Bintrafusp Alfa With Chemotherapy for Tyrosine Kinase Inhibitor-Resistant EGFR-Mutant Non-small Cell Lung Cancer

NCT04971187 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2020-1266NCI-2021-07070
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of bintrafusp alfa with pemetrexed and platinum-based chemotherapy (carboplatin or cisplatin) in treating patients with EGFR mutant non-small cell lung cancer that have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic) and cannot be removed by surgery, and remains despite treatment with tyrosine kinase inhibitors (Resistant). Immunotherapy with bintrafusp alfa, a bifunctional fusion protein composed of the monoclonal antibody anti-PD-L1 and TGF-beta, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as carboplatin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bintrafusp alfa with pemetrexed and platinum-based chemotherapy may help to control the disease.

Conditions

Locally Advanced Lung Non-Squamous Non-Small Cell Carcinoma; Metastatic Lung Non-Squamous Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Unresectable Lung Non-Squamous Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Best Objective Response Rate (ORR) Within 6 Months

  Objective response was assessed by RECIST 1.1. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

  Within 6 months since initiation of treatment

• Progression Free Survival (PFS) at 18 Weeks

  PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per Response evaluation criteria in solid tumors (RECIST) version 1.1 at 18 weeks.

  18 weeks

Secondary Outcomes (5)

• Safety and Tolerability

  Up to 30 days post-treatment

• Progression Free Survival (PFS)

  Up to 1 year

• Disease Control Rate (DCR)

  Up to 1 year

• Duration of Response (DoR)

  Up to 1 year

• Overall Survival (OS)

  Up to 1 year

Study Arms (1)

Treatment (bintrafusp alfa, pemetrexed, carboplatin/cisplatin)

EXPERIMENTAL

Patients receive bintrafusp alfa IV over 1 hour on day 1 and pemetrexed IV over 10 minutes on day 1. Patients also receive carboplatin IV over 15 minutes or cisplatin IV over 6-8 hours at the physician's discretion on day 1 of cycles 1-4. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Bintrafusp Alfa; Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin

Interventions

Bintrafusp Alfa DRUG

Given IV

Also known as: 1918149-01-5, Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C

Treatment (bintrafusp alfa, pemetrexed, carboplatin/cisplatin)

Pemetrexed DRUG

Given IV

Also known as: 137281-23-3, L-Glutamic Acid, N-(4-(2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo(2,3-d)pyrimidin-5-yl)ethyl)benzoyl), MTA, Multitargeted Antifolate, Pemfexy

Treatment (bintrafusp alfa, pemetrexed, carboplatin/cisplatin)

Carboplatin DRUG

Given IV

Also known as: (SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O'']platinum, 1-cyclobutanedicarboxylic acid platinum complex, 41575-94-4, Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, cis-diammine(1,1-cyclobutanedicarboxylato) platinum(II), Cis-Diammine(cyclobutane-1,1-dicarboxylato)platinum, cis-diammine(cyclobutanedicarboxylato)platinum II, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, platinum, diammine(1,1-cyclobutanedicarboxylato(2-))-, Platinwas, Ribocarbo

Treatment (bintrafusp alfa, pemetrexed, carboplatin/cisplatin)

Cisplatin DRUG

Given IV

Also known as: (SP-4-2)-Diamminedichloroplatinum, 15663-27-1, Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Diaminedichloro-, cis- (8CI), Platiran, Platistin, Platosin

Treatment (bintrafusp alfa, pemetrexed, carboplatin/cisplatin)

Eligibility Criteria

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

You may qualify if:

• Age equal or greater than 18 years old and willing to give their signed consent
• Histologically or cytologically confirmed non-squamous, non-small cell lung cancer
• Locally advanced or metastatic disease, not amenable to curative surgery or radiotherapy
• Patients must have one of the following:
• NSCLC which harbors EGFR Exon 19 deletion.
• NSCLC which harbors EGFR L858R mutation.
• NSCLC which harbors EGFR G719X, S768X, L861X mutation, and other activating uncommon mutations in exon 18-21
• NSCLC which harbors EGFR exon20 insertion
• NSCLC which harbors EGFR T790M mutation EGFR deletion/mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• At least one target lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline at equal or greater than 10 mm in the longest dimension by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patients must have received at least one line of EGFR tyrosine kinase inhibitor (TKI) treatment, if an Food and Drug Administration (FDA)-approved treatment exist for the EGFR mutation. Patients whose tumor harboring EGFR T790M mutation must have received prior osimertinib (or another EGFR TKI with demonstrated activity against T790M mutation). Patients who received more than one EGFR TKIs are eligible. Up to two lines of TKIs are allowed
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3 (obtained less than 4 weeks from study entry)
• Platelet count \>= 100,000/mm\^3 (obtained less than 4 weeks from study entry)
• Hemoglobin (HgB) \>= 9 g/dL (obtained less than 4 weeks from study entry)

You may not qualify if:

• Previous treatments with cytotoxic chemotherapy or checkpoint immunotherapy or combination of chemo-immunotherapy for metastatic disease. If the patient had prior chemotherapy as neoadjuvant or adjuvant therapy, the completion of treatment must be greater than 6 months until the beginning of the treatment on trial
• Previous treatment with any anti-TGF-beta medications
• Spinal cord compression or brain metastases unless asymptomatic or stable for at least 2 weeks prior to start of study treatment
• Persisting grade \> 1 Common Terminology Criteria for Adverse Events (CTCAE) 5.0 toxicity (except alopecia and vitiligo) related to prior therapy; however, sensory neuropathy grade =\< 2 is acceptable
• Current use of immunosuppressive medication, EXCEPT for the following:
• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
• Systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography \[CT\] scan premedication).
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible
• Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids
• No previous malignant disease within the last 3 years except for a. superficial/non-invasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected gastrointestinal (GI) cancers limited to the mucosal layer without recurrence in \> 1 year
• No prior organ transplantation including allogenic stem-cell transplantation, except transplants that do not require immunosuppression
• Active infection requiring systemic therapy
• Live vaccination that has received or will receive within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. COVID-19 vaccines are permitted
• Known severe hypersensitivity (grade \>= 3 National Cancer Institute \[NCI\] CTCAE 5.0) to investigational product or any component in its formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

bintrafusp alfa protein, human; Pemetrexed; Glutamic Acid; Carboplatin; Platinum; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; cytokine inducible SH2-containing protein

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Excitatory Amino Acids; Coordination Complexes; Organic Chemicals; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

The study was terminated early due to the drug company no longer producing the drug.

Results Point of Contact

• Title: Dr. Xiuning Le
• Organization: M D Anderson Cancer Center

xle1@mdanderson.org

(713) 792-6980

Study Officials

• Xiuning Le

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: July 21, 2021
• Study Start: June 30, 2021
• Primary Completion: February 21, 2022
• Study Completion: February 21, 2022
• Last Updated: August 1, 2023
• Results First Posted: August 1, 2023

Record last verified: 2023-07

Locations

US (1)