INCB99280 / Incyte - LARVOL DELTA

Interventional Study of INCB 99280 With Ipilimumab in Participants With Select Solid Tumors (clinicaltrials.gov) - P1 | N=8 | Terminated | Sponsor: Incyte Corporation | Trial completion date: Jul 2026 ➔ Nov 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ Sep 2024; This was a strategic business decision. There were no safety concerns contributing to this decision.

Trial completion date • Trial primary completion date • Trial termination • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Cutaneous Melanoma • Genito-urinary Cancer • Hepatocellular Cancer • Melanoma • Microsatellite Instability • Oncology • Renal Cell Carcinoma • Solid Tumor • HAVCR2 • IL2 • LAG3 • MSI

A Study to Evaluate INCB099280 in Participants With Select Solid Tumors Who Are Immune Checkpoint Inhibitor Naive (clinicaltrials.gov) - P2 | N=73 | Active, not recruiting | Sponsor: Incyte Corporation | Trial completion date: Jan 2027 ➔ Jul 2026 | Trial primary completion date: Jan 2027 ➔ Jul 2026

Checkpoint inhibition • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • MSI • PD-L1

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of increasing oral doses of INCB099280 in healthy adult participants, and the effect of food on pharmacokinetics (ANZCTR) - P1 | N=72 | Completed | Sponsor: Incyte Corporation | Not yet recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor

NETOS: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=182 | Completed | Sponsor: Incyte Corporation | Active, not recruiting ➔ Completed

Trial completion • Cervical Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Merkel Cell Carcinoma • Mesothelioma • Microsatellite Instability • Nasopharyngeal Carcinoma • Oncology • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Urothelial Cancer

NETOS: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=182 | Active, not recruiting | Sponsor: Incyte Corporation | Trial completion date: Oct 2025 ➔ Dec 2024 | Trial primary completion date: Jul 2025 ➔ Aug 2024

Trial completion date • Trial primary completion date • Cervical Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Merkel Cell Carcinoma • Mesothelioma • Microsatellite Instability • Nasopharyngeal Carcinoma • Oncology • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Urothelial Cancer

NETOS: A personalized approach of neoadjuvant therapy, including INCB099280 monotherapy and bladder preservation, for muscle-invasive urothelial bladder carcinoma (MIBC) with ctDNA monitoring (ESMO 2024) - P1 | "Our hypothesis is that INCB099280 can be offered in selected pts as an induction and maintenance therapy instead of RC in pts who achieve a cCR.Trial design: Pts should have a predominant urotelial carcinoma (UC) histology, have a clinical stage T2-T4N0M0 MIBC, be ineligible for or refuse to receive cisplatin-based chemotherapy. The overall sample size Will be of 30 pts. Secondary endpoints will include safety (CTCAE v.5.0), event-free survival, bladder-intact overall survival (OS) and OS (EUCT number: 2024-511029-73-00)."

Circulating tumor DNA • Clinical • Monotherapy • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Incyte drops pair of PD-L1 drugs as part of 2nd pipeline clear-out this year (FierceBiotech) - "The latest list of discontinued assets includes both of Incyte’s oral, small-molecule PD-L1 inhibitors that were being assessed in phase 1 trials. One of these, INCB99280, was being evaluated in an early-stage solid tumor trial, and the biotech had already set out plans for a phase 1/1b trial in KRASG12C-mutated solid tumors in combination with Bristol Myers Squibb’s Krazati. The other scrapped PD-L1 inhibitor, dubbed INCB99318, was also in a phase 1 solid tumor trial. Also on the chopping block are a couple of LAG3 drug candidates. One of these is a LAG-3 monoclonal antibody dubbed INCAGN2385 that was being developed with Agenus. The other was a bispecific anti–PD1 and anti–LAG-3 antibody dubbed INCA32459 that was being developed with Merus and had undergone a phase 1 study in select advanced malignancies....Finally, Incyte has removed a TIM-3 monoclonal antibody dubbed INCAGN2390, which was another product of the Merus collaboration."

Discontinued • Oncology • Solid Tumor

Pre-Transplant INCBB099280 for Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Abramson Cancer Center at Penn Medicine | N=15 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Pre-transplantation • Trial withdrawal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • Transplantation

A Study to Evaluate INCB099280 in Participants With Select Solid Tumors Who Are Immune Checkpoint Inhibitor Naive (clinicaltrials.gov) - P2 | N=73 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=314 ➔ 73

Checkpoint inhibition • Enrollment change • Enrollment closed • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • MSI • PD-L1

A Study to Evaluate INCB099280 in Participants With Advanced Cutaneous Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=63 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=240 ➔ 63

Enrollment change • Enrollment closed • Metastases • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Interventional Study of INCB 99280 With Ipilimumab in Participants With Select Solid Tumors (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=100 ➔ 8

Combination therapy • Enrollment change • Enrollment closed • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Melanoma • Microsatellite Instability • Oncology • Renal Cell Carcinoma • Solid Tumor • HAVCR2 • IL2 • LAG3 • MSI

A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=125 ➔ 6

Combination therapy • Enrollment change • Enrollment closed • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS • MSI

A Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=5 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=145 ➔ 5

Combination therapy • Enrollment change • Enrollment closed • Metastases • Oncology • Solid Tumor

NETOS: A personalized approach of neoadjuvant therapy, including INCB099280 monotherapy and bladder preservation, for muscle-invasive urothelial bladder carcinoma (MIBC) with ctDNA monitoring. (ASCO 2024) - P1 | "Single-agent pembrolizumab, given neoadjuvantly in patients with T2-4N0M0 MIBC, was effective in PURE-01 trial... Pts should have a predominant urothelial carcinoma (UC) histology, have a clinical stage T2-T4N0M0 MIBC, be ineligible for or refuse to receive cisplatin-based chemotherapy...The overall sample size Will be of 30 pts. Secondary endpoints will include safety (CTCAE v.5.0), event-free survival, bladder-intact overall survival (OS) and OS (EUCT number: 2024-511029-73-00)."

Circulating tumor DNA • Clinical • IO biomarker • Monotherapy • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]INCB099280 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=5 | Completed | Sponsor: Incyte Corporation | Active, not recruiting ➔ Completed

Trial completion

A phase 1 study of the small-molecule PD-L1 inhibitor INCB099280 in select advanced solid tumors: Updated safety, efficacy, and pharmacokinetics (PK) results. (ASCO 2024) - P1 | "INCB099280 was generally well tolerated at all doses tested and showed promising antitumor activity. INCB099280 PK was dose proportional up to 800 mg bid, with high variability; steady-state trough exposure exceeded IC90 for ≥300 bid doses. These data support further development of INCB099280 as monotherapy and in combination regimens for solid tumors."

Clinical • IO biomarker • Metastases • P1 data • PK/PD data • Microsatellite Instability • Oncology • Solid Tumor • MSI

Predicine to Present 9 Liquid Biopsy Studies at ASCO 2024 (Predicine Press Release) - "Predicine, Inc...announced today that it will present data from 9 ctDNA studies at ASCO 2024, spotlighting the clinical utility of Predicine’s genomic and epigenomic liquid biopsy solutions for patient selection, disease monitoring, and drug resistance mechanism studies. The forthcoming data represents significant potential for the practical application of Predicine’s cutting-edge liquid biopsy technology in personalized cancer care, clinical trials, and Companion Diagnostic (CDx) development."

Diagnostic • P1 data • Oncology • Solid Tumor

A Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]INCB099280 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed

Incyte to Highlight Data From its Oncology Portfolio at the 2024 ASCO Annual Meeting and EHA2024 Congress (Businesswire) - "Incyte...announced that several abstracts featuring data from its oncology portfolio will be presented at the upcoming 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held May 31 - June 4 in Chicago, and at the European Hematology Association 2024 (EHA2024) Congress held on June 13-16 in Madrid, Spain, and virtually."

Clinical data • Myelofibrosis • Myeloproliferative Neoplasm • Solid Tumor

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=182 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Cervical Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Merkel Cell Carcinoma • Mesothelioma • Microsatellite Instability • Nasopharyngeal Carcinoma • Oncology • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Urothelial Cancer

A Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]INCB099280 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=7 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open

Pre-Transplant INCBB099280 for Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Abramson Cancer Center at Penn Medicine

New P1 trial • Pre-transplantation • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • Transplantation

A Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=145 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Oncology • Solid Tumor

A Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]INCB099280 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=7 | Not yet recruiting | Sponsor: Incyte Corporation

New P1 trial

Two Phase 1 Studies Assessing the Safety and Efficacy of the Small Molecule Oral PD-L1 Inhibitor INCB099280 in Combination with Adagrasib (INCB 99280-204 [Study 204]) or Ipilimumab (INCB 99280-205 [Study 205]) in Adults with Advanced Solid Tumors (ESMO-IO 2023) - P1 | "Recruitment has started for both studies. Table: 159TiP Eligibility criteria and dosing Study INCB 99280-204 INCB 99280-205 Eligibility criteria Part 1 Previously treated KRASG12C-mutant advanced solid tumors (≤45 pts) Unresectable/metastatic cutaneous melanoma or HCC, advanced clear cell RCC, or centrally confirmed MSI-H/dMMR metastatic CRC (≤36 pts) Part 2 Previously treated, KRASG12C inhibitor-naive KRASG12C-mutant advanced NSCLC/ CRC (≤80 pts) Immuno-/systemic tx-naive Unresectable/metastatic HCC or RCC (≤80 pts) Combination drug regimen Adagrasib 400 mg BID Ipilimumab q3w for ≤4 doses, RCC & CRC: 1 mg/kg HCC & melanoma: 3 mg/kg"

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • KRAS • MSI