Carcinoma, Non-Small-Cell LungPhase 1NCT05544929
A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers
A Phase 1 study testing KFA115 and pembrolizumab in people with Carcinoma, Non-Small-Cell Lung and Cutaneous Melanoma, run by Novartis Pharmaceuticals at 18 sites in 12 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Cutaneous Melanoma, Carcinoma, Renal Cell
- What is being tested?
- KFA115 and pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 18 sitesin 12 countries
- Study dates
- 26 Oct 2022to 5 Oct 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
18 sites in 12 countries.
18 sites in 12 countries
United States5 sites
Massachusetts General Hospital .
Boston, Massachusetts, 02114
Massachusetts General Hospital
Boston, Massachusetts, 02114
SCRI Oncology Partners
Nashville, Tennessee, 37203
NYU School of Medicine
New York, New York, 10015
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
China2 sites
Novartis Investigative Site
Beijing, 100036
Novartis Investigative Site
Guangzhou, Guangdong, 510080
Germany2 sites
Novartis Investigative Site
Dresden, Saxony, 01307
Novartis Investigative Site
Essen, 45147
About this study
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
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.
Read the 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.
- Conditions
- Carcinoma, Non-Small-Cell Lung, Cutaneous Melanoma, Carcinoma, Renal Cell, Carcinoma, Ovarian Epithelial, Nasopharyngeal Carcinoma, Carcinoma, Thymic
- Being tested
- KFA115, pembrolizumab
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Melanoma, Carcinoma, Renal Cell, Carcinoma, Ovarian Epithelial, Nasopharyngeal Carcinoma, Thymoma, Anus Neoplasms, Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KFA115Drug
Also called NVP-KFA115
Immunomodulatory agent
pembrolizumabDrug
Also called Keytruda
Anti-PD-1 antibody
| Study group | Role | What they receive |
|---|---|---|
| Single-agent KFA115 | Experimental | KFA115 monotherapy Receives: Drug: KFA115 |
| KFA115 run-in (1 cycle) + pembrolizumab | Experimental | 1-cycle KFA115 run-in followed by addition of pembrolizumab Receives: Drug: KFA115; Drug: pembrolizumab |
| KFA115 + pembrolizumab | Experimental | KFA115 + pembrolizumab combination given concurrently Receives: Drug: KFA115; Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days
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
Measured: 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
Measured: 35 months
Frequency of dose interruptions, reductions
Number of dose interruptions of KFA115 and pembrolizumab, and number of dose reductions of KFA115
Measured: 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
Measured: 35 months
Secondary outcomes (9)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 35 months
Area under the concentration time curve (AUC) of KFA115 or pembrolizumab
Area under the concentration time curve
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2022
- Study start26 Oct 2022
- Primary completion5 Oct 2027 (estimated)
- Study completion5 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05544929
- Sponsor's protocol ID
- CKFA115A12101
- Other IDs
- 2022-502381-25
- Status last verified
- Oct 2026
- First submitted
- 8 Sep 2022
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No