A Study of Safety and Efficacy of KFA115 Alone and in Combination With Pembrolizumab in Patients With Select Advanced Cancers
- Conditions
- Carcinoma, Renal CellCutaneous MelanomaCarcinoma, Ovarian EpithelialNasopharyngeal CarcinomaCarcinoma, ThymicAnal CancerSquamous Cell Carcinoma of Head and NeckEsophagogastric CancerTriple Negative Breast NeoplasmsCarcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT05544929
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description KFA115 run-in (1 cycle) + pembrolizumab KFA115 1-cycle KFA115 run-in followed by addition of pembrolizumab Single-agent KFA115 KFA115 KFA115 monotherapy KFA115 + pembrolizumab KFA115 KFA115 + pembrolizumab combination given concurrently KFA115 run-in (1 cycle) + pembrolizumab pembrolizumab 1-cycle KFA115 run-in followed by addition of pembrolizumab KFA115 + pembrolizumab pembrolizumab KFA115 + pembrolizumab combination given concurrently
- Primary Outcome Measures
Name Time Method Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) 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
Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of single-agent KFA115 (dose escalation only) 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
Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of KFA115 in combination with pembrolizumab (dose escalation only) 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
Frequency of dose interruptions, reductions 35 months Number of dose interruptions of KFA115 and pembrolizumab, and number of dose reductions of KFA115
Dose intensity 35 months Dose intensity of KFA115 and pembrolizumab is defined as the ratio of actual cumulative dose received and actual duration of exposure
- Secondary Outcome Measures
Name Time Method Duration of response (DOR) per RECIST v1.1 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
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 Area under the concentration time curve
Progression free survival (PFS) per RECIST v1.1 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
Peak plasma or serum concentration (Cmax) of KFA115 or pembrolizumab 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
Time to progression (TTP) per RECIST v1.1 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
Elimination half-life (T1/2) of KFA115 or pembrolizumab 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
Time to reach peak plasma or serum concentration (Tmax) of KFA115 or pembrolizumab 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
Best overall response (BOR) per RECIST v1.1 35 months BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
Minimum plasma or serum concentration (Cmin) of KFA115 or pembrolizumab 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
Trial Locations
- Locations (5)
Massachusetts General Hospital .
🇺🇸Boston, Massachusetts, United States
NYU School of Medicine
🇺🇸New York, New York, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Novartis Investigative Site
🇨🇳Taipei, Taiwan