Pliant Therapeutics : Final AACR 2026 PLN10195 Yap

Published: 2026-04-18 13:38:06 ET PLRX

Published on 04/18/2026 at 01:38 pm EDT

Timothy A. Yap, MBBS, PhD, FRCP,1 Andrae Vandross, MD,2 Jenny Amaya-Amaya, MD, MSc,3 Chris N. Barnes, PhD,3 Shuguang Ma, PhD,3 Martin Decaris, PhD,3 Keithryn Nicolas, BS,3 Alexander Spira, MD, PhD, FACP,4 Jacqueline Brown, MD,5 Patricia LoRusso, DO,6 Manish R. Sharma, MD7

1University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2NEXT Oncology, Austin, TX, USA; 3Pliant Therapeutics Inc., South San Francisco, CA, USA; 4NEXT Oncology, Fairfax, VA, USA; 5Winship Cancer Institute of Emory University, Atlanta, GA, USA; 6Yale Cancer Center, New Haven, CT, USA; 7START Center for Cancer Research - Midwest, Grand Rapids, MI, USA

‌I have the following relevant financial relationships to disclose:

Employee of: University of Texas MD Anderson Cancer Center

Consultant for: AbbVie, Acrivon, Adagene, Almac, Aduro, Amphista, Artios, Astex, AstraZeneca, Athena, Atrin, Avenzo, Avoro, Axiom, Baptist Health Systems, Bayer, BeiGene, BioCity Pharma, Blueprint, Boxer, Bristol Myers Squibb, C4 Therapeutics, Calithera, Cancer Research UK, Carrick Therapeutics, Circle Pharma, Clovis, Cybrexa, Daiichi Sankyo, Dark Blue Therapeutics, Diffusion, Duke Street Bio, 858 Therapeutics, EcoR1 Capital, Ellipses Pharma, EMD Serono, Entos, F-Star, Genesis Therapeutics, Genmab, Glenmark, GLG, Globe Life Sciences, GSK, Guidepoint, Ideaya Biosciences, Idience, Ignyta, I-Mab, ImmuneSensor, Impact Therapeutics, Institut Gustave Roussy, Intellisphere, Jansen, Kyn, MEI pharma, Mereo, Merck, Merit, Monte Rosa Therapeutics, Natera, Nested Therapeutics, Nexys, Nimbus, Novocure, Odyssey, OHSU, OncoSec, Ono Pharma, Onxeo, PanAngium Therapeutics, Pegascy, PER, Pfizer, Piper-Sandler, Pliant Therapeutics Inc., Prolynx, Radiopharma Theranostics, Repare, resTORbio, Roche, Ryvu Therapeutics, SAKK, Sanofi, Schrodinger, Servier, Synnovation, Synthis Therapeutics, Tango, TCG Crossover, TD2, Terremoto Biosciences, Tessellate Bio, Theragnostics, Terns Pharmaceuticals, Tolremo, Tome, Thryv Therapeutics, Trevarx Biomedical, Varian, Veeva, Versant, Vibliome, Voronoi Inc, Xinthera, Zai Labs and ZielBio

Grant/Research support: AbbVie, Acrivon, Adagene, Almac, Aduro, Amphista, Artios, Astex, AstraZeneca, Athena, Atrin, Avenzo, Avoro, Axiom, Baptist Health Systems, Bayer, BeiGene, BioCity Pharma, Blueprint, Boxer, Bristol Myers Squibb, C4 Therapeutics, Calithera, Cancer Research UK, Carrick Therapeutics, Circle Pharma, Clovis, Cybrexa, Daiichi Sankyo, Dark Blue Therapeutics, Diffusion, Duke Street Bio, 858 Therapeutics, EcoR1 Capital, Ellipses Pharma, EMD Serono, Entos, F-Star, Genesis Therapeutics, Genmab, Glenmark, GLG, Globe Life Sciences, GSK, Guidepoint, Ideaya Biosciences, Idience, Ignyta, I-Mab, ImmuneSensor, Impact Therapeutics, Institut Gustave Roussy, Intellisphere, Jansen, Kyn, MEI pharma, Mereo, Merck, Merit, Monte Rosa Therapeutics, Natera, Nested Therapeutics, Nexys, Nimbus, Novocure, Odyssey, OHSU, OncoSec, Ono Pharma, Onxeo, PanAngium Therapeutics, Pegascy, PER, Pfizer, Piper-Sandler, Pliant Therapeutics Inc., Prolynx, Radiopharma Theranostics, Repare, resTORbio, Roche, Ryvu Therapeutics, SAKK, Sanofi, Schrodinger, Servier, Synnovation, Synthis Therapeutics, Tango, TCG Crossover, TD2, Terremoto Biosciences, Tessellate Bio, Theragnostics, Terns Pharmaceuticals, Tolremo, Tome, Thryv Therapeutics, Trevarx Biomedical, Varian, Veeva, Versant, Vibliome, Voronoi Inc, Xinthera, Zai Labs and ZielBio

Supported by the NCI Cancer Center Support Grant CA016672 to The University of Texas MD Anderson Cancer Center, Department of Defense grants

W81XWH2210504_BC211174 and W81XWH-21-1-0282_OC200482, V Foundation Scholar Grant VC2020-001 and NIH R01 grant 1R01CA255074

Timothy A. Yap Disclosure Information

SOLID

TUMOR MASS

α β

CD8+ T CELL

V 8

IFN-γ MHCII

Latent TGF-β

αVβ1

× αVβ8

× PLN-101095

REGULATORY T CELL

PLN-101095 is designed to:

Potently block integrin αVβ8- and αVβ1-driven activation of TGF-β locally in the TME

This differs from past strategies of systemically targeting the active TGF-β cytokine, TGF-β receptor kinase or specific isoforms of TGF-β

Selectively enhance T cell IFN-γ effector function

Reduce fibroblast activation and fibrotic tumor stroma

Combine with orthogonal IO approaches like anti-PD-(L)1

Inhibition of integrin αVβ8 and αVβ1 blocks activation of TGF-β to reduce immunosuppression, leading

to a new or reinvigorated cancer immune response2,3

1. Lainé A, et al. Nat Comm. 2021;12:6228; 2. Kothari V, et al. J Immunother Cancer. 2022;10(Suppl 2):Abstract 1352; 3. Kothari V, et al. J Immunother Cancer. 2023;11(Suppl 1):Abstract 464.

CD, cluster of differentiation; IFN, interferon; IO, immuno-oncology; MHC, major histocompatibility complex; PD-(L)1, programmed death (ligand) protein-1; TGF, transforming growth factor; TME, tumor microenvironment.

PLN-101095 Is a Novel, Orally Bioavailable Integrin

αVβ8 and αVβ1 Inhibitor

Anti-PD-(L)1 Nonresponsive Baseline

Gene Signature

High TGF-β

Signature

Low IFN-γ

Signature

PLN-101095 resensitizes tumors

to anti-PD-(L)1

High IFN-γ

Signature

Low TGF-β

Signature

Log2 Fold

-2

POSTN CTHRC1 COL6A3 SERPINE1

MMP9 COL1A1 CYR61 SMAD7 COL1A2 COL3A1 ACTA2

-2

EMT6 tumor model,

PLN-101095 dosed by minipump

(144 mg/kg/day)

Cxcl9

H2-Ab1 H2-DMa

Gzma Prf1 Gzmb Cxcl10 Ifng

Vehicle PLN-101095

+ α-PD-1 + α-PD-1

IFN-γ Gene Signature

By inhibiting TGF-β,

PLN-101095 shifts solid tumors to a high-IFN-γ signature, ICI-responsive state

TGF-β Gene

Signature

Daud A, et al. J Immunother Cancer. 2023;11(Suppl 1):Abstract 714. ICI, immune checkpoint inhibitor.

PLN-101095 Promotes ICI Responsiveness by

Inhibiting TGF-β and Increasing IFN-γ Expression

PLN-101095

combined with pembrolizumab

DAY 1

PLN-101095

monotherapy

DAY 15:

Add pembro

WEEK 10 + EVERY 8 WEEKS:

Assess tumor response

2000 mg BID (n=3)

BOIN

escalation

1000 mg TID (n=4)c

1000 mg BID (n=6)b

500 mg BID (n=2)a

250 mg BID (n=1)

Accelerated

titration

Dose

escalation completed with all doses levels cleared

PLN-101095

monotherapy

Prior exposure to PD-1 therapy with documented PD

Primary or secondary resistance by SITC definition1,d

TEAEs, serious TEAEs and DLTs

Pharmacokinetics

Antitumor activity: ORR, DCR per iRECIST

Changes in blood-based biomarkers

NCT06270706. 1. Kluger H, et al. J Immunother Cancer. 2023;11:e005921.

a One participant discontinued at Day 14 due to PD. b Cohort expanded due to single DLT. c One patient added as part of backfill. d SITC primary resistance: BOR of PD or SD <6 months despite adequate treatment

exposure; secondary resistance: prior CR, PR or SD ≥6 months followed by progression during or after treatment.

BID, twice daily; BOIN, Bayesian optimal interval; BOR, best overall response; CR, complete response; DCR, disease control rate; DLT, dose-limiting toxicity; iRECIST, Immunological Response Evaluation Criteria in Solid Tumors; ORR, objective response rate; PD, disease progression; pembro, pembrolizumab; PR, partial response; SD, stable disease; SITC, Society for Immunotherapy of Cancer; TEAE, treatment-emergent adverse event; TID, three times daily.

Phase 1, Open-Label, Dose-Escalation Study in Patients With Solid Tumors With Prior ICI Resistance

‌Cohort 1

250 mg BID (n=1)

Cohort 2

500 mg BID (n=2)

Cohort 3

1000 mg BID (n=6)

Cohort 4

1000 mg TID (n=4)

Cohort 5

2000 mg BID (n=3)

Total

(n=16)

Age, yeara

70 (70-70)

58 (53-63)

56 (53-63)

48 (41-60)

67 (66-72)

60 (52-68)

Male, n (%)

1 (100)

2 (100)

2 (33.3)

1 (25.0)

2 (66.7)

8 (50.0)

Tumor type, n (%)

NSCLC

1 (100.0)

2 (33.3)

3 (18.8)

Cholangiocarcinoma

1 (16.7)

1 (25.0)

1 (33.3)

3 (18.8)

HNSCC

1 (50.0)

1 (33.3)

2 (12.5)

RCC

1 (50.0)

1 (25.0)

2 (12.5)

Melanoma

1 (16.7)

1 (6.3)

CRC

1 (33.3)

1 (6.3)

Endometrial

1 (16.7)

1 (6.3)

TNBC

1 (16.7)

1 (6.3)

Ovarian CCA

1 (25.0)

1 (6.3)

Anal SCC

1 (25.0)

1 (6.3)

Prior therapy linesa

2 (2-2)

3.5 (3-4)

3.5 (1-4)

3 (1.5-4)

3 (2-4)

ICI secondary resistance, n (%)b

2 (100)

4 (66.7)

3 (75.0)

3 (100)

12 (75.0)

a Median (IQR). b SITC secondary resistance: prior CR, PR or SD ≥6 months followed by progression during or after treatment.

CCA, clear cell adenocarcinoma; CRC, colorectal cancer; HNSCC, head and neck squamous cell carcinoma; IQR, interquartile range; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma; SCC, squamous cell carcinoma; TNBC, triple-negative breast cancer.

Patient Baseline Characteristics

‌n (%)

Cohort 1

250 mg BID (n=1)

Cohort 2

500 mg BID (n=2)

Cohort 3

1000 mg BID (n=6)

Cohort 4

1000 mg TID (n=4)

Cohort 5

2000 mg BID (n=3)

Total

(n=16)

Any TRAE

1 (100)

1 (50)

4 (67)

4 (100)

2 (67)

12 (75)

Grade 3/4a

1 (17)c

1 (6)

Serious

1 (100)b

1 (17)c

2 (13)

Led to discontinuation

1 (17)c

1 (25)d

2 (13)

Most common TRAEs (in >1 participant)

Rashe

1 (50)

2 (33)

2 (50)

1 (33)

6 (38)

Fatigue

2 (33)

2 (13)

Hypomagnesemia

1 (25)

1 (33)

2 (13)

Pruritus

1 (25)

1 (33)

2 (13)

The most common TRAE was rashe

All rashes were grade 1 or 2

One treatment-related rash was reported during the monotherapy period, but otherwise these were primarily observed within 2 days of starting combination treatment

a No Grade 5 TRAEs occurred. b Keratoacanthoma (Grade 2). c Immune-mediated hepatitis (Grade 3), considered a DLT. d Dermatitis bullous (Grade 2). e Includes rash, rash erythematous, rash maculo-papular, dermatitis acneiform and dermatitis bullous.

TRAE, treatment-related adverse event.

PLN-101095 Was Generally Well Tolerated

Time, hours

IC75

100

IC90

1000

IC99

250 mg BID (n=1)

500 mg BID (n=1)

1000 mg BID (n=5)

1000 mg TID (n=4)

2000 mg BID (n=3)

10000

Total PLN-101095 Concentration, ng/mL

‌All participants receiving ≥1000

mg BID maintained IC

coverage over 24 hours,

supporting consistent target engagement

PK profile supports continuous pharmacologic inhibition with BID dosing at steady state

All participants treated with ≥1000 mg BID maintained IC75 coverage over 24 hours,

supporting consistent target engagement

IC75, 75% maximal inhibitory concentration; IC90, 90% maximal inhibitory concentration; IC99, 99% maximal inhibitory concentration; PK, pharmacokinetics.

PLN-101095 Monotherapy Demonstrated

Dose-Ordered Exposure at Day 14

100

−20

−40

−60

−80

−100

1 CR, 2 PRs and

1 unconfirmed PR

Partial response threshold

*†

‌Dose level

Maximum Change From Baseline in Target Tumor, %

1000 mg TID

Tumor type

Ovarian CCA

† Nontarget lesions present (BOR=iPR)

* Confirmed response

Secondary Resistance ≥ 1000 mg BID

Overall study population: 19% ORR | 56% DCR ICI secondary resistance: 30% ORR | 60% DCR

a As of Feb 27, 2026.

Responses Were Observed in Patients With

Secondary ICI Resistance

Time, weeks

* * * *

1 10 18 26 34 42 50 58 66 74 82 90 98 106

−100

†

‡ ‡ †

† †

−40

−60

−80

Partial response threshold

−20

Dose level

2000 mg BID

1000 mg TID

1000 mg BID

500 mg BID

250 mg BID

100

‌Tumor type

Change From Baseline in Sum of Target Diameters, %

† Target lesions nonmeasurable with nontarget lesions present (BOR=iPR)

‡ Target lesions disappeared with nontarget lesions present (BOR=iPR)

* Complete resolution of target and nontarget lesions

Median time on treatment is 19 months for the 3 confirmed objective responders, who had an average maximum tumor reduction of -89%

Data as of Feb 27, 2026. Confirmed objective responders had BOR of iPR or iCR. iCR, complete response per iRECIST; iPR, partial response per iRECIST.

Clinically Significant, Durable Responses Observed

in 3 of 4 iRECIST Responders at Doses ≥1000 mg BID

‌Prior Treatment History

Gemcitabine/Cisplatin

Feb 2019 - Jul 2019

FOLFIRI

Oct 2019 - Jan 2020

Capecitabine

Feb 2019 - Mar 2020

Pembrolizumab

Mar 2021 - Feb 2024

(Confirmed PD)

63-year-old male

Cholangiocarcinoma, 2019

Lynch Syndrome

Prior Hx of CRC, basal and SCC of skin

TL: Left peritoneal implant

Screening

Mar 15, 2024

34 mm

Week 26

Sep 19, 2024

25 mm

Week 66

Jul 1, 2025

12 mm

Week 74

Aug 18, 2025

Courtesy of Dr Manish Sharma. Patient had a confirmed response.

FOLFIRI, folinic acid, fluorouracil and irinotecan; Hx, history; TL, target lesion.

Tumor Shrinkage Over Time - Case #1 (CR)

iRECIST CR (106+ weeks on trial)

‌Prior Treatment History

Pembrolizumab for 35 months (followed by confirmed PD)

RT for metastatic disease in brain and mediastinum

57-year-old female

TMB-H NSCLC adenocarcinoma, 2020

One prior line of treatment

Screening

Oct 24, 2024

SA1: 23.1 mm

SA2: 15.9 mm

Week 2

Nov 18, 2024

SA1: 27.9 mm

SA2: 18.6 mm

Week 10

Jan 15, 2024

SA1: 8.9 mm

SA2: 11.1 mm

T01 - Lymph node

Cervical upper left (Level II)

T02 - Lymph node Supraclavicular

right (Level V)

Courtesy of Dr Alexander Spira. RT, radiotherapy.

Tumor Shrinkage Over Time - Case #2

iRECIST PR (66 weeks on trial)

Responder (n=4)

Nonresponder (n=10)

** P<0.01

* P<0.05

Time, weeks

−25

Combination

Mono-

therapy

Mean (±SE) change over 10 weeks

Change in PD-L1, %

Elevated plasma IFN-γ was observed in responders

Elevated plasma PD-L1 was observed in responders

Time, weeks

2-fold increase over baseline

iPR

300

400

Week 2

Monotherapy

iuPR

600

iPR

Responder (n=4)

Nonresponder (n=10)

** P<0.01

* P<0.05

800

Combination

Mono-

therapy

900

1200

iCR

Mean (±SE) change over 10 weeks

Change in IFN-γ, %

Known to be induced by IFN-γ; higher tumor PD-L1 expression predicts improved response to ICIs1

Increase in IFN-γ during monotherapy may act as a potential biomarker of TGF-β inhibition;

this will be studied further in dose-expansion cohorts

1. Incorvaia l, et al. Adv Ther. 2019;36:2600-2617.

Responders: PR and CR. Nonresponders: SD and PD. One patient with immune-mediated hepatitis and resultant increase in IFN-γ (nonresponder) was excluded from the mean change analyses.

iuPR, unconfirmed partial response per iRECIST.

Clinical Response to PLN-101095 Is Associated With Elevated

Plasma IFN-γ and PD-L1 Levels After 14 Days' Monotherapy

‌PLN-101095 was generally well tolerated in the dose-escalation part of this Phase 1 study, with no new safety concerns emerging when the integrin inhibitor was combined with pembrolizumab

Early signals of antitumor activity were observed in patients with ICI secondary resistance

(ORR, 30%; DCR, 60%) treated with PLN-101095 in combination with pembrolizumab

Circulating IFN-γ may be a potential biomarker for early prediction of treatment response

Dose-expansion cohorts have been initiated in advanced NSCLC, ccRCC and TMB-H cancers

These data for PLN-101095 with pembrolizumab suggest the potential to

meet a high unmet clinical need among patients with secondary ICI resistance, with no new safety concerns

Conclusions

‌Thank you to the patients and their caregivers

This study was sponsored by Pliant Therapeutics, Inc.

Editorial assistance was provided by Samantha Santangelo, PhD, of Nucleus Global and

funded by Pliant Therapeutics Inc.

Disclaimer

Pliant Therapeutics Inc. published this content on April 18, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 18, 2026 at 17:37 UTC.