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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05544929
• Other study ID #: CKFA115A12101
• Secondary ID: 2022-502381-25
• Status: Recruiting
• Phase: Phase 1
• Start date: October 26, 2022
• Est. completion date: February 20, 2026

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: February 20, 2026
• Est. primary completion date: February 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• KFA115
Immunomodulatory agent
• pembrolizumab
Anti-PD-1 antibody

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Toronto	Ontario
Germany	Novartis Investigative Site	Dresden
Hong Kong	Novartis Investigative Site	Shatin New Territories
Italy	Novartis Investigative Site	Milano	MI
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Taiwan	Novartis Investigative Site	Taipei
United States	Massachusetts General Hospital .	Boston	Massachusetts
United States	SCRI Oncology Partners Sarah Cannon new location	Nashville	Tennessee
United States	NYU School of Medicine Langone Health	New York	New York
United States	University of Pittsburgh MC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Hong Kong,  Italy,  Japan,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Frequency of dose interruptions, reductions	Number of dose interruptions of KFA115 and pembrolizumab, and number of dose reductions of KFA115	35 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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