A Phase 1a/1b Multicenter, Open-label Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of PLN-101095 as Monotherapy and in Combination With Pembrolizumab in Adult Participants With Advanced or Metastatic Solid Tumors Who Have Disease Progression While on Pembrolizumab

This is a Phase 1a/1b, dose-escalation/expansion, consecutive-cohort, open-label study to evaluate the safety, tolerability, PK, PD, and preliminary evidence of antitumor activity of PLN-101095 in combination with pembrolizumab (the study treatment regimen) in adult participants with advanced or metastatic solid tumors for which pembrolizumab is indicated but have documented disease progression (refractory \[primary resistance\]) or relapsed \[secondary resistance\]) after at least 3 months from the start of treatment with pembrolizumab. The study will consist of 2 main parts: * Part 1: Consecutive dose-escalation cohorts using a Bayesian optimal interval (BOIN) dose escalation design * Part 2: Dose-expansion cohorts using Simon's 2-stage design

Overview

PLN-101095 is an investigational oral cancer drug being studied in people whose advanced solid tumors resisted prior immune checkpoint inhibitor treatment. In an ongoing phase 1 study, patients received PLN-101095 alone for 14 days, then continued it with pembrolizumab. The available human results are preliminary and come from a 16-patient dose-escalation study, not a randomized comparison. (aacrjournals.org)

Mechanism of action

PLN-101095 inhibits the integrins αvβ8 and αvβ1, which help activate transforming growth factor–β (TGF-β) in the tumor microenvironment. Blocking that activation is intended to reduce immune suppression and improve T-cell activity. This rationale is supported by preclinical experiments, but its clinical benefit remains under investigation. (aacrjournals.org)

Efficacy

Among 10 patients with secondary resistance to prior checkpoint inhibitors treated at doses of at least 1,000 mg twice daily, investigators reported one complete response and three partial responses with PLN-101095 plus pembrolizumab—four responses in 10 patients, or 40%, in this selected subgroup. One partial response was reported as unconfirmed in the company’s interim disclosure. These small, uncontrolled results cannot establish how much benefit PLN-101095 adds to pembrolizumab. (aacrjournals.org)

Safety

In the 16-patient study, the most common treatment-emergent events were grade 1–2 rash (50%), anemia (18.8%), and diarrhea (18.8%). Five serious adverse events occurred; investigators attributed two to PLN-101095: keratoacanthoma and immune-mediated hepatitis. The hepatitis was the study’s only reported dose-limiting toxicity. Safety remains uncertain with such limited exposure. (aacrjournals.org)

Further reading

• 2026 AACR phase 1 results abstract (aacrjournals.org)
• 2026 ASCO abstract describing planned expansion cohorts (asco.org)
• Preclinical mechanism-of-action poster (pliantrx.com)

Last updated: Sep 2026

Inclusion Criteria:

1. Has histologically or cytologically confirmed advanced solid tumor

2. Has an advanced or metastatic solid tumor (for which pembrolizumab is indicated) and have evidence of disease progression after treatment with pembrolizumab.

3. At least 1 measurable lesion, as defined by RECIST v1.1

4. Estimated survival of ≥3 months

5. No effective therapeutic options available (eg, has received standard of care or is intolerant of, refuses, or is not eligible for standard of care antineoplastic therapy)

Exclusion Criteria:

1. Any immune-related medical conditions that would put participants at greater risk when receiving pembrolizumab

2. Previous treatment with pembrolizumab \<21 days prior to the first dose of combination therapy of pembrolizumab and PLN-101095

3. Received an immunotherapy other than pembrolizumab in the last 4 weeks prior to the first dose of PLN-101095

4. Received radiotherapy (RT) within 1 week for palliative bone-directed therapy and 4 weeks for all other types, prior to the first dose of PLN-101095

5. Received chemotherapy or other targeted therapies within 2 weeks prior to the first dose of PLN-101095

6. Received a cell therapy within the last 12 months prior to the first dose of PLN-101095

7. Known active central nervous system (CNS) metastases (brain and/or leptomeningeal metastases)

8. Pregnant or lactating female participant