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The integrin αvβ8 and αvβ1 inhibitorPLN-101095 in combination with pembrolizumab (Keytruda) was generally well tolerated and showed early efficacy signals in patients with immune checkpoint inhibitor–refractory advanced solid tumors, according to data from an ongoing phase 1a/b trial (NCT06270706) .1
Interim findings from the study demonstrated that patients who received pembrolizumab plus oral PLN-101095 administered at the highest dose of 1000 mg twice daily (cohort 3; n = 6) achieved an overall response rate (ORR) of 50%.2 All responses were confirmed partial responses (PRs), and the other 3 patients experienced unconfirmed disease progression.1,2
In cohort 3, a patient with non–small cell lung cancer experienced a confirmed PR with a 74% reduction in tumor size at week 18, with the initial PR observed at week 10.1 Another patient in this cohort with cholangiocarcinoma achieved a confirmed PR with a 48% reduction in tumor size at week 42; the initial PR was reported at week 34. The final responder was a patient with melanoma who achieved a confirmed PR with a 42% reduction in tumor size at week 27 and an initial response observed at week 18.
In terms of safety, any-grade treatment-emergent adverse effect (TEAEs) across cohorts 1, 2, and 3 (n = 9) occurred at a rate of 66.7%.2 TEAEs during the monotherapy period (44.4%), TEAEs leading to discontinuation of PLN-101095 (11.1%), grade 3 or higher TEAEs (33.3%), and serious TEAEs (33.3%) were all reported. TEAEs occurring in at least 2 patients consisted of rash (33.3%), fatigue (22.2%), and squamous cell carcinoma of skin/keratoacanthoma (22.2%).
“We are encouraged by these early responses given the refractory nature of the patient population enrolled in this trial,” Éric Lefebvre, MD, chief medical officer of Pliant Therapeutics, stated in a news release.1 “We look forward to sharing the final results from this trial in the future.”
The open-label study enrolled patients with histologically or cytologically confirmed advanced or metastatic solid tumors for which pembrolizumab was indicated who had evidence of disease progression following treatment with the agent.3 Patients were also required to have at least 1 measurable lesion per RECIST 1.1 criteria, a life expectancy of at least 3 months, and no effective available therapeutic options.
Patients in cohorts 1 (n = 1), 2 (n = 2), and 3 received oral PLN-101095 monotherapy at doses of 250 mg, 500 mg, or 1000 mg, respectively, twice daily for the first 14 days of treatment.2 The first dose of intravenous pembrolizumab was administered on day 15, and combination therapy continued until week 10. The dose-limiting toxicity (DLT) period began no earlier than day 35. Pembrolizumab was given at 200 mg every 3 weeks in all patients.1
The primary end points were the incidences of TEAEs, serious AEs, and DLTs.3 Secondary end points included ORR, disease control rate, and pharmacokinetic measures.
Additional data from the trial showed that the patient treated in cohort 1 achieved stable disease (SD).2 One patient each in cohort 2 experienced SD and unconfirmed disease progression.
Regarding safety, the patient in cohort 1 experienced a TEAE during the monotherapy period, a serious TEAE, and a grade 3 or higher TEAE. One patient in cohort 2 experienced an any-grade TEAE. In cohort 3, patients experienced any-grade TEAEs (66.7%), TEAEs during the monotherapy period (50.0%), TEAEs leading to discontinuation of PLN-101095 (16.7%), grade 3 or higher TEAEs (33.3%), and serious TEAEs (33.3%).
The study in presently enrolling patients to the fourth of 5 potential cohorts, which is examining PLN-101095 at a dose of 1000 mg 3 times per day.1
### **References**
1. Pliant Therapeutics announces interim phase 1 data for PLN-101095 in patients with immune checkpoint inhibitor-refractory advanced solid tumors. News release. Pliant Therapeutics. March 17, 2025. Accessed March 21, 2025. https://ir.pliantrx.com/news-releases/news-release-details/pliant-therapeutics-announces-interim-phase-1-data-pln-101095
2. PLN-101095 phase 1 trial interim results. Pliant Therapeutics. March 17, 2025. Accessed March 21, 2025. https://ir.pliantrx.com/static-files/8273c374-cee9-435d-ad20-173b714c857b
3. A phase 1 study of PLN-101095 in adults with advanced or metastatic solid tumors. ClinicalTrials.gov. Updated June 12, 2024. Accessed March 21, 2025. https://clinicaltrials.gov/study/NCT06270706