A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers

NCT05544929 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CKFA115A121012022-502381-25
• Study Type: interventional
• Target: 126
• Locations: 12 countries
• Sites: 19

Brief Summary

The purpose of this study is to characterize the safety and tolerability of KFA115 and KFA115 in combination with pembrolizumab in patients with select advanced cancers, and to identify the maximum tolerated dose and/or recommended dose.

Conditions

Cutaneous Melanoma; Carcinoma, Renal Cell; Carcinoma, Ovarian Epithelial; Nasopharyngeal Carcinoma; Carcinoma, Thymic; Anal Cancer; Mesothelioma; Esophagogastric Cancer; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; High Microsatellite Instability Colorectal Carcinoma

Keywords

Lung cancer; Non-small-cell lung cancer; NSCLC; Malignant Skin Cancer; Skin Cancer; Cutaneous melanoma; Renal cell carcinoma; RCC; Kidney cancer; Renal cancer; Clear cell carcinoma; Cancer of the ovaries; Female reproductive cancer; Ovarian carcinoma; Epithelial ovarian cancer; Nasopharyngeal Neoplasms; Nasopharyngeal carcinoma; NPC; Thymic carcinoma; Thymic tumor; Rectal cancer; Rectal neoplasms; Esophageal cancer; Cancer of throat; Colon cancer; Colorectal cancer; Bowel cancer; Cancer of the colon and rectum; High microsatellite instability colorectal carcinoma; CRC; MSI-H CRC; Advanced solid malignancies; Head and neck cancer; HNSCC; SCCHN; Squamous cell carcinoma of the head and neck; Cancer; Advanced cancer; NVP-KFA115; Triple Negative Breast Cancer; TNBC; Mesothelioma; Anal cancer

Outcome Measures

Primary Outcomes (5)

• Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of single-agent KFA115 (dose escalation only)

  A DLT is defined as an adverse event or abnormal laboratory value that occurs during the DLT evaluation period where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications and meets the criteria defined in the study protocol

  28 days

• Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of KFA115 in combination with pembrolizumab (dose escalation only)

  A DLT is defined as an adverse event or abnormal laboratory value that occurs during the DLT evaluation period where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications and meets the criteria defined in the study protocol

  28 days

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  Incidence and severity of adverse events and serious adverse events, including changes in laboratory values, vital signs, and electrocardiograms qualifying and reported as AEs

  35 months

• Frequency of dose interruptions, reductions

  Number of dose interruptions of KFA115 and pembrolizumab, and number of dose reductions of KFA115

  35 months

• Dose intensity

  Dose intensity of KFA115 and pembrolizumab is defined as the ratio of actual cumulative dose received and actual duration of exposure

  35 months

Secondary Outcomes (9)

• Best overall response (BOR) per RECIST v1.1

  35 months

• Progression free survival (PFS) per RECIST v1.1

  35 months

• Duration of response (DOR) per RECIST v1.1

  35 months

• Time to progression (TTP) per RECIST v1.1

  35 months

• Area under the concentration time curve (AUC) of KFA115 or pembrolizumab

  During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab

Study Arms (3)

Single-agent KFA115

EXPERIMENTAL

KFA115 monotherapy

Drug: KFA115

KFA115 run-in (1 cycle) + pembrolizumab

EXPERIMENTAL

1-cycle KFA115 run-in followed by addition of pembrolizumab

Drug: KFA115; Drug: pembrolizumab

KFA115 + pembrolizumab

EXPERIMENTAL

KFA115 + pembrolizumab combination given concurrently

Drug: KFA115; Drug: pembrolizumab

Interventions

KFA115 DRUG

Immunomodulatory agent

Also known as: NVP-KFA115

KFA115 + pembrolizumab; KFA115 run-in (1 cycle) + pembrolizumab; Single-agent KFA115

pembrolizumab DRUG

Anti-PD-1 antibody

Also known as: Keytruda

KFA115 + pembrolizumab; KFA115 run-in (1 cycle) + pembrolizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-small cell lung cancer with historic PD-L1 ≥ 1%, as determined locally using a clinically accepted assay. Patients must have experienced benefit from previous anti-PD(L)1-containing therapy for at least 4 months based on investigator-assessed disease stability or response prior to developing documented disease progression. Patients must have also received prior platinum-based chemotherapy, either in combination or in sequence with anti-PD-(L)1, unless patient was ineligible to receive such treatment.
• Renal cell carcinoma, clear cell histology, previously treated with anti-PD(L)1-containing therapy and a VEGF targeted therapy as monotherapy or in combination. Patients should have documented disease progression following anti-PD(L)1-containing therapy.
• Cutaneous melanoma, previously treated with anti-PD(L)1-containing therapy. Patients should have documented disease progression following anti-PD(L)1-containing therapy. Patients with BRAF V600-mutant melanoma must have also received prior therapy with a BRAF V600 inhibitor, with or without a MEK inhibitor.
• Ovarian cancer, high-grade serous histology, naïve to anti-PD(L)1 therapy, must have received one prior systemic therapy in platinum-resistant setting.
• Nasopharyngeal carcinoma, non-keratinizing locally advanced recurrent or metastatic. Depending on the study arm, patients may be naïve to anti-PD(L)1 therapy, or previously treated with platinum-based chemotherapy with or without anti-PD-(L)1.
• Locally advanced unresectable or metastatic triple negative breast cancer, ovarian cancer (high-grade serous histology), anal cancer (squamous), MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC.
• Locally advanced unresectable or metastatic anal cancer (squamous), thymic carcinoma, MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC, all naïve to anti-PD(L)1 therapy and for whom anti PD(L)1 therapy is not available.
• Triple negative breast cancer with historic PD-L1 CPS ≥ 1%, must have received at least one line of chemotherapy. In addition, these patients must have previously received sacituzumab govitecan, and in the case of a BRCA mutation a PARP inhibitor, if these treatments are locally approved and accessible to the patient.

You may not qualify if:

• Impaired cardiac function or clinically significant cardiac disease.
• Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of study.
• History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
• Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur may be considered. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
• Any evidence of interstitial lung disease (ILD) or pneumonitis, or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
• Patients who discontinued prior anti-PD-(L)1 therapy due to an anti-PD-(L)1-related toxicity (applicable to the KFA115 in combination with pembrolizumab treatment arms).
• Patients with symptomatic peripheral neuropathy limiting instrumental activities of daily living.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (19)

Massachusetts General Hospital .

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

NYU School of Medicine

New York, New York, 10015, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Dresden, Saxony, 01307, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hong Kong, 999077, Hong Kong

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Modena, MO, 41124, Italy

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Carcinoma, Renal Cell; Carcinoma, Ovarian Epithelial; Nasopharyngeal Carcinoma; Thymoma; Anus Neoplasms; Mesothelioma; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Lung Neoplasms; Skin Neoplasms; Kidney Neoplasms; Adenocarcinoma, Clear Cell; Ovarian Neoplasms; Nasopharyngeal Neoplasms; Thymus Neoplasms; Rectal Neoplasms; Esophageal Neoplasms; Colonic Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Head and Neck Neoplasms; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Complex and Mixed; Lymphatic Diseases; Hemic and Lymphatic Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Adenoma; Neoplasms, Mesothelial; Carcinoma, Squamous Cell; Breast Neoplasms; Breast Diseases; Esophageal Diseases; Colonic Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 8, 2022
• First Posted: September 19, 2022
• Study Start: October 26, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); CN (2); FR (1); KR (1); TW (1); CA (1); JP (1); ES (1); US (5); SG (1); HK (1); IT (2)