Condition

• Extensive Stage Lung Small Cell Cancer

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Selection Criteria:

- Patients must have pathologically confirmed Extensive Stage Small Cell Lung Cancer
(ES-SCLC).

- No prior systemic therapy for the disease under study (ES-SCLC).

- Patients must have measurable disease according to Response Evaluation Criteria for
Solid Tumors (RECIST) v1.1.

- Patient must be ≥ 18 years of age.

- Patient must have an ECOG performance status of 0-1.

- Patient must have the ability to understand and willingness to sign a written
informed consent document.

- Willing to provide archived tumor tissue (if sufficient tumor tissue available) and
blood samples for research.

- Patient must have adequate organ function and marrow function as defined below,
obtained ≤ 14 days prior to registration/randomization. No blood transfusions or
growth factor therapy allowed within 7 days of screening labs.

- Absolute Neutrophil Count (ANC) ≥ 1500/microliter (mcL)

- Platelets ˃100,000/mcL

- Hemoglobin >9.0 gram/deciliter (g/dL)

- Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5x Upper
Limit Normal (ULN), and partial prothrombin time (PTT) or activated partial
thromboplastin time (aPTT) ≤ 1.5x ULN

- Serum Creatinine ≤ 2x ULN

- Creatinine clearance (CrCl) ≥ 50 milliliter/minute (mL/min)

- Urine Protein <2+

- Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5x ULN
or ≤ 5x ULN for patients with liver metastasis

- Total Bilirubin ≤ 1.5x ULN or ≤ 3x ULN for patients with liver metastasis or
suspected/documented Gilbert's disease

- Patient must not be pregnant or breast-feeding due to the potential harm to an
unborn fetus and possible risk for adverse events in nursing infants with the
treatment regimens being used.

- Patient must not expect to conceive or father children by using an accepted and
effective method(s) of contraception or by abstaining from sexual intercourse for
the duration of their participation in the study, and for 120 days after the last
dose of study drug(s).

- Patients must not have symptomatic central nervous system (CNS) metastases, CNS
metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to randomization, potential
need for CNS radiation within the first cycle, or leptomeningeal disease.

- Patients must not have imaging during the screening period that shows:

1. Radiologically documented evidence of major blood vessel invasion (central
pulmonary artery, central pulmonary veins, aorta, brachiocephalic artery,
common carotid artery, subclavian artery, superior vena cava) or tumor invading
organs (heart, trachea, esophagus, central bronchi [not including segmental
bronchi]) or if there is a risk of esophagotracheal or esophagopleural fistula
.

2. Radiographic evidence of major blood vessel encasement with narrowing of the
vessel or intratumor lung cavitation or necrosis that the investigator
determines will pose a significantly increased risk of bleeding.

- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial.

- Patients must not have major surgical procedures or serious trauma within 28 days
prior to randomization or plans for major surgical procedures within 28 days after
the first dose.

- Patients must not have history of bleeding tendencies or coagulopathy and/or
clinically significant bleeding symptoms or risk within 4 weeks prior to
randomization, including but not limited to:

1. Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood
clots). Transient hemoptysis associated with diagnostic bronchoscopy is
allowed.

2. Nasal bleeding/epistaxis (bloody nasal discharge is allowed).

3. Current use of prophylactic or full-dose anticoagulants or anti-platelet agents
for therapeutic purposes that is not stable prior to randomization is not
allowed.

- Patients must not have history of major diseases before randomization, specifically:

1. Unstable angina, myocardial infarction, congestive heart failure (New York
Heart Association (NYHA) classification ≥ Grade 2) or unstable vascular disease
(e.g., aortic aneurysm at risk of rupture, Moyamoya disease) that required
hospitalization within 12 months prior to randomization, or other cardiac
impairment that may affect the safety evaluation of the study drug (e.g.,
poorly controlled arrhythmias, myocardial ischemia).

2. History of any grade arterial thromboembolic event, Grade 3 and above venous
thromboembolic event, as specified in National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack,
cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy
within 12 months prior to randomization.

3. History of esophageal gastric varices, severe ulcers, wounds that do not heal,
abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal
bleeding within 6 months prior to randomization.

4. History of perforation of the gastrointestinal tract and/or fistula, history of
gastrointestinal obstruction (including incomplete intestinal obstruction
requiring parenteral nutrition), extensive bowel resection (partial colectomy
or extensive small bowel resection) within 6 months prior to randomization.

- Patients must not have poorly controlled hypertension with repeated systolic blood
pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral
antihypertensive therapy.

- Patients must not have prolongation of QTc interval >480 msec

- Patients must not have active autoimmune or lung disease requiring systemic therapy
(e.g., with disease modifying drugs, prednisone >10 mg daily or equivalent,
immunosuppressant therapy) within 2 years prior to randomization.

- Patients must not have severe infection within 4 weeks prior to randomization,
including but not limited to comorbidities requiring hospitalization, sepsis, or
severe pneumonia; active infection requiring systemic anti-infective therapy within
2 weeks prior to randomization (excluding antiviral therapy for hepatitis B or C).

- Patients must not have uncontrolled pleural effusions, pericardial effusions, or
ascites that is clinically symptomatic.

- Patients must not have history of non-infectious pneumonia requiring systemic
corticosteroids, or current interstitial lung disease.

- Patients must not have active or prior history of inflammatory bowel disease (e.g.,
Crohn's disease, ulcerative colitis, or chronic diarrhea.

- Patients must not have pre-existing peripheral neuropathy ≥ Grade 2 by CTCAE V5.0.

- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of registration/randomization
are eligible for this trial.

- Patient must not have received any live vaccine within 28 days prior to
registration/randomization.

- Patients with a known allergy to any of the study medications, their analogues, or
excipients in the various formulations of any agent are not eligible.

- Patients with any serious medical or psychiatric illness that could, in the
investigator's opinion, potentially interfere with the completion of the treatment
according to the protocol are not eligible.

- Patients may not participate in any other therapeutic clinical trials, including
those with other investigational agents not included in this trial during treatment
on this study without prior approval from PrECOG.

Recruiting Locations

Study Contact

Detailed Description

Randomized, Phase II, open-label trial designed to determine the optimal dose of ivonescimab with carboplatin and etoposide for a more diverse Western participant population with ES- SCLC based on overall response rate and safety profile of two dose levels of ivonescimab (10 mg/kg versus 20 mg/kg) previously evaluated in the Chinese population. The simultaneous blockade of vascular endothelial growth factor (VEGF) and Programmed Death-Ligand 1 (PDL-1) by ivonescimab may achieve a higher target binding of VEGF and PD-1 within the tumor microenvironment and produce increased anti-tumor effect with an improved safety profile than administration of anti-PD-(L)1 and anti-VEGF therapies separately. Participants will be randomized 1:1 to receive ivonescimab 10 mg/kg or 20 mg/kg. Induction treatment will be administered on a 21-day cycle for four cycles with standard of care carboplatin and etoposide. Following the induction phase, participants will continue maintenance therapy with ivonescimab on a 21-day cycle at the dose received during induction (10 mg/kg or 20 mg/kg). Treatment will be discontinued in all participants who have evidence of progressive disease by Response Criteria Evaluation in Solid Tumors version 1.1 (RECIST v1.1). Research tumor tissue will be requested at baseline for future research. Research blood samples will also be obtained for future research which may include measuring the level of ivonescimab in the blood and immune responses or antibodies to ivonescimab.