Phase IIa Study of avelumab and cetuximab plus gemcitabine and cisplatin in participants with squamous NSCLC

Phase 1

• Conditions: on Small Cell Lung Cancer; MedDRA version: 20.0Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001529-24-ES
• Lead Sponsor: Merck KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-07
• Study Completion: 2021-05-27
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

Participants are eligible to be included in the study only if all the following criteria apply:
Age
1. Are 18 to 69 years inclusive, at the time of signing the informed consent

Type of Participant and Disease Characteristics
2. Histologically-confirmed Stage IV metastatic or recurrent (Stage IV) NSCLC of squamous histology as per the 7th International Association for the Study of Lung Cancer and the American Joint Committee on Cancer classifications.
3. Availability of formalin-fixed paraffin-embedded (FFPE) block containing tumor tissue or a minimum of 15 (preferably 25) unstained tumor slides (cut within 1 week) suitable for PD-L1 expression and EGFR expression/amplification assessments, from a recently obtained (within 6 months) biopsy or a fresh baseline tumor biopsy collected from a non-irradiated area.
4. At least 1 measurable lesion per RECIST v1.1 criteria. A lesion that has been irradiated can be used as a measurable lesion providing that disease has progressed at that site
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at study entry.
6. Adequate hematological function defined by white blood cell (WBC) count = 2.5 × 109/L with absolute neutrophil count (ANC) = 1.5 × 109/L, lymphocyte count = 0.5 × 109/L, platelet count = 100 × 109/L, and hemoglobin = 9 g/dL (may have been transfused).
7. Adequate hepatic function defined by a total bilirubin level = 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels = 2.5 × ULN except for participants with documented metastatic disease to the liver for whom AST and ALT levels = 5 × ULN are acceptable. Patients with documented Gilbert disease are allowed if total bilirubin is less than 3 × ULN.
8. Adequate renal function defined by an estimated creatinine clearance > 60 mL/minute according to the Cockcroft-Gault formula. or by 24-hour urine collection for creatinine clearance or according to local institutional standard method.
9. Estimated life expectancy of at least 3 months.

Sex
10. Are male or female.
A male participant must agree to use and to have their female partners use a highly effective contraception (i.e, methods with a failure rate of less than 1% per year) as detailed in Appendix 3 of this protocol 30 days before the first dose of study intervention (as appropriate), during the study intervention period and for at least 60 days after the last dose of study intervention and refrain from donating sperm during this period.
A female is eligible if she is not pregnant (i.e, after a confirmed menstrual period and a negative serum pregnancy test), not breastfeeding, and at least one of the following conditions applies:
a. Is not a woman of childbearing potential (WOCBP), as defined in Appendix 3
OR
b. Is a WOCBP who agrees to use a highly effective contraceptive method (i.e, has a failure rate of less than 1% per year), as listed in Appendix 3, 30 days before the start of the first dose of study intervention (as appropriate), during the study intervention period and for at least 60 days after the last dose of study intervention
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

1. Participants whose tumor disease harbors an activating EGFR mutation or ALK rearrangement. Participants with tumors of unknown EGFR or ALK status will require testing only in never smokers.
2. All participants with brain metastases, except those meeting the following criteria:
a. Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to treatment start.
b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable).
c. Participants must be either off steroids or on a stable or decreasing dose of < 10mg daily prednisone (or equivalent).
3. Previous malignant disease (other than NSCLC) within the last 5 years (except adequately
treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum,
breast, or prostate) unless a complete remission without further recurrence was achieved at
least 2 years prior to study entry and the participant was deemed to have been cured with no
additional therapy required or anticipated to be required.
4. Active infection requiring systemic therapy.
5. Known history of human immunodeficiency virus or known acquired immunodeficiency syndrome.
6. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV ribonucleic acid (RNA) if anti-HCV antibody screening test positive).
7. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent:
a. Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
b. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.
8. Interstitial parenchymal lung disease.
9. Pregnancy or lactation.
10. Known alcohol or drug abuse as determined by the Investigator.
11. History of uncontrolled intercurrent illness including but not limited to:
a. Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmHg or lower)
b. Uncontrolled active infection.
c. Uncontrolled diabetes (for example, hemoglobin A1c = 8%).
12. Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
13. Known history of inflammatory colitis, inflammatory bowel disease, pneumonitis, pulmonary
fibrosis.
14. Any psychiatric condition that would prohibit the understanding or rendering of informed consent or that would limit compliance with study requirements.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate efficacy by means of confirmed best overall response (BOR) rate of the combination of cetuximab and avelumab plus doublet chemotherapy, defined as the proportion of participants having achieved confirmed complete response (CR) or partial response (PR) as BOR;Secondary Objective: To evaluate the safety and tolerability of the combination of cetuximab and avelumab plus doublet chemotherapy<br>To evaluate the progression-free survival (PFS) time<br>To assess the duration of response;Primary end point(s): Confirmed BOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) assessed by Investigator;Timepoint(s) of evaluation of this end point: From the first dose of study intervention until planned final assessment at 17 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Occurrence of treatment-emergent adverse events (TEAEs) and treatment-related adverse events (AEs), treatment-related Grade = 3 AEs, and immune-related AEs, according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)<br>PFS time according to RECIST v1.1 by Investigator assessment<br>Duration of response (DOR) assessed from confirmed CR or PR until progression of disease (PD), death, or last tumor assessment;Timepoint(s) of evaluation of this end point: From the first dose of study intervention until planned final assessment at 17 months