Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer

NCT04285671 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 19-002190NCI-2020-00677
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies the side effects and best dose of trastuzumab and necitumumab together with osimertinib, and to see how well they work for the treatment of stage IV non-small cell lung cancer that is EGFR-mutated, resistant to osimertinib, and has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as trastuzumab and necitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving trastuzumab and necitumumab together with osimertinib may work better than osimertinib alone in treating patients with stage IV EGFR-mutated non-small cell lung cancer.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Refractory Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer American Joint Committee on Cancer (AJCC) v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (3)

• Identification of the recommended phase II dose (R2PD) regimen for combination osimertinib, necitumumab, trastuzumab (ONT) therapy (Phase Ib)

  Up to 1 year

• Incidence of adverse events (Phase Ib)

  Will be defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0).

  Up to 1 year

• Objective response rate (ORR) (Phase II)

  Will be based on the Full Analysis Set (FAS) of the phase II portion of the trial and the phase Ib patients treated at the recommended phase II dose (RP2D). ORR is defined as defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be determined by the investigator. A Cox proportional hazards model will be used to estimate the hazard ratio and its 95% confidence interval (CI).

  Up to 1 year

Secondary Outcomes (5)

• Progression free survival (PFS) (Phase II)

  Up to 1 year

• Duration of response (DoR) (Phase II)

  Up to 1 year

• Overall survival (OS) (Phase II)

  Up to 1 year

• Time to response (TTR)

  Up to 1 year

• Patient reported outcomes (PROs)

  Up to 1 year

Other Outcomes (3)

• Quality of life data questionnaire

  Up to 1 year

• Potential biomarkers associated with response from liquid biopsies

  Up to 1 year

• Mutant allele fraction in circulating tumor deoxyribonucleic acid (DNA) (ctDNA)

  Up to 1 year

Study Arms (1)

Treatment (necitumumab, trastuzumab, osimertinib)

EXPERIMENTAL

Patients receive necitumumab IV over 60 minutes and trastuzumab IV over 30-90 minutes on days 1 and 15. Patients also receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Necitumumab; Drug: Osimertinib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Trastuzumab

Interventions

Necitumumab BIOLOGICAL

Given IV

Also known as: Anti-Epidermal Growth Factor Receptor Monoclonal Antibody IMC-11F8, IMC-11F8, Portrazza

Treatment (necitumumab, trastuzumab, osimertinib)

Osimertinib DRUG

Given PO

Also known as: AZD-9291, AZD9291, Mereletinib, Tagrisso

Treatment (necitumumab, trastuzumab, osimertinib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (necitumumab, trastuzumab, osimertinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (necitumumab, trastuzumab, osimertinib)

Trastuzumab BIOLOGICAL

Given IV

Also known as: ABP 980, ALT02, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Herzuma, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, Ogivri, Ontruzant, PF-05280014, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar SB3, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-QYYP, Trazimera

Treatment (necitumumab, trastuzumab, osimertinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide informed consent
• Cytologically or histologically confirmed non-small cell lung cancer (NSCLC), that is stage IV (metastatic), with an activating and sensitizing EGFR mutation (e.g., exon 20 insertion mutations are excluded). Enrollment of patients with mutations other than exon 19 deletion and the L858R point mutation require literature supporting sensitivity to EGFR tyrosine kinase inhibitors
• Progressed on osimertinib. Osimertinib must have been included as the last systemic therapy prior to trial enrollment. This excludes patients who received osimertinib in combination with other EGFR-tyrosine kinase inhibitor (TKI) or anti-human epidermal growth factor receptor (anti-HER) therapy
• Measurable disease, as per RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Able to swallow the study drugs, has no known intolerance of study drugs or excipients, and able to comply with study requirements
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 50 mL/min for participants with creatinine levels \> 1.5 X institutional ULN (Glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\])
• Creatinine clearance may be calculated following institutional practices
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN.
• If a patient experiences elevated alanine aminotransferase (ALT) \> 5 X ULN and elevated total bilirubin \> 2 X ULN, clinical and laboratory monitoring should be initiated by the investigator. For patients entering the study with ALT \> 3 X ULN, monitoring should be triggered at ALT \> 2 X baseline
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and ALT (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for participants with liver metastases.
• If a patient experiences elevated ALT \> 5 X ULN and elevated total bilirubin \> 2 X ULN, clinical and laboratory monitoring should be initiated by the investigator. For patients entering the study with ALT \> 3 X ULN, monitoring should be triggered at ALT \> 2 X baseline

You may not qualify if:

• Concurrent enrollment in another clinical study, unless enrolled only in the follow-up period or an observational study
• Any chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment in the prior 3 weeks, other than osimertinib. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. Stereotactic, palliative radiation for symptomatic bone metastases is acceptable without a washout. Stereotactic brain radiation for asymptomatic brain metastases is acceptable with a 7 day washout
• Use of any investigational anticancer therapy received within 28 days prior to the first dose of study drugs
• Prior treatment with the combination of two or more of the following therapies which target EGFR/HER: osimertinib (Tagrisso), erlotinib (Tarceva), gefitinib (Iressa), afatinib (Gilotrif), lapatinib (Tykerb), neratinib (Nerlynx), vandetanib (Caprelsa), cetuximab (Erbitux), trastuzumab (Herceptin), pertuzumab (Perjeta), ado-trastuzumab emtansine (Kadcyla), panitumumab (Vectibix), necitumumab (Portrazza), dacomitinib (Vizimpro), poziotinib, or other combination deemed as "combined HER-inhibition therapy" by the investigator
• Known small cell lung cancer or small cell transformation
• The patient has a known allergy / history of hypersensitivity reaction to any of the treatment components or any other contraindication to one of the administered treatments
• History or evidence of current clinically relevant coronary artery disease \>= grade III by the Canadian Cardiovascular Society Angina Grading Scale or uncontrolled congestive heart failure of current \>= class III as defined by the New York Heart Association, or unstable cardiac arrhythmia requiring medication (atrial fibrillation is permitted if clinically stable)
• The patient has experienced myocardial infarction within 6 months prior to study enrollment
• The patient has any ongoing or active infection, including active tuberculosis or known infection with the human immunodeficiency virus, or active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade \> 2 by NCI CTCAE (v5.0) within 14 days prior to enrollment
• The patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment
• Progressive or symptomatic brain metastases. Brain metastases that have been radiated, are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded
• Serious accompanying disorder or impaired organ function, including major surgery within 3 weeks before randomization
• Requirement for IV alimentation (at the time of enrollment)
• History of another cancer within 2 years of study initiation, with the exception of fully treated cancers unlikely to affect the assessment of the study treatment safety or efficacy including early stage breast, prostate, non-melanomatous skin, thyroid, cervical, or endometrial cancer
• Gastrointestinal disorder affecting absorption

Sponsors & Collaborators

• Eli Lilly and Company: collaborator
• Genentech, Inc.: collaborator
• Jonsson Comprehensive Cancer Center: lead

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

necitumumab; osimertinib; Trastuzumab; PF-05280014; Ogivri; Ontruzant; trastuzumab biosimilar HLX02

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jonathan W Goldman

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: February 26, 2020
• Study Start: January 29, 2021
• Primary Completion (Estimated): December 2, 2026
• Study Completion (Estimated): December 2, 2027
• Last Updated: March 10, 2026

Record last verified: 2025-06

Locations

US (1)