NP-G2-044 Elicits Durable Responses, Tumor Control in Advanced Solid Tumors

Phase 2 study results revealed NP-G2-044 plus standard of care anti–PD-1 therapy indicated treatment exhibited responses across at least 7 cancer types.

NP-G2-044 plus standard of care (SOC) anti–PD-1 therapy elicited durable responses and tumor control in patients with advanced solid tumors who experienced progression following treatment with prior anti–PD-1 therapy, according to a news release from the drug’s developer, Novita Pharmacueticals.¹

Findings from a multicenter phase 2 study (NCT05023486) evaluating the therapy in patients with solid tumors were exhibited in a poster presentation at the 2025 American Association for Cancer Research Immuno-Oncology (AACR IO) Annual Meeting. Data presented from the trial revealed that among patients treated with NP-G2-044 (n = 45) at the October 2024 data cut off, the objective response rate (ORR) was 21% (95% CI, 9.0%-38.9%), with 3 patients attaining a complete response (CR) including a pathological CR and 4 patients attaining a partial response (PR). The disease control rate (DCR) was 76%.

Results from the presentation also highlighted a CR in a patient with cervical cancer, a target lesion CR in a patient with endometrial cancer, and pathological CRs in patients with pancreatic cancer and gastroesophageal junction adenocarcinoma. Furthermore, PRs were observed in cutaneous squamous cell carcinoma, non–small cell lung cancer, and cholangiocarcinoma. As of data cut-off, 7 patients remain on treatment, with the longest duration of treatment observed at 18+ months in patients with endometrial cancer and pancreatic cancer.

Patients who converted from immune checkpoint inhibition (ICI) non-responsive to ICI response also saw durable responses and tumor control.

"We are very pleased with the findings generated to date in our phase 2 trial of NP-G2-044 both as a monotherapy and in combination with anti-PD-1 ICIs in patients who are ICI-resistant with advanced and metastatic solid tumors," Jillian Zhang, PhD, president and chief scientific officer of Novita Pharmaceuticals, said in the news release.¹ "The strong safety and durable efficacy we have observed with our first-in-class fascin inhibitor further support the simultaneous inhibition of metastasis and enhancement of cancer immunotherapy as a promising and innovative approach in cancer treatment with broad applications for many solid tumors.”

The phase 2 trial enrolled adult patients with advanced solid tumors with an ECOG performance status score of 0 or 1; a life expectancy of more than 6 months; and adequate organ and bone marrow function.² Patients eligible for enrollment were assigned to receive either NP-G2-044 monotherapy or NP-G2-044 in combination with anti–PD-1 therapy.

Those treated received the recommended phase 2 dose (RP2D) of 1600 mg of oral NP-G2-044 once daily for 28-day cycles. Those in the combination arm additionally received SOC anti–PD-1 therapy at a dose and frequency in accordance with the package insert.

The primary end point of the study was ORR. Secondary end points included progression-free survival, metastasis-free survival, overall survival, and safety.

Previous data presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that the median PFS among patients who received the maximum tolerated-RP2D was 20 weeks, with 70% of patients not developing new metastases.³ Additionally, safety data revealed that the most common TEAEs observed with study treatment were diarrhea, fatigue, and nausea.

According to the news release, an amendment to the study to open additional cohorts is ongoing, for the aim of evaluating further solid tumor subtypes. Biomarker exploration will also be included in future analysis to assess response prediction and mechanisms of resistance. Enrollment in a phase 3 study of NP-G2-044 plus anti–PD-1 therapy in platinum-resistant ovarian cancer is set to begin in Q3 2025.

Exclusion criteria included receipt of chemotherapy, radiotherapy, or other investigational agents within 4 weeks or 5 half-lives of first NP-G2-044 dose, unresolved toxicities from previous anti-cancer treatment, and known brain metastases that have not been radiographically or clinically stable 4 or more weeks prior to enrollment.

References

1. Novita presents additional positive data from phase 2 trial of NP-G2-044 in patients with advanced and metastatic solid tumors at AACR IO Annual Meeting. News release. Novita Pharmaceuticals. February 25, 2025. Accessed February 27, 2025. https://tinyurl.com/3er3ez7f
2. NP-G2-044 As monotherapy and combination therapy in patients with advanced or metastatic solid tumor malignancies. ClinicalTrials.gov. Updated February 13, 2025. Accessed February 27, 2025. https://tinyurl.com/5f9w7f4p
3. Tsai FYC, Birrer MJ, Brown JR, et al. A phase 2 clinical trial of first-in-class fascin inhibitor NP-G2-044 as monotherapy and in combination therapy with anti-PD-1 immunotherapy in patients with advanced solid tumor malignancies. J Clin Oncol. 2025;42(suppl 16):3112. doi:10.1200/JCO.2024.42.16_suppl.3112