Clinical Trial Finder

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

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.

Arms

Experimental: Single-agent KFA115

KFA115 monotherapy

Experimental: KFA115 run-in (1 cycle) + pembrolizumab

1-cycle KFA115 run-in followed by addition of pembrolizumab

Experimental: KFA115 + pembrolizumab

KFA115 + pembrolizumab combination given concurrently

Interventions

Drug: - KFA115

Immunomodulatory agent

Drug: - pembrolizumab

Anti-PD-1 antibody