A phase 1/2 study of intratumoral INT230-6 alone (IT-01) or in combination with pembrolizumab [KEYNOTE-A10] in adult subjects with locally advanced, unresectable and metastatic solid tumors refractory to therapy.
Bibliographic record
Abstract
2592 Background: Study IT-01 (KEYNOTE-A10) evaluates INT230-6, a novel formulation of cisplatin (CIS) and vinblastine (VIN) with an amphiphilic cell penetration enhancer designed for intratumoral (IT) administration, alone or in combination with pembrolizumab (PEM), an antibody to PD-1. INT230-6 dosing is set by a tumor’s volume. In preclinical studies, INT230-6 increases drug dispersion throughout the tumor, allows drug diffusion into cancer cells and recruits dendritic, CD4 and CD8 T cells. The addition of PEM has been shown to improve these responses in models. Phase 1 data indicated INT230-6 alone induced tumor regression in both injected and non-injected lesions. Considering the large volume of drug injected and retained in the tumor, coupled with immune infiltration on biopsies, RECIST response methodology may not capture the benefit of INT230-6 treatment. Methods: IT-01 is an open-label phase 1/2 study, currently enrolling adult subjects with solid tumors in phase 2. INT230-6 was administered IT Q2W for 5 doses alone or with PEM 200mg Q3W. The study seeks to assess the safety and efficacy of IT INT230-6 alone and in combination with PEM. Results: 67 subjects have been enrolled (58 mono and 12 INT230-6 + PEM (3 started in mono, then received combo)) having a median of 3 prior therapies (0, 10). Median age was 60 (42, 85). 20+ cancer types were accrued; breast cancer and sarcoma were the most frequent. Over 500 image guided INT230-6 IT injections were given (253 to deep tumors) at doses of 0.3 to 172mL (86 mg CIS, 17.2 mg VIN) in a single session, which are higher amounts than typical IV doses. PK shows that 95% of INT230-6 active agents remain in the tumor. The most common (> 20%) related TEAEs for INT230-6 alone were localized pain (57%), nausea (36%), fatigue (29%) and vomiting (24%); with grade 3 TEAEs (> 1) of localized pain (5%) and anemia (3%). The safety in the combination was similar. There were no related grade 4 or 5 TEAEs. In evaluable monotherapy subjects (n = 43), the disease control rate (DCR) was 65% vs. 100% in PEM subjects (n = 5). Given the range of dose and entering tumor burden, an exploratory analysis of dose relative to tumor burden (TB) showed that subjects receiving a dose of INT230-6 < 50% of their reported TB (n = 30) had a mOS of 3.5 months. While in subjects receiving a dose of INT230-6 to ≥50% of TB (n = 37), mOS has not yet been reached after a median follow up of 9.5 months (HR: 0.26 (0.13,0.51)). Conclusions: INT230-6 is well tolerated when administered IT as monotherapy and combined with PEM. Given the challenge in assessing overall response rate following IT delivery, an exploratory analysis suggests prolonged survival for subjects receiving an INT230-6 dose ≥50% of their tumor burden compares favorably to the < 50% group and to literature accounting for prognostic factors (ECOG, LDH, # of metastatic sites). Clinical trial information: 03058289.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".