Clinical trial NCT05544929: A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Cutaneous Melanoma
Carcinoma, Renal Cell
Carcinoma, Ovarian Epithelial
Nasopharyngeal Carcinoma
Carcinoma, Thymic
Anal Cancer
Mesothelioma
Esophagogastric Cancer
High Microsatellite Instability Colorectal Carcinoma
Squamous Cell Carcinoma of Head and Neck
Triple Negative Breast Neoplasms
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-09-19
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of single-agent KFA115 (dose escalation only)
timeFrame: 28 days
measure: Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of KFA115 in combination with pembrolizumab (dose escalation only)
timeFrame: 28 days
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 35 months
measure: Frequency of dose interruptions, reductions
timeFrame: 35 months
measure: Dose intensity
timeFrame: 35 months
Secondary outcomes:
measure: Best overall response (BOR) per RECIST v1.1
timeFrame: 35 months
measure: Progression free survival (PFS) per RECIST v1.1
timeFrame: 35 months
measure: Duration of response (DOR) per RECIST v1.1
timeFrame: 35 months
measure: Time to progression (TTP) per RECIST v1.1
timeFrame: 35 months
measure: Area under the concentration time curve (AUC) of KFA115 or pembrolizumab
timeFrame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
measure: Peak plasma or serum concentration (Cmax) of KFA115 or pembrolizumab
timeFrame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
measure: Minimum plasma or serum concentration (Cmin) of KFA115 or pembrolizumab
timeFrame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
measure: Time to reach peak plasma or serum concentration (Tmax) of KFA115 or pembrolizumab
timeFrame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
measure: Elimination half-life (T1/2) of KFA115 or pembrolizumab
timeFrame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital .
state: Massachusetts
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Beijing
country: China
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: