ASCO Abstract

[mistergern]

IMproveMF update: Phase 1/1B trial of imetelstat (IME)+ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1, INT-2, or high-risk (HR) myelofibrosis (MF).
Background:
IME, a first-in-class, direct, and competitive inhibitor of telomerase activity, showed potential survival improvements and disease-modifying activity in the phase 2 IMbark MF trial (NCT02426086). Preclinical evidence demonstrated IME+RUX reduced disease burden better than either agent alone. IMproveMF (NCT05371964) aims to evaluate IME+RUX in pts with INT-1/INT-2/HR MF.
Methods:
IMproveMF is an open-label, single-arm, phase 1/1b trial (part 1: dose escalation; part 2: dose confirmation and expansion) of IME+RUX in adults with DIPSS INT-1, INT-2, or HR MF. In part 1 (up to 21 pts), RUX was required for ≥12 wk with a stable dose for ≥4 wk immediately before adding IME; pts received IME via intravenous infusion at each dose level cohort (4.7, 6.0, 7.5, and 9.4 mg/kg IME sodium; equivalent to 4.4, 5.6, 7.1, and 8.9 mg/kg active dose, respectively) every 28 d based on Bayesian Optimal Interval design to identify the recommended part 2 dose (RP2D). Pts in part 1 were dose adjusted to the RP2D as needed in part 2, with 2 dose reductions allowed. Part 2 of the trial will enroll pts who are RUX naive. Primary endpoints are adverse events (AE), including dose-limiting toxicity (DLT), in part 1 and AEs and 24-wk response rate (≥50% reduction in MF total symptom score [TSS]) in part 2. Secondary endpoints include pharmacokinetics (PK) and clinical activity. Total planned enrollment is ≈41 pts.
Results:
As of 11/04/2024, 17 pts were enrolled in part 1 with a median age of 67 y (71% aged ≥65 y); 7 had INT-1, 9 INT-2, and 1 HR MF. Respective to the dose levels in the Methods, 3, 3, 4, and 7 pts received the corresponding IME dose level. No DLTs were reported for IME; 2 pts had dose reductions due to neutropenia. Five pts discontinued IME (none due to AEs). Four pts had RUX dose reductions (due to AEs and other, n=2 each). AEs were experienced by 15 pts; 8 experienced grade 3 events of anemia (n=4), neutropenia (n=3), leukopenia (n=2), abdominal pain, fatigue, epistaxis, and pneumonia (n=1 each; the latter 2 and 1 anemia event were considered serious AEs). There were no grade 4/5 AEs. There was an overall reduction in TSS from baseline (median, −5 points in maximum absolute reduction up to wk 24) with IME regardless of dosing, and a trend of dose-dependent spleen volume decrease. A reduction in variant allele frequency of several driver mutations was also observed. Hematologic, PK, and additional mutational data will be included in the presentation, as available.
Conclusions:
In part 1 of IMproveMF, no DLTs were observed and the RP2D dose of 9.4 mg/kg IME was determined. AEs were consistent with those observed in other IME clinical trials, and preliminary efficacy was positive, demonstrating the potential of IME+RUX in this pt population with high unmet needs. Part 2 of this trial is ongoing across the US at 6 sites.

[biopearl123]

Nada.

[rccola335]

https://meetings.asco.org/abstracts-pre ... ons/244233

[rccola335]

https://meetings.asco.org/abstracts-pre ... ons/252436

[rccola335]

https://delta.larvol.com/Products/?Prod ... M%20CDT%22

a lot of stuff going on with Imet - nothing bad but nothing wow either

[biopearl123]

Both MF abstracts do not appear to be updated with recent data and only go back to end of 2024. Seems to be a placeholder with potential for updated data to be presented during actual presentation. For example, IMprove only includes part I data and PIII MF study says expected 35% deaths by early 2026 and updated company information shows that timeline as pushed out so these seems to be the abstracts presented at the last meetings and are not updated for some reason.

[lacour_98]

Why would ASCO accept this abstract if no new data and old news? Seems there is something here - no?

[mck]

ASCO late breaking abstract process.....per their online guidelines. I am hoping the submitted abstracts are placeholders with more to come...

The ASCO late-breaking data policy allows for the submission of late-breaking data only for: Randomized phase II and III trials for which no preliminary data are available at the time of the abstract submission deadline (January 28, 2025) OR Original research studies that highlight novel and high-impact research with practice-changing implications.

The initial abstract must be submitted by the January 28, 2025, deadline as a placeholder (shell) abstract submission. The final, updated late-breaking data should be submitted by March 5, 2025, at 12:00 PM ET (noon)—the late-breaking submission deadline. If an updated abstract with data and analyses is not submitted, ASCO will follow up with the authors directly to determine appropriate next steps.

During submission, the submitter will be required to enter all authors and their disclosures, the Background and Methods sections, provide the primary clinical endpoint for analysis, type of analysis, date of planned analysis, and planned statistical methods.

Phase III clinical research trials for which the final data are not available by the March 5 deadline may be granted an exception to submit later; however, the initial trial information MUST have been submitted by the January 28 deadline. Later submission may have a negative impact on placement in the program.

-mck

[biopearl123]

Yup, thanks mck, sure looks like a couple of late breakers with potential new info. The waiting continues.

[Ryan]

Thanks for posting ; the little (very little) move up in pps clearly had nothing to do with this outdated info. I think the tiny move, and more substantially the huge volume, in the stock may have been related to a monthly revenue chart , which I saw posted on stocktwits via X. The stamp on the chart was Bloomberg financial, which obviously could have been doctored but that’s what it said...

Anyways it showed monthly Revenue from Rytelo, the months from July through March looked accurate and aligned with the quarterly public reporting. but the prominent feature of the chart is that it had a bullet point for April, pegged at $18 Million. If true, that would be excellent progress in sales and portend to $50-60 Million in revenue for the quarter, which I confidently presume would be well received by the financial markets. This chart was posted on stocktwits on Wednesday.

[biopearl123]

Looks like there are differences in the way late breaking abstracts are handled between the two organizations:

yes, the policies differ between eha and asco regarding the release of late-breaking abstract titles:
• eha 2025: titles of late-breaking abstracts are not released on may 14. both titles and full content remain embargoed until june 3, 2025, at 15:30 cest. this means they are entirely confidential until that date .