Trial results for a Phase 1b study (NCT03236935) investigating L-NMMA in combination with pembrolizumab were posted on ClinicalTrials.gov on 2026-04-09. The study, which included participants with various advanced solid tumors and lymphomas, identified a maximum tolerated dose (MTD) of 20 mg/kg for L-NMMA when used with pembrolizumab.
Background
Pembrolizumab (Keytruda) is an established immunotherapy. This study explored its combination with NG-monomethyl-L-arginine (L-NMMA) in participants with advanced cancers including melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma (cHL), and urothelial carcinoma, among others. The trial aimed to test the safety of this combination.
Trial design
The Phase 1b study (NCT03236935) was a safety trial that enrolled 12 participants. It investigated the safety of L-NMMA and pembrolizumab together in participants with various advanced malignancies, including melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, classical Hodgkin lymphoma, urothelial carcinoma bladder, cervical cancer, esophageal cancer, gastric cancer, hepatocellular carcinoma, merkel cell carcinoma, primary mediastinal large B-cell lymphoma, renal cell carcinoma, small cell lung cancer, and microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) cancer.
Key results
The trial identified the Maximum Tolerated Dose (MTD) for L-NMMA in combination with pembrolizumab as 20 mg/kg. The Recommended Phase 2 Dose (RP2D) of L-NMMA in combination with pembrolizumab was also determined to be 20 mg/kg.
Regarding Dose-limiting Toxicities (DLTs) and Other Adverse Events, at L-NMMA Dose Level 0 (15.0 mg/kg), the number of participants experiencing these events was observed as 3 participants, 1 participant, 0 participants, and 1 participant across different measurements. At L-NMMA Dose Level 1 (20 mg/kg), the number of participants experiencing these events was observed as 6 participants, 3 participants, 0 participants, and 3 participants across different measurements.
For antitumor activity, 1 participant in the L-NMMA Dose Level 0 (15.0 mg/kg) group showed antitumor activity, and 1 participant in the L-NMMA Dose Level 1 (20 mg/kg) group also showed antitumor activity.
What this means
The determination of a Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of 20 mg/kg for L-NMMA in combination with pembrolizumab is a critical step for the continued development of this therapeutic regimen. These findings establish a dosage for future studies, which can now proceed to further evaluate efficacy and safety in a larger patient population. The observed antitumor activity in a small number of participants, even in this early phase, suggests a potential for clinical benefit that warrants further investigation.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03236935, titled "Phase Ib of L-NMMA and Pembrolizumab," were posted on 2026-04-09 on clinicaltrials.gov.