# Retinoblastoma Phase II Expanded Access Clinical Trial

> **NIH FDA R01** · TARGETED THERAPY TECHNOLOGIES, LLC · 2024 · $650,000

## Abstract

Abstract
Retinoblastoma (RB) is a micro-orphan disease intraocular cancer in infants and children (typically diagnosed
between birth and 5 years of age). Approximately 250 new cases are diagnosed annually in the United States.
Standard of care for retinoblastoma includes removing the affected eye (safest) or attempted salvage of the eye
starting with systemic or intra-arterial chemotherapy. Since external beam radiotherapy incurs life-long high risk of
second cancers in RB H1 patients carrying the RB1 cancer predisposition gene, it is reserved for last effort to save
a last eye. There is no FDA approved intervention for retinoblastoma. Topotecan Chemoplaque (IND #112785) as
a single (one) treatment achieves sustained local six-week delivery of Topotecan directly to the interior of the eye
while sequestering Topotecan from washout to peripheral circulation. The RP2D was determined to be 2 doses: 0.9
mg (single Chemoplaque) or 1.2 mg (two 0.6 mg Chemoplaques), depending on patient age and tumor features.
Sustained CR (absence of Standard of Care therapies after the Chemoplaque) was achieved in 10/12, 0.9 mg,
83% and 8/9, 1.2 mg, 89% evaluable for efficacy.
In the 1.2 mg dose that we plan to progress in the proposed trial, the sustained CR rate is 89%. All the CRs are
out > 2 years. All the CRs were in refractory settings, including refractory solid tumor, refractory vitreous seeds,
and refractory subretinal seeds. At the RP2D based on swimmer plot analysis, for patients that were refractory to
IAC, treatments before and after Chemoplaque are as follows:
As such, the Chemoplaque significantly reduces subsequent treatment burden in patients refractory to IAC.
Toxicity analysis includes 22 participants treated at the RPD2 (12, 0.9 mg /10, 1.2 mg).
No systemic toxicity was observed. At all time points, plasma Topotecan levels were below limits of detection
except one trace (<1 ng/ml detection only on day 1 in the smallest child). Vitritis/scleritis developed in 2
participants after 4 weeks (1/12 at 0.9 dose, and 1/10 at 1.2 dose), which responded to local steroids with resulting
sustained CRs (now out > 2 years). All eyes have a full thickness chorio-retinal scar directly opposite the
Chemoplaque. All participants reported signs of inflammation and reduced well-being, similar to babies teething
that resolves in all cases following Chemoplaque removal and (if applied) is responsive to local steroids. The
Phase I Trial RP2D analysis suggests that Topotecan Chemoplaque has good, sustained effectiveness in refractory
settings including refractory solid tumor, refractory vitreous and subretinal seeds—given as a single application
(one treatment) without need for repeat treatment or multiple cycles. To our knowledge, there are no
retinoblastoma interventions that are effective (result in CRs) after a single application, and further, there are none
that are effective across all lesion types let alone as a single application. The chemoplaque has demonstrated
r...

## Key facts

- **NIH application ID:** 11105727
- **Project number:** 1R01FD008443-01
- **Recipient organization:** TARGETED THERAPY TECHNOLOGIES, LLC
- **Principal Investigator:** Ricardo A Carvalho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2024
- **Award amount:** $650,000
- **Award type:** 1
- **Project period:** 2024-09-15 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11105727

## Citation

> US National Institutes of Health, RePORTER application 11105727, Retinoblastoma Phase II Expanded Access Clinical Trial (1R01FD008443-01). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/11105727. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*