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

A Phase I, Open-label, Multi-center Study of KFA115 as a Single Agent and in Combination With Pembrolizumab in Patients With Select Advanced Cancers

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Nasopharyngeal Carcinoma; Carcinoma, Ovarian Epithelial; Mesothelioma; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Anal Cancer; Cutaneous Melanoma; Esophagogastric Cancer; Carcinoma, Thymic; High Microsatellite Instability Colorectal Carcinoma
• Intervention / Treatment: Drug: KFA115; Drug: pembrolizumab

Detailed Description

This is a phase I, open-label, multi-center study of KFA115 as a single agent and in combination with pembrolizumab. The study consists of a dose escalation part, followed by dose expansion part(s) for single-agent KFA115 and KFA115 in combination with pembrolizumab. The escalation parts will characterize safety and tolerability. After the determination of the maximum tolerated dose (MTD) / recommended dose (RD), the dose expansion parts will assess the preliminary anti-tumor activity in defined patient populations and further assess the safety and tolerability at MTD/RD.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• China
  • Beijing, China, 100036
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Novartis Investigative Site
• France
  • Lyon, France, 69373
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Novartis Investigative Site
• Italy
  • MI
    • Milan, MI, Italy, 20133
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41124
      • Novartis Investigative Site
• Japan
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104 0045
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 03080
    • Novartis Investigative Site
• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital .
  • New York
    • New York, New York, United States, 10015
      • NYU School of Medicine
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-agent KFA115; KFA115 monotherapy	Drug: KFA115; Immunomodulatory agent; Other Names: NVP-KFA115
Experimental: KFA115 run-in (1 cycle) + pembrolizumab; 1-cycle KFA115 run-in followed by addition of pembrolizumab	Drug: KFA115; Immunomodulatory agent; Other Names: NVP-KFA115; Drug: pembrolizumab; Anti-PD-1 antibody; Other Names: Keytruda
Experimental: KFA115 + pembrolizumab; KFA115 + pembrolizumab combination given concurrently	Drug: KFA115; Immunomodulatory agent; Other Names: NVP-KFA115; Drug: pembrolizumab; Anti-PD-1 antibody; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response (BOR) per RECIST v1.1	BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence	35 months
Progression free survival (PFS) per RECIST v1.1	PFS is defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause	35 months
Duration of response (DOR) per RECIST v1.1	DOR is defined as the time from the date of the first documented response (CR or PR) to the date of the first documented progression as per RECIST v1.1 or death due to underlying cancer	35 months
Time to progression (TTP) per RECIST v1.1	TTP is defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer	35 months
Area under the concentration time curve (AUC) of KFA115 or pembrolizumab	Area under the concentration time curve	During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Peak plasma or serum concentration (Cmax) of KFA115 or pembrolizumab	The maximum (peak) observed plasma or serum drug concentration after single dose administration	During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Minimum plasma or serum concentration (Cmin) of KFA115 or pembrolizumab	The minimum observed plasma or serum drug concentration reached during the time interval between two dose administrations	During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Time to reach peak plasma or serum concentration (Tmax) of KFA115 or pembrolizumab	The time to reach maximum (peak) plasma or serum drug concentration after single dose administration	During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Elimination half-life (T1/2) of KFA115 or pembrolizumab	The elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve	During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: September 8, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: January 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; NSCLC; Colorectal cancer; Rectal cancer; Advanced cancer; Lung cancer; Skin Cancer; Kidney cancer; Renal cancer; TNBC; HNSCC; Triple Negative Breast Cancer; Renal cell carcinoma; Head and neck cancer; Esophageal cancer; CRC; NPC; Mesothelioma; Colon cancer; Nasopharyngeal carcinoma; Advanced solid malignancies; Anal cancer; SCCHN; Rectal neoplasms; Thymic carcinoma; RCC; Non-small-cell lung cancer; Squamous cell carcinoma of the head and neck; Epithelial ovarian cancer; Nasopharyngeal Neoplasms; Ovarian carcinoma; Cutaneous melanoma; Malignant Skin Cancer; Clear cell carcinoma; Cancer of the ovaries; Female reproductive cancer; Thymic tumor; Cancer of throat; Bowel cancer; Cancer of the colon and rectum; High microsatellite instability colorectal carcinoma; MSI-H CRC; NVP-KFA115
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Stomatognathic Diseases; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Rectal Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Esophageal Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Adenoma; Neoplasms, Mesothelial; Skin Diseases; Breast Diseases; Lymphatic Diseases; Urologic Neoplasms; Carcinoma; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nevi and Melanomas; Carcinoma, Squamous Cell; Neoplasms, Complex and Mixed; Breast Neoplasms; Anus Diseases; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Nasopharyngeal Carcinoma; Carcinoma, Ovarian Epithelial; Squamous Cell Carcinoma of Head and Neck; Neoplasms; Rectal Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Esophageal Neoplasms; Ovarian Neoplasms; Mesothelioma; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms; Intestinal Neoplasms; Nasopharyngeal Neoplasms; Melanoma; Triple Negative Breast Neoplasms; Kidney Neoplasms; Adenocarcinoma, Clear Cell; Skin Neoplasms; Thymus Neoplasms; Anus Neoplasms; Thymoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: CKFA115A12101; 2022-502381-25 (Registry Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No