A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors

Pliant Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Advanced or Metastatic Solid Tumor

Treatments: Drug: Pembrolizumab; Drug: PLN-101095

Study type: Interventional

Funder types: Industry

Identifiers

NCT06270706

PLN-101095-ONC-101

Details and patient eligibility

About

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 with accelerated titration
• Part 2: Dose-expansion cohorts using Simon's 2-stage design

Enrollment: 124 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Has histologically or cytologically confirmed advanced or metastatic solid tumor
2. Have received ≥12 weeks of continuous anti-PD-1 or anti-PD-L1 treatment administered as monotherapy or in combination with other anticancer therapies
3. Have demonstrated documented prior clinical benefit, defined as CR or PR at any time during treatment, or SD lasting ≥6 months (Part 2 only)
4. Must have subsequently developed radiographic disease progression while receiving anti-PD-1 or anti-PD-L1 treatment or within ≤12 weeks after the last dose of such treatment
5. At least 1 measurable lesion, as defined by RECIST v1.1
6. Estimated survival of ≥3 months
7. Have adequate bone marrow and organ function.
8. A female participant is eligible to participate if she is not pregnant, not breastfeeding

Exclusion criteria

1. Any immune-related medical conditions that would put participants at greater risk when receiving pembrolizumab
2. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
3. Has received prior radiotherapy within 2 weeks for palliative bone-directed therapy and 4 weeks for all other radiotherapy
4. Has undergone major surgery within 4 weeks prior to the first dose of study treatment or has not adequately recovered from surgery or related complications
5. Has a diagnosis of immunodeficiency or use of systemic steroids >10 mg/day
6. Has an active autoimmune disease that has required systemic treatment in the past 2 years
7. Has known active CNS metastases (brain and/or leptomeningeal metastases)
8. Has significant cardiac disease
9. Has an active infection requiring systemic therapy (including uncontrolled HIV, Hepatitis B and C)
10. Has received a live or live-attenuated vaccine within 30 days or a non-live vaccine within 7 days prior to the first dose of PLN-101095

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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124 participants in 8 patient groups

Part 1 Dose Escalation - 250 mg BID

Experimental group

Description:

Cohort 1 PLN-101095 250 mg BID in combination with pembrolizumab in participants with solid tumors

Treatment:

Drug: PLN-101095

Drug: Pembrolizumab

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Part 1 Dose Escalation - 500 mg BID

Experimental group

Description:

PLN-101095 500 mg BID in combination with pembrolizumab in participants with solid tumors

Treatment:

Drug: PLN-101095

Drug: Pembrolizumab

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Part 1 Dose Escalation - 1000 mg BID

Experimental group

Description:

PLN-101095 1000 mg BID in combination with pembrolizumab in participants with solid tumors

Treatment:

Drug: PLN-101095

Drug: Pembrolizumab

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Part 1 Dose Escalation - 1000 mg TID

Experimental group

Description:

PLN-101095 1000 mg TID in combination with pembrolizumab in participants with solid tumors

Treatment:

Drug: PLN-101095

Drug: Pembrolizumab

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Part 1 Dose Escalation - 2000 mg BID

Experimental group

Description:

PLN-101095 2000 mg BID in combination with pembrolizumab in participants with solid tumors

Treatment:

Drug: PLN-101095

Drug: Pembrolizumab

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Part 2 Dose Expansion - NSCLC

Experimental group

Description:

PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Non-small cell lung cancer (NSCLC)

Treatment:

Drug: PLN-101095

Drug: Pembrolizumab

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Part 2 Dose Expansion - ccRCC

Experimental group

Description:

PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Clear cell renal cell carcinoma (ccRCC)

Treatment:

Drug: PLN-101095

Drug: Pembrolizumab

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Part 2 Dose Expansion - TMB-high solid tumors

Experimental group

Description:

PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Tumor mutational burden (TMB)-high solid tumors

Treatment:

Drug: PLN-101095

Drug: Pembrolizumab

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095

Drug: PLN-101095