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Active, Not Recruiting

NCT Number: NCT05544929

A Study of Safety and Efficacy of KFA115 Alone and in Combo 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Carcinoma, Non-Small-Cell Lung Adenocarcinoma Adenocarcinoma, Clear Cell Adenoma Adnexal Diseases Anal Cancer Anus Diseases Anus Neoplasms Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Ovarian Epithelial Carcinoma, Renal Cell Carcinoma, Squamous Cell Carcinoma, Thymic Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Cutaneous Melanoma Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Esophageal Diseases Esophageal Neoplasms Esophagogastric Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Hemic and Lymphatic Diseases High Microsatellite Instability Colorectal Carcinoma Intestinal Diseases Intestinal Neoplasms Kidney Diseases Kidney Neoplasms Lung Diseases Lung Neoplasms Lymphatic Diseases Male Urogenital Diseases Melanoma Mesothelioma Nasopharyngeal Carcinoma Nasopharyngeal Diseases Nasopharyngeal Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Complex and Mixed Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Otorhinolaryngologic Diseases Otorhinolaryngologic Neoplasms Ovarian Diseases Ovarian Neoplasms Pharyngeal Diseases Pharyngeal Neoplasms Rectal Diseases Rectal Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Squamous Cell Carcinoma of Head and Neck Stomatognathic Diseases Thoracic Neoplasms Thymoma Thymus Neoplasms Triple Negative Breast Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Toronto, Ontario, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

KFA115

Drug

Immunomodulatory agent

Other names: NVP-KFA115

Pembrolizumab

Drug

Anti-PD-1 antibody

Other names: Keytruda

Primary outcomes

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

    Time frame: 28 days

    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

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

    Time frame: 28 days

    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

  3. Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

    Time frame: 35 months

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

  4. Frequency of dose interruptions, reductions

    Time frame: 35 months

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

  5. Dose intensity

    Time frame: 35 months

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

Secondary outcomes

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

    Time frame: 35 months

    BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence

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

    Time frame: 35 months

    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

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

    Time frame: 35 months

    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

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

    Time frame: 35 months

    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

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

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

    Area under the concentration time curve

  6. Peak plasma or serum concentration (Cmax) of KFA115 or pembrolizumab

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

    The maximum (peak) observed plasma or serum drug concentration after single dose administration

  7. Minimum plasma or serum concentration (Cmin) of KFA115 or pembrolizumab

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

    The minimum observed plasma or serum drug concentration reached during the time interval between two dose administrations

  8. Time to reach peak plasma or serum concentration (Tmax) of KFA115 or pembrolizumab

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

    The time to reach maximum (peak) plasma or serum drug concentration after single dose administration

  9. Elimination half-life (T1/2) of KFA115 or pembrolizumab

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

    The elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Sep 19, 2022
Registry last updated
Jan 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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