeding;
9. Subjects voluntarily participate in this study, sign the informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. Patients with brain metastasis and/or carcinomatous meningitis (excluding asymptomatic patients or patients with stable condition who have no imaging evidence of new/enlarged central nervous system metastasis for at least 2 weeks after brain metastasis treatment and have discontinued steroids or anticonvulsants for at least 14 days before the study; If active or new untreated asymptomatic central nervous system metastasis is detected during the screening phase, subjects must receive radiotherapy, or have no imaging evidence of new/enlarged brain metastasis for at least 2 weeks without treatment);
2. Prior use of anti-angiogenic drugs such as Anlotinib, Apatinib, Bevacizumab, or immunotherapeutic drugs targeting PD-1, PD-L1, etc.;
3. History of other malignant tumors within 5 years (except cured carcinoma in situ of the cervix or basal cell carcinoma of the skin);
4. Factors affecting oral drug administration (dysphagia, post-gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.);
5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
6. Spinal cord compression not cured or relieved by surgery and/or radiotherapy, or no clinical evidence of stable condition for ≥1 week after treatment of previously diagnosed spinal cord compression before randomization;
7. Imaging (Computed Tomography \[CT\]/Magnetic Resonance Imaging \[MRI\]) showing tumor invasion of large blood vessels or unclear boundary with large blood vessels;
8. Patients with imaging evidence of tumor invasion around major blood vessels, or judged by the investigator to have a high risk of tumor invading major blood vessels leading to fatal massive hemorrhage during the subsequent study period;
9. History of severe bleeding tendency or coagulation dysfunction, including but not limited to: clinically significant hemoptysis (hemoptysis \>1 tablespoon per day) within 3 months before enrollment; or bleeding symptoms or bleeding tendency of significant clinical significance within 4 weeks before randomization, such as gastrointestinal bleeding, hemorrhagic gastric ulcer (including gastrointestinal perforation and/or fistula, except for patients with gastrointestinal perforation or fistula who have undergone surgical resection and are eligible for enrollment), unhealed wounds, ulcers, or fractures;
10. Unresolved treatment-related toxicity (\>Grade 1) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (except alopecia);
11. Major surgical treatment, incisi

Trial Locations

• Tianjin Medical University Cancer Institute & Hospital, Tianjin, Tianjin Municipality, China

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Neuroendocrine Tumors
• Small Cell Lung Cancer
• Gastrointestinal Neuroendocrine Tumors
• Pancreatic Neuroendocrine Tumors
• Carcinoid Tumors
• Metastatic Cancer
• Oncology
• Chemotherapy
• Targeted Therapy

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