134P A phase I study exploring the safety and tolerability of the small molecule PD-L1 inhibitor INCB099318 in select advanced solid tumors
Bibliographic record
Abstract
INCB099318, an oral, programmed death ligand-1 (PD-L1) inhibitor, has shown preliminary efficacy and acceptable safety in an ongoing, Phase 1, open-label, multicenter study in patients with advanced solid tumors (Pinato, et al. SITC 2022). Here we present updated study results. Eligible patients were ≥18 years with ECOG PS ≤1, who had disease progression after available treatment or were ineligible for/without access to standard treatment. In Part 1, doses were escalated from 100 mg BID using a Bayesian optimal interval design. Select doses were to be expanded in Part 2. Primary endpoints are INCB099318 safety, tolerability, and determination of pharmacologically active/maximum tolerated dose (MTD). Secondary and exploratory endpoints include pharmacokinetics, objective response rate per RECIST v1.1, and biomarkers of pharmacologic activity.Table 134P:SafetyTEAEs, n (%)Total patients (N=101)Any gradeGrade ≥3All cause TEAEs94 (93.1)41 (40.6)Occurring in >10% of patientsFatigue33 (32.7)4 (4.0)Constipation24 (23.8)0Nausea23 (22.8)2 (2.0)Anemia17 (16.8)9 (8.9)Decreased appetite15 (14.9)2 (2.0)Diarrhea15 (14.9)2 (2.0)Cough13 (12.9)0Dyspnea13 (12.9)1 (1.0)Vomiting12 (11.9)1 (1.0)Alanine aminotransferase increased11 (10.9)2 (2.0)Immune-related TEAEs11 (10.9)4 (4.0)Serious TEAEs25 (24.8)Occurring in >1 patientAnemia2 (2.0)Cerebrovascular accident2 (2.0)Grade ≥3 Treatment-related TEAEs11 (10.9)Occurring in >1 patientFatigue3 (3.0)Anemia2 (2.0) Open table in a new tab As of June 23, 2023, 101 patients had received INCB099318 at doses from 100 to 800 mg QD or BID (Part 1, n=64; Part 2, n=37). Median age was 58 years (range, 29-89), 59.4% were women, 86.1% were White, 68.3% had ≥2 prior lines of treatment, and 9.9% had prior IO. Most common tumor types were cervical (17.8%), ovarian (10.9%), and colorectal (5.9%). No dose-limiting toxicities were observed and MTD was not reached. In Part 2, 3 dose levels were expanded (400 mg BID, n=18; 800 mg BID n=14, 800 mg QD, n=5). Overall, 82 patients (81.2%) discontinued treatment, 69 (68.3%) due to disease progression. 94 (93.1%) patients had treatment-emergent adverse events (TEAEs) (Table). Several responses have been observed, and updated results will be presented. INCB099318 was generally well tolerated at all doses tested. Preliminary safety and response outcomes support future development of INCB099318 for the treatment of select advanced solid tumors.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".