Bintrafusp Alfa and Pimasertib for the Treatment of Patients With Brain Metastases

NCT04789668 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2019-1091NCI-2021-00219
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the best dose and effect of pimasertib in combination with bintrafusp alfa in treating patients with cancer that has spread to the brain (brain metastases). 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. Pimasertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pimasertib and bintrafusp alfa may help to prevent or delay the cancer from progressing (getting worse) and/or coming back.

Conditions

Hormone Receptor Positive Breast Adenocarcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Neoplasm in the Brain; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Triple-Negative Breast Carcinoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Hematopoietic and Lymphoid Cell Neoplasm

Outcome Measures

Primary Outcomes (2)

• Phase I - Determine Phase II Dose

  Establish safety profile and recommended phase II dose for combining pimasertib with bintrafusp alfa (M7824) in patients with brain metastases.

  Up to 2 years

• Time to Intracranial Progression (Phase II)

  Time to intracranial progression (defined as progression of existing lesions and development of new lesions by modified RECIST 1.1) and Overall survival

  Baseline up to 2 years

Secondary Outcomes (4)

• Intracranial Progression Free Survival

  Baseline up to 18 months

• Overall Survival

  From treatment start date to death, assessed up to 2 years

• Time to Second Intracranial Progression

  From the time of study enrollment to intracranial progression (event) or the last follow-up date if the patient has not developed the intracranial progression yet

• Dose, Duration and Frequency of Steroid Use for Symptomatic Management

  baseline to 1 year

Study Arms (1)

Treatment (bintrafusp alfa, pimasertib)

EXPERIMENTAL

Patients receive bintrafusp alfa IV over 1 hour every 2 weeks and pimasertib PO BID on days 1-28. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Drug: Bintrafusp Alfa; Drug: Pimasertib; Other: Quality-of-Life Assessment

Interventions

Bintrafusp Alfa DRUG

Given IV

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

Treatment (bintrafusp alfa, pimasertib)

Pimasertib DRUG

Given PO

Also known as: AS703026, EMD 1036239, MSC1936369

Treatment (bintrafusp alfa, pimasertib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (bintrafusp alfa, pimasertib)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years old
• Life expectancy \> 12 weeks
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
• At least one measurable untreated brain lesion \>= 0.5 cm and \< 3.0 cm in the longest axis according to modified RECIST 1.1
• Prior stereotactic radiosurgery (SRS) with up to 3 lesions treated with at least a 14 day interval is allowed as long as the previous treatment volume does not overlap with the current targets
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy in the 10 days prior to beginning protocol therapy
• Prior treatment with immunotherapy and targeted therapy allowed as long as it did not include a combination of MEK inhibitor (i) + anti-PD(L)-1 antibody and is \> 14 days prior to start of protocol therapy. All tumor types will be eligible and included in the dose escalation phase. Dose expansions will include 10 patients each from lung, breast, and melanoma
• Patients with melanoma must have received prior PD-1 based therapy and have evidence of progression
• Patients with non-small cell lung cancer (NSCLC) must have received prior PD-1 based therapy and have evidence of progression
• Patients with triple-negative breast cancer (TNBC) and hormone receptor positive (HR+) are included (any number of prior lines of therapy-including immuno-oncology \[IO\] naive patients)
• For HR+ patients, patients are allowed to receive endocrine therapy with or without CDK4/6 inhibitors per treating physician discretion (Arimidex, letrozole, exemestane, or fulvestrant)
• Systematic radiation therapy is allowed (\> 14 day washout)
• Prior platinum-based chemotherapy for NSCLC patients is allowed
• Absolute neutrophil count (ANC) \>= 1500/uL

You may not qualify if:

• Patients with clinical or radiographic evidence of leptomeningeal disease
• Those who experienced grade 3 or 4 neurotoxicity from prior SRS
• Prior external beam radiation to the brain or whole brain radiation
• Contraindications to MRI (implanted metal device or foreign bodies) or MRI contrast (insufficient renal function or allergy)
• Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled
• Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the principle investigator (PI). Examples of the latter include basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, and isolated elevation of prostate-specific antigen. Subjects with a completely treated prior malignancy and no evidence of disease for \>= 2 years are eligible
• Has a known history of or is positive for hepatitis B (hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus infection (note treated and cured history of hepatitis C is allowed) (hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
• Note: Without known history, testing needs to be performed to determine eligibility. Hepatitis C antibody (Ab) testing is allowed for screening purposes in countries where HCV RNA is not part of standard of care
• Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
• The use of corticosteroids is not allowed for 10 days prior to initiation of therapy (based upon 5 times the expected half-life of dexamethasone) except patients who are taking steroids for physiological replacement. If alternative corticosteroid therapy has been used, consultation with the PI is required to determine the washout period prior to initiating study treatment
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study initiation. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
• Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug (unless the wound has healed) or anticipation of the need for major surgery during the study
• Non-healing wound, ulcer, or bone fracture
• Women who are breast-feeding or pregnant
• Subjects with a history of serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, bleeding diathesis or recent major bleeding events or other illness considered by the Investigator as high risk for investigational drug treatment

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Hematologic Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Neoplasm Metastasis; Melanoma; Triple Negative Breast Neoplasms; Lung Neoplasms

Interventions

bintrafusp alfa protein, human; N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Diseases

Results Point of Contact

• Title: Dr. Hussein Tawbi
• Organization: The University of Texas MD Anderson Cancer Center

htawbi@mdanderson.org

(713) 792-4185

Study Officials

• Hussein A Tawbi, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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 8, 2021
• First Posted: March 9, 2021
• Study Start: January 15, 2021
• Primary Completion: December 8, 2023
• Study Completion: December 8, 2023
• Last Updated: March 18, 2026
• Results First Posted: March 18, 2026

Record last verified: 2026-03

Locations

US (1)