GI Oncology Daily Digest

SOLARIS (Alliance A021703) is the properly powered phase III test of an idea that has circled colorectal oncology for a decade — that high-dose vitamin D3 improves outcomes in metastatic disease. 455 patients with previously untreated mCRC were randomized double-blind across the US National Clinical Trials Network to mFOLFOX6 or FOLFIRI plus bevacizumab with either high-dose D3 (8000 IU daily for 14 days as a loading dose, then 4000 IU daily) or standard-dose D3 (400 IU daily), continued until progression or intolerance. Median PFS was 11.8 months (95% CI 10.3–13.3) with high-dose versus 10.3 months (9.4–12.2) with standard dose — a 1.5-month numerical gap that did not approach significance (1-sided log-rank p=0.25). The secondary endpoints were equally flat: objective response rate 51% (44–58%) versus 44% (37–50%), p=0.12, and median overall survival 25.6 versus 27.0 months, p=0.66. There were no clinically meaningful differences in grade ≥3 adverse events (neutropenia 32% vs 30%, hypertension 20% vs 23%) and no excess vitamin D–associated toxicity. Median follow-up was 20 months; database freeze July 2024.

Familial adenomatous polyposis has almost no medical therapy — patients face lifelong endoscopic surveillance and eventual colectomy, and the duodenum remains a mortality driver long after the colon is gone. This phase II trial assigned 30 FAP patients to three dosing regimens of encapsulated rapamycin (eRapa, 0.5 mg): every other day (cohort 1), daily every other week (cohort 2), or daily (cohort 3), with safety, pharmacokinetics, and 6-month percentage change from baseline in colorectal polyp burden as co-primary endpoints. 29 of 30 patients (97%) completed the 12-month study with predictable bioavailability; low-grade adverse events were frequent and most pronounced on daily dosing, and 2 patients discontinued for toxicity. Cohort 1 had the largest 6-month reductions — duodenal polyp burden −33.3% (IQR 90; p=0.04), colorectal polyp burden −39.4% (IQR 108.9; p=0.28), and total polyp burden −38.6% (IQR 88.5; p=0.26) — so only the duodenal endpoint cleared significance. Pooling the two intermittent cohorts against daily dosing, duodenal burden fell at 6 months (p=0.04) and total burden improved at 12 months (p=0.05). The 0.5 mg daily-every-other-week schedule now advances to phase III.

LOAd703 is an oncolytic adenoviral vector engineered to deliver CD40L and 4-1BBL directly into the tumour microenvironment — an attempt to inflame immunologically cold tumours from the inside rather than through systemic checkpoint blockade. LOKON002 (NCT03225989) was an open-label, single-arm phase I/IIb trial giving up to eight biweekly intratumoral injections plus a gemcitabine-based backbone to 41 patients with pancreatic (n=29), colorectal (n=5), ovarian (n=4), and biliary (n=3) cancers, with dose escalation by standard 3+3 and expansion of the two highest dose levels. Tolerability was the primary endpoint and was met: the commonest treatment-related events were pyrexia (76%), chills (39%), and fatigue (34%), predominantly grade 1–2. Response was both dose- and setting-dependent — ORR was 0 in the 5×10^10 viral particle cohort, 25% at 1×10^11, and 12% at 5×10^11 — and every patient with an objective response had first-line pancreatic cancer, giving a 35% ORR within that subgroup. Paired tumour sampling showed significant upregulation of Th1 immunity biomarkers at week 13, with several patients achieving long-term stable disease.