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

More details:

Overview

KFA115 (also referred to as NVP‑KFA115) is a Novartis investigational immunomodulatory agent being studied for advanced solid tumors. A first‑in‑human, open‑label phase 1 trial is evaluating KFA115 as monotherapy and in combination with the PD‑1 inhibitor pembrolizumab across multiple tumor types (including NSCLC with prior benefit on anti‑PD‑(L)1, clear‑cell RCC, and cutaneous melanoma). The study began on October 26, 2022 and remains recruiting, with an estimated completion in 2027. (novartis.com)

Mechanism of action

Publicly available materials from Novartis describe KFA115 as a “novel immunomodulatory agent,” but do not disclose a specific molecular target or mechanism as of the latest updates. (novartis.com)

Clinical development

• Study design: Phase 1, open‑label, multi‑center, dose‑escalation followed by dose‑expansion; arms include KFA115 monotherapy; KFA115 run‑in then addition of pembrolizumab; and concurrent KFA115 plus pembrolizumab. Primary objectives are safety/tolerability and defining the MTD/RD; secondary endpoints include preliminary antitumor activity (RECIST v1.1) and pharmacokinetics. (novartis.com)
• Populations: Enrollment includes selected advanced cancers such as NSCLC (PD‑L1 ≥1% with prior benefit from anti‑PD‑(L)1), clear‑cell RCC, and cutaneous melanoma; additional solid tumors are included in expansion cohorts. (novartis.com)
• Status and timeline: Recruiting; target enrollment ~180; study start October 26, 2022; estimated primary completion and study completion September 1, 2027 (most recent Novartis update August 26, 2025). (novartis.com)

Efficacy

As of the most recent publicly available updates, no efficacy results from human studies of KFA115 have been posted or published. The ongoing phase 1 trial is designed to assess preliminary antitumor activity in expansion cohorts. (novartis.com)

Safety

No human safety results have been publicly reported yet. The current phase 1 study’s primary objective is to characterize safety and tolerability and to identify dose‑limiting toxicities and a recommended dose for further study. (novartis.com)

Further reading

• Novartis clinical trial listing for NCT05544929 (CKFA115A12101). (novartis.com)
• Novartis pipeline entry (Oncology: Solid Tumors) describing KFA115 as a novel immunomodulatory agent. (novartis.com)
• Academic site listing with trial arm structure (NYU Langone Health). (clinicaltrials.med.nyu.edu)

Note: If new conference abstracts or peer‑reviewed publications become available, they should be added; none were identified in the public domain as of August 2025. (novartis.com)

Last updated: Oct 2025

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