Neratinib and Capmatinib Combination (Phase Ib/II) in Metastatic Breast Cancer and Inflammatory Breast Cancer Patients With Abnormal HER-family and c-Met Pathway Activity as Measured by the CELsignia Signaling Analysis Test

NCT05243641 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2020-0198NCI-2022-01130
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to learn if the combination therapy of capmatinib and neritinib can help to control metastatic or locally advanced breast cancer. Researchers also want to find the highest tolerable dose of the combination therapy of capmatinib and neritinib that can be used in this study drug combinations. The safety of this drug combination and the CELsignia MP test methodology will also be studied.

Conditions

Metastatic Breast Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (2)

• To Determine Maximum Tolerated Dose for Use in the Phase II Portion of the Trial

  This phase of the study uses the Bayesian Optimal Interval (BOIN) design with a 3+3 run-in to identify the maximum tolerable dose (MTD). Patients are treated in cohorts of 3 with a maximum of 27 participants. Starting with Neratinib PO dose level 1 (120 mg for Dose 1-7, then 160 mg) combined with Capmatinib PO level 1 (400 mg), with up to 12 patients per dose. The target toxicity rate for the MTD is 25%.

  Cycle1 and 2, total 56 days

• To Determine Overall Response Rate

  The overall response rate (ORR) for patients treated at the MTD in Phase II was assessed. ORR was defined as the proportion of patients who achieved a partial response or complete response as their best response. All tumor responses were evaluated according to RECIST 1.1 criteria and measured using the QIAC system.

  Up to 3 years

Secondary Outcomes (5)

• To Further Characterize the Safety and Tolerability of Neratinib + Capmatinib

  Up to 3 years

• To Determine Clinical Benefit Rate (CBR)

  Up to 27 months

• To Determine the Duration of Response (DOR)

  Up to 27 months

• To Determine Progression Free Survival (PFS)

  Up to 27 months

• To Determine 2 Year Overall Survival (OS)

  2 years after enrollment

Study Arms (2)

Part 1b (dose escalation)

EXPERIMENTAL

This portion of the study will enroll a maximum of 27 patients in the dose-finding trial including the possibility of adding up to 6 additional ER+ patients in a safety assessment of aromatic inhibitor treatment

Drug: Neratinib; Drug: Capmatinib

Part 2 (dose expansion)

EXPERIMENTAL

This portion of the study will enroll a maximum of 29 patients

Drug: Neratinib; Drug: Capmatinib

Interventions

Neratinib DRUG

Nertatinib will be supplied as 40 mg tablets, equivalent to 48.31 mg neratinib maleate.

Part 1b (dose escalation); Part 2 (dose expansion)

Capmatinib DRUG

Capmatinib will be supplied at 200 mg and 150 mg tablets

Part 1b (dose escalation); Part 2 (dose expansion)

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form (ICF) and comply with the requirements of the study protocol
• Age ≥ 18 years.
• ECOG performance status 0-1
• Confirmed diagnosis of metastatic breast cancer or inflammatory breast cancer according to international consensus criteria:
• Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass
• Duration: History of such findings no more than 6 months
• Extent: Erythema occupying at least 1/3 of whole breast
• Pathology: Pathologic confirmation of invasive carcinoma
• Patients who have metastatic disease which is not amenable to curative treatment with available local and systemic therapy. Patients must have received at least 1 line or up to 6 lines of therapy in the metastatic setting with at least 2 weeks washout period before the initiation of study treatment.
• i. Unless a contraindication to therapy exists, patients with ER+ breast cancer must have received prior endocrine therapy combined with a CDK4/6 inhibitor, patients with BRCA1 or BRCA2 mutations must have received prior PARP inhibitor, and patients with PD-L1+ triple negative breast cancer must have received prior immunotherapy.
• ii. Patients with HER2-positive disease must have received at least 2 regimens of anti-HER2 therapy in metastatic setting.
• For Phase Ib, any ER, PR, and HER2 status, For Phase 2, HER2-negative per ASCO/CAP guidelines and any ER and PR status.
• For Phase II only, Patients with measurable disease according to the Response Evaluation Criteria in Solid Tumor (RECIST, v1.1) (local or distant) and at least one metastatic lesion amenable for biopsy (core or punch)
• NOTE:
• Measurable disease: Measurable lesions are defined as those that can be accurately measured in at least one-dimension (longest diameter to be recorded) as ≥ 20mm by chest X-ray, ≥ 10mm by computed tomography (CT) scan, ≥ 10mm with calipers by clinical exam.

You may not qualify if:

• Concurrent anticancer therapy within 2 weeks of initiation of study treatment; except:
• i. Endocrine therapy (SERM, aromatase inhibitor, fulvestrant, medical ovarian suppression therapy) ii. Palliative radiotherapy for bone metastases \< 1 week prior to study treatment
• Unstable and symptomatic brain metastasis (Stable disease is defined as CNS radiographic study ≥ 4 weeks from completion of radiotherapy and ≥ 2 weeks from discontinuation of corticosteroids)
• Non-hematologic adverse events from prior anticancer therapy that have not resolved to Grade ≤ 1 (CTCAE v 5.0), except for alopecia, vitiligo, pain, constipation if these symptoms existed during screening baseline.
• i. Grade 3 or above neuropathy induced from prior treatment, that is not resolved to grade 2 or below despite best supportive care
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis
• Acute exacerbations of underlying condition within the last 12 months (requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
• Patients with known HIV infection. Testing for HIV is not required for study screening: 1) CD4+ count\<350 cells/uL; or 2) had AIDS-defining opportunistic infections \< 12 months
• Known active hepatitis B (chronic or acute) or hepatitis C infection. Testing for hepatitis is not required for study screening:
• i) Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HbsAg\] test and a NEGATIVE anti-HBc \[antibody to hepatitis B core antigen\] antibody test). Patient is eligible if anti-HBc is POSITIVE, but should sample for HBV DNA and referral to virologist to monitor for HBV reactivation ii) Patients with positive for hepatitis C virus (HCV) antibody and have positive polymerase chain reaction (PCR) for HCV RNA.
• Severe infections within 4 weeks prior to study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Signs or symptoms of infection within 2 weeks prior to study treatment per treating physician and PI judgement.
• Concurrent oral or IV antibiotics within 5 days prior to study treatment
• \* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are allowed and eligible so long as the antibiotic is not prohibited with the study medication (See Tables 8).
• Major surgical procedure within 28 days prior to study treatment or anticipation of need for a major surgical procedure during the course of the study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celcuity Inc: collaborator
• Novartis: collaborator
• Puma Biotechnology, Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

neratinib; capmatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Rachel M. Layman, MD
• Organization: M D Anderson Cancer Center

rlayman@mdanderson.org

713) 745-8401

Study Officials

• Rachel Layman

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 17, 2022
• Study Start: August 18, 2022
• Primary Completion: November 19, 2024
• Study Completion: November 19, 2024
• Last Updated: June 11, 2025
• Results First Posted: May 15, 2025

Record last verified: 2025-04

Locations

US (1)