2026-05-31

digest generated 2026-07-19

RASolute 302: mOS 13.2 vs 6.7mo (HR 0.40), daraxonrasib roughly doubles OS in previously-treated metastatic pancreatic ca.

TL;DR

GI posted the day's biggest number (RASolute 302 roughly doubling 2L pancreatic OS), but the RT slate is the reader's story: in prostate, adding enza (ENZARAD) or protons (COMPPARE) to the RT+ADT backbone failed while intraprostatic CAN-2409 improved DFS (HR 0.70); thoracic OCEANUS found sequential iRT beat concurrent (HR 0.68, real-world).

Prostate

RT-intensification theme dominates: adding enza (ENZARAD) or protons (COMPPARE) to the RT+ADT backbone failed, while intraprostatic CAN-2409 hit its DFS endpoint.

Early signal

COMPPARE

ForDe novo localized prostate cancer, excl very-high-risk and metastatic

TL;DRProton vs IMRT: no difference in bowel urgency (6% vs 5.7%), ≥G2 GI tox, or 3-yr biochemical control in localized prostate.

Why it mattersRadiation oncology

The RT read is that rectal spacer use, not proton vs photon, moved GI toxicity: 2-yr G2+ fell to ~4.4-4.7% with a spacer vs 7.2-8.7% without (p=0.009), similar across modalities. Protons showed no toxicity or 3-yr biochemical-control edge, arguing against the proton premium for localized disease.

COMPPARE — Endpoint IMRT Proton P

Bowel urgency (EPIC) 6% 5.7% 0.28
Bowel frequency (EPIC) 4% 3.5% 0.43
GI tox ≥G2 (CTCAE) 5.6% 5.2% 0.60
3-yr FFDP (PSA) 97.9% 98.0% 0.90

Endpoint	IMRT	Proton	P
Bowel urgency (EPIC)	6%	5.7%	0.28
Bowel frequency (EPIC)	4%	3.5%	0.43
GI tox ≥G2 (CTCAE)	5.6%	5.2%	0.60
3-yr FFDP (PSA)	97.9%	98.0%	0.90

+1 more figure

Group	2-yr G2+ GI toxicity (95% CI)
IMRT, no spacer	7.2% (5.0%, 9.9%)
Proton, no spacer	8.7% (5.0%, 14%)
IMRT, spacer	4.4% (2.8%, 6.4%)
Proton, spacer	4.7% (3.6%, 6.0%)

6 details 5 trials watching

Design

Prospective comparative effectiveness study (COMPPARE, PCORI-funded), non-randomized proton vs photon cohorts across 51 centers. 2524 accrued July 2018-October 2022. Early results, short follow-up.

Population & inclusion

De novo localized prostate cancer, excluding very-high-risk and metastatic. Proton cohort n=1500, photon (IMRT) cohort n=1000.

Radiotherapy

Proton therapy vs IMRT; rectal spacer use captured as a covariate (FDA-approved 2015). Dose/fractionation and target volume not reported in source.

Endpoints

Co-primary patient-reported bowel urgency and frequency (EPIC) and ≥G2 GI toxicity (CTCAE v5), each powered 90%. Exploratory: 3-yr freedom from PSA progression.

Results

No significant proton advantage on any endpoint (all p ≥ 0.28). Observed toxicity fell far below design assumptions (hypothesized IMRT GI tox 29%, actual 5.6%).

Safety

Rectal spacer reduced 2-yr cumulative G2+ GI toxicity in both arms (p=0.009); the spacer effect exceeded any proton-vs-IMRT difference.

vs leading data

Directionally consistent with PARTIQoL (randomized proton vs IMRT, localized prostate), which found no bowel-QoL advantage for protons.

Applies to

de novo localized prostate cancer treated with definitive protons or IMRT

Does not represent very-high-risk or metastatic disease.

Limitations

Non-randomized cohorts (selection bias, residual confounding); short follow-up leaves late GU/GI toxicity and long-term control unanswered; dose/fractionation not reported.

Rationale

Prospective but non-randomized cohorts (selection bias); early results, short f/u leave late toxicity and long-term control open. Null aligns with randomized PARTIQoL non-superiority.

Monday clinic

In localized prostate cancer (de novo, excluding very-high-risk and metastatic), these early data question routine proton use over IMRT for GI toxicity or 3-yr control; they do not yet speak to late toxicity or long-term outcomes.

Open questions

Late GU/GI toxicity beyond 3 years

active Proton Therapy vs. IMRT for Low or Intermediate Risk Prostate Cancer Phase NA

n=454 · primary completion 2025-12 · proton vs IMRT, side-effect head-to-head

active A Prospective Comparative Study of Outcomes With Proton and Photon Radiation in Prostate Cancer Phase NA

n=3000 · primary completion 2026-02 · 3000-pt proton vs IMRT QOL + toxicity cohort

recruiting Protons Vs. Photons for High-risk Prostate Cancer Phase NA

n=400 · primary completion 2027-03 · proton vs photon, primary late GI toxicity
Long-term biochemical and metastasis-free control with protons vs IMRT

active A Prospective Comparative Study of Outcomes With Proton and Photon Radiation in Prostate Cancer Phase NA

n=3000 · primary completion 2026-02 · proton vs IMRT cohorts, disease-control endpoint

active Mild Hypofractionation With Proton Therapy or IMRT for Intermediate-Risk Prostate Cancer

n=303 · primary completion 2026-12 · proton vs IMRT hypofx, improve cancer control

Sourced from @QianJanieQin

📚 Sources · 🐦 1 tweet

#COMPPARE early results: in localized #ProstateCancer, #proton therapy vs #IMRT showed no sig difference in pt-reported bowel urgency/frequency, ≥G2 GI toxicity, or 3-year biochemical control. Longer follow-up needed for late toxicity/long term outcomes #ASCO2026 pic.twitter.com/yli4l8nEOY
— QianJanieQin (@QianJanieQin) May 31, 2026

Radiation Curative Real-world evidence Early signal

Caveats dominate

PROTEUS

TL;DRMost distant mets PSMA PET-detected (53.0% APA vs 60.7% control); preview NEJM data, MFS benefit's clinical meaning contested.

6 details 1 trial watching

Design

Randomized, apalutamide + ADT vs ADT alone. Results just posted (NEJM online); full ASCO26 presentation pending, so this is a preview read.

Results

Most distant metastases were PSMA PET-detected: 53.0% in the apalutamide group vs 60.7% in the control group. Primary MFS effect size not reported in source.

Limitations

MFS events were predominantly PET-detected, raising lead-time / detection-bias concerns about the endpoint. The 50-vs-60 BCR/100 figures circulating are an illustrative hypothetical, not PROTEUS primary data.

Discussion

Curator frames it as 'homerun vs largest negative' pending full data. A companion thought experiment argues PSMA PET vs conventional detection differences could account for much of the apparent metastasis delta.

Rationale

Preview NEJM data; primary effect size not in source. Most MFS events PSMA PET-detected (53.0% vs 60.7%), raising lead-time/detection bias that undermines the MFS read.

Open questions

Does the MFS benefit hold on OS or conventional-imaging endpoints?

active An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS Phase 3

n=1503 · primary completion 2026-06 · apalutamide MFS by conventional imaging (BICR)
How much of the MFS delta reflects PSMA PET lead-time bias?

Sourced from @DrSpratticus, @seanmmcbride

📚 Sources · 🐦 3 tweets

#ASCO26
The PROTEUS trial results are now online...buckle up as we wait to see the full presentation. This is going to be a trial that is likely highly controversial until the full results are published.

Some may call this a homerun, others may call this the largest negative…
— Daniel E Spratt (@DrSpratticus) May 31, 2026

📝 Note until the trial is released later this is preview

Thought experiment:

Let's take a very simple hypothetical trial involving 100 patients in the APA arm and 100 patients in the ADT alone arm. Pulling from PROTEUS EFS data, assume that, by 5 years, 60 patients in the ADT arm have had a BCR compared to 50 in the ADT+APA arm.… pic.twitter.com/WJaiDlJnQs
— Sean McBride (@seanmmcbride) May 31, 2026

📝 note add commentary to proteus discussion

#ASCO26
Talk about real-time updates. NEJM paper now online and my predictions and inferences appear true.

Majority of MFS events were by PET not conventional imaging. "Most distant metastases were identified by PSMA PET (53.0% of those in the apalutamide group and 60.7% in the… https://t.co/Yz4myY0flq
— Daniel E Spratt (@DrSpratticus) May 31, 2026

📝 add to proteus data

Systemic Curative Phase 3 RCT Caveats dominate

Confirmatory

CAN-2409 NCT01436968

ForIntermediate or high-risk localised prostate cancer, EBRT candidates

TL;DRDFS HR 0.70 (0.52-0.94, p=0.016) adding intraprostatic CAN-2409 to EBRT in intermediate/high-risk localised prostate; OS and PCSM immature.

Why it mattersRadiation oncology

The RT read is local control: 2yr biopsy positivity fell 36.4% to 19.6% (p=0.0015), comparable to adding ADT (RTOG 9408) but on standard 78Gy without a brachy or SIB boost. Whether it adds over modern dose-intensification plus ADT is the open integration question, since ADT was optional and no boost was used.

Endpoint CAN-2409 Placebo HR / p

DFS median NR 86.1 mo HR 0.7 (0.52-0.94), p=0.0155
2yr biopsy pCR 80.4% 63.6% n/a
2yr local recurrence 19.6% 36.4% p=0.0015

Endpoint	CAN-2409	Placebo	HR / p
DFS median	NR	86.1 mo	HR 0.7 (0.52-0.94), p=0.0155
2yr biopsy pCR	80.4%	63.6%	n/a
2yr local recurrence	19.6%	36.4%	p=0.0015

+1 more figure

Trial	Intensifier	Local endpoint: control → intensified
RTOG 9408	+4mo ADT	2yr biopsy+ 40% → 20%
ASCENDE-RT	LDR brachy boost	10y local failure 7.1% → 1.5%
FLAME	SIB 95Gy	Crude local failure 7.7% → 2.7%
CAN-2409	+CAN-2409	2yr biopsy+ 36.4% → 19.6%

8 details

Design

Phase 3, double-blind, placebo-controlled RCT, 2:1 randomisation, N=745 across 51 US and Puerto Rico centres. Median follow-up 50.3 mo.

Population & inclusion

Intermediate or high-risk localised prostate cancer, ECOG 0-2, planned for EBRT. Stratified by risk category and ADT use. 79% White, 16% Black.

Radiotherapy

EBRT 78 Gy/2 Gy, or hypofractionated 60 Gy/3 Gy or 70 Gy/2.5 Gy. ADT optional. No dose-escalation or brachytherapy boost mandated.

Regimen

Three intraprostatic aglatimagene injections (5×10^11 viral particles) plus valacyclovir prodrug, versus placebo plus valacyclovir.

Endpoints

Primary: disease-free survival (recurrence or death, ITT). Secondary/exploratory: OS, PCSM, 2-year post-RT biopsy pathologic response.

Results

Primary met: DFS favoured aglatimagene; OS and PCSM immature, not significantly different. Arm-by-endpoint values in the results figure.

Event (G3+)	Aglatimagene	Placebo
Any TEAE	8% (40/479)	7% (17/232)
Acute kidney injury	2% (9/479)	2% (4/232)
Serious AEs	6% (28/479)	7% (17/232)

Safety

Grade 3+ TEAEs 8% vs 7%; most common acute kidney injury (2% both arms). Serious AEs 6% vs 7%. No treatment-related deaths.

vs leading data

Discussant benchmarked the biopsy-positivity gain against ADT (RTOG 9408), brachytherapy boost (ASCENDE-RT), and SIB (FLAME) as established local-control intensifiers.

Applies to

intermediate or high-risk localised prostate cancer treated with definitive EBRT

Does not represent post-prostatectomy, salvage, or metastatic disease.

Limitations

DFS is a composite surrogate; OS and PCSM immature. ADT optional, no boost mandated, confounding added value over modern intensification. Accrual (2012-2021) predates PSMA staging.

Rationale

Positive phase 3 primary (DFS) but on a surrogate/composite; OS and PCSM immature (1 event/arm). Additive benefit over modern dose-intensification plus ADT unproven.

Monday clinic

In intermediate or high-risk localised prostate cancer planned for definitive EBRT, this informs whether an added intraprostatic biologic could improve local control; it does not extend to post-prostatectomy, salvage, or metastatic settings.

Open questions

Does the local-control gain add over modern dose-escalation and ADT?
Do DFS and pCR gains translate to overall or cancer-specific survival?
Optimal ADT and RT-intensification pairing with intraprostatic CAN-2409

Sourced from @MikeSerzanMD, DeWeese, Theodore L et al.

📚 Sources · 🐦 1 tweet · 📄 1 paper

🗣️Prostate Oral Abstract #ASCO25

👉Dr @angela_jia_ discusses "Better Treatments, Better Selection: Improving Patient Outcomes in Localized Prostate Cancer"

🔑 KEY TAKE AWAYS
- #CAN2409 improves DFS and 2yr PathCR however PCSM and OS remain immature.
❓How to integrate with… pic.twitter.com/WamsneYBI1
— Michael Serzan, MD (@MikeSerzanMD) June 3, 2025

📄 PAPER DeWeese, Theodore L; Manzanera, Andrea; Sylvester, John et al. · The Lancet Oncology (2026-06)

Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial

doi

Abstract

Background About 30% of men with localised prostate cancer undergoing radiotherapy with curative intent have disease recurrence associated with progression-related symptoms and substantial toxicity of salvage therapies. Previous studies with aglatimagene besadenovec (CAN-2409, hereafter referred to as aglatimagene) showed synergy with radiation and immune-mediated cytotoxicity in patients with prostate cancer. We aimed to assess whether addition of aglatimagene plus prodrug (valacyclovir) to standard-of-care external beam radiation therapy (EBRT) could improve disease-free survival in this population. Methods We conducted a phase 3, randomised, double-blind, placebo-controlled trial at 51 medical centres (26 community and 25 institutional or military) across the USA and Puerto Rico in patients with intermediate or high-risk prostate cancer. Patients aged at least 18 years who were planning to undergo EBRT and with an Eastern Cooperative Oncology Group score of 0-2 were eligible. Patients were randomly assigned (2:1) via central block-randomisation to receive either three courses of intraprostatic aglatimagene (5 × 10 11 viral particles) plus valacyclovir or placebo plus valacyclovir, with randomisation stratified by risk category and androgen deprivation therapy (ADT) use. Patients received standard-of-care EBRT (78 Gy in 2 Gy fractions) or hypofractionated EBRT (60 Gy in 3 Gy fractions or 70 Gy in 2·5 Gy fractions) with optional ADT. The primary endpoint was disease-free survival, defined as time-from-randomisation to prostate cancer recurrence or death in the intent-to-treat population (all randomly assigned patients). Safety was assessed in all individuals who received at least one injection. The trial is registered at ClinicalTrials.gov, NCT01436968, and long-term follow-up is ongoing. Findings Between Feb 21, 2012, and Sept 9, 2021, 745 men (591 [79%] White, 121 [16%] Black) were randomly assigned to receive aglatimagene plus valacyclovir (n=496) or placebo plus valacyclovir (n=249). After a median follow-up of 50·3 months (IQR 35·2-63·3), median disease-free survival was not reached (95% CI 121·78 to not reached) in the aglatimagene plus valacyclovir group versus 86·1 (IQR 29·7-143·0) months in the placebo plus valacyclovir group (hazard ratio 0·70, 95% CI 0·52-0·94; p=0·016). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 40 (8%) of 479 patients in the aglatimagene group and 17 (7%)of 232 patients in the placebo group. The most common TEAE of grade 3 or worse was acute kidney injury in both the aglatimagene group (nine [2%] of 479 patients) and the placebo group (four [2%] of 232 patients). Serious adverse events occurred in 28 (6%) of 479 patients in the aglatimagene group and 17 (7%) of 232 in the placebo group. Treatment-related serious adverse events occurred in eight (2%) patients in the aglatimagene group (four acute kidney injury, two pyrexia, and one each influenza-like symptoms and urinary retention) and five (2%) in the placebo group (four acute kidney injury, and one each increased creatinine levels and skin rash; one patient reported two serious adverse events). No treatment-related deaths were reported. Interpretation Aglatimagene plus valacyclovir was associated with longer disease-free survival than placebo plus valacyclovir when added to standard of radiotherapy for the treatment of localised prostate cancer, offering a meaningful benefit without increasing clinically significant toxicity. Funding Candel Therapeutics and US National Institutes of Health.

📝 https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(26)00071-9/fulltext

Combined Curative Phase 3 RCT Confirmatory

GI Upper

First targeted 2L option to roughly double OS over chemo in metastatic pancreatic; no RT relevance.

Practice-changing

RASolute 302

ForPreviously treated metastatic pancreatic cancer (RAS-mut or WT)

Overall survival

HR 0.40

95% CI 0.30-0.53, P<0.001; mOS 13.2 vs 6.7 mo (overall pop)

TL;DRmOS 13.2 vs 6.7mo, HR 0.40 (0.30-0.53), P<0.001 for daraxonrasib vs investigator's-choice chemo in previously treated metastatic pancreatic cancer.

Monday clinic

In previously treated metastatic pancreatic cancer with a RAS mutation, daraxonrasib's OS benefit supports it as a systemic option over chemotherapy; the signal does not extend to treatment-naive or localized disease.

RASolute 302 — Population · Arm Median OS HR (death) 12-mo OS

G12 · Daraxonrasib 13.2 mo (10.0-NR) 0.40 (0.30-0.54) 53.3%
G12 · Chemo 6.6 mo (5.4-8.2) — 8.7%
Overall · Daraxonrasib 13.2 mo (10.0-NR) 0.40 (0.30-0.53) 53.2%
Overall · Chemo 6.7 mo (5.8-8.0) — 17.3%

Population · Arm	Median OS	HR (death)	12-mo OS
G12 · Daraxonrasib	13.2 mo (10.0-NR)	0.40 (0.30-0.54)	53.3%
G12 · Chemo	6.6 mo (5.4-8.2)	—	8.7%
Overall · Daraxonrasib	13.2 mo (10.0-NR)	0.40 (0.30-0.53)	53.2%
Overall · Chemo	6.7 mo (5.8-8.0)	—	17.3%

7 details 1 trial watching

Design

Phase 3 RCT, daraxonrasib vs investigator's-choice chemotherapy in previously treated metastatic pancreatic cancer. Two prespecified populations: RAS G12-mutant and overall (G12/G13/Q61 or no RAS mutation identified).

Population & inclusion

Previously treated metastatic pancreatic cancer. RAS G12 arm n=228 vs 231; overall n=248 vs 252. Overall population also includes tumors with no identified RAS mutation.

Regimen

Daraxonrasib, an oral RAS(ON) multi-selective inhibitor targeting active GTP-bound RAS, vs investigator's choice cytotoxic chemotherapy.

Results

Primary OS met: median 13.2 vs 6.7 mo, HR 0.40 (0.30-0.53), P<0.001 (overall); HR 0.40 (0.30-0.54) in RAS G12. 12-mo OS 53% vs 17% (overall). Deaths 32% vs 55-56%.

Applies to

previously treated metastatic pancreatic cancer with RAS mutations (G12/G13/Q61) or no identified RAS mutation

Does not represent treatment-naive or localized/resectable pancreatic cancer.

vs leading data

Chemo control (6.6-6.7 mo) matches the historic 2L metastatic PDAC benchmark; no prior targeted agent has shown an OS signal of this magnitude in this setting.

Limitations

Data limited to a single ASCO LBA OS figure; full safety and PFS not yet reported. Open-label; daraxonrasib median OS upper CI not reached (10.0-NR), so tail durability is immature.

Rationale

Randomized phase 3, OS primary hit HR 0.40 in 2L metastatic PDAC where no targeted SOC exists; hard endpoint, unprecedented magnitude. Full LBA data pending.

Open questions

Sequencing and combination with 1L chemotherapy

recruiting Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma Phase 3

n=900 · primary completion 2028-06 · 1L daraxonrasib + gem/nab-paclitaxel combination
Efficacy across RAS-WT vs RAS-mutant subsets
Full safety and toxicity profile

Sourced from @GIMedOnc

📚 Sources · 🐦 1 tweet

#ASCO26

This one is special.

This is the hottest paper of 2026 and potentially in the history of pancreatic cancer.

Let’s dive in.

RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer
Abstract LBA5 (soon!)… pic.twitter.com/Lq7PEjOWAo
— Nicholas Hornstein (@GIMedOnc) May 31, 2026

Systemic Palliative Phase 3 RCT Practice-changing

GI Lower

RT delivered first as an immune primer in MSS metastatic rectal; provocative conversion signal but single-arm, responses not yet durable.

Early signal

MIRACLE-2

For1L unresectable MSS rectal cancer, synchronous liver/lung mets

TL;DR68% ORR, mOS 23.2mo, 18% NED with RT-primed chemo + tislelizumab in MSS unresectable met rectal ca.

Why it mattersRadiation oncology

The RT-relevant read is technique: HFRT to the primary plus HFRT/SBRT to mets, delivered first to prime immunity, but no dose or fractionation in source, so it doesn't transfer to practice yet. 18% (9/50) converted to NED via resection or watch-and-wait. Near-universal lymphopenia (95.9% all-grade, 36.7% G3/4) undercuts a strategy premised on RT-driven T-cell activation.

MIRACLE-2 — Metric n (%) 95% CI

CR 1 (2.0%)
PR 33 (66.0%)
SD 10 (20.0%)
PD 6 (12.0%)
ORR 34 (68.0%) 53.6-80.0%
DCR 44 (88.0%) 76.0-95.2%
ETS 38 (76.0%) 62.4-86.8%

Metric	n (%)	95% CI
CR	1 (2.0%)
PR	33 (66.0%)
SD	10 (20.0%)
PD	6 (12.0%)
ORR	34 (68.0%)	53.6-80.0%
DCR	44 (88.0%)	76.0-95.2%
ETS	38 (76.0%)	62.4-86.8%

9 details 2 trials watching

Design

Prospective single-arm phase I, N=50, Fudan University Shanghai Cancer Center. Data cutoff Dec 31 2025; median follow-up 19.9 mo (95% CI 16.4-23.4).

Population & inclusion

MSS rectal cancer, primary ≤10cm from anal verge, synchronous unresectable mets. 76% male, median age 57; 52% liver, 8% lung, 40% both; RAS/BRAF-mut 56%.

Radiotherapy

RT delivered first as an immune primer: HFRT to the primary, HFRT or SBRT to metastases. Dose, fractionation, and target volumes not reported in source.

Regimen

Post-RT, biomarker-gated: FOLFOX-bevacizumab-tislelizumab (RAS/BRAF-mut) or FOLFIRI-cetuximab-tislelizumab (WT); tislelizumab 200mg Q2W. Resection/metastasectomy if converted, watch-and-wait if primary cCR.

Endpoints

Primary: ETS rate (≥20% target shrinkage at 8wk). Secondary: DCR, DOR, OS, PFS, safety.

Results

ETS 76.0%, ORR 68.0%, DCR 88.0%; 18% (9/50) reached NED. Median OS 23.2mo, PFS 9.3mo, DOR 8.0mo (endpoints in table).

Endpoint	Median	95% CI	1-yr rate
OS	23.2 mo	15.1-31.3	93.3%
PFS	9.3 mo	7.1-11.5	33.4%
DOR (n=34)	8.0 mo	5.2-10.8	20%

Applies to

treatment-naive MSS rectal cancer with synchronous unresectable liver/lung metastases

Does not represent MSI-H tumors, resectable disease, or non-rectal colorectal primaries.

Limitations

Single-arm phase I, N=50, no comparator to isolate RT's contribution. Surrogate primary (ETS at 8wk), short median DOR (8mo), and near-universal lymphopenia (95.9%).

Rationale

Single-arm phase I, N=50; surrogate primary (ETS at 8wk); no comparator to isolate RT's contribution to the immune-priming effect.

Open questions

RT's added benefit over chemo plus PD1 alone in MSS mCRC
Optimal RT dose and fractionation for immune priming in MSS mCRC

recruiting Regorafenib Alone or in Combination With Hypofractionated/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer Phase 2

n=108 · primary completion 2025-04 · randomized hypofrac+LDRT + toripalimab, MSS mCRC

recruiting Standard Systemic Therapy Combined With High/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer Phase 2

n=96 · primary completion 2026-12 · high + low-dose RT + toripalimab in MSS mCRC
Predictive biomarker for MSS response to trimodal therapy

Sourced from @NiuSanford

📚 Sources · 🐦 1 tweet

MIRACLE-2: RT to primary/mets -> chemo + tislelizumab in MSS unresectable met rectal ca (N=50): 68% ORR & median OS 23 mo.

Early, single-arm data, but ~1 in 5 pts reached NED.

Suggests RT + systemic + PD1 blockade could overcome immune resistance in MSS mCRC. #ASCO26 @OncoAlert pic.twitter.com/sjnUW8x7f3
— Dr. Nina Niu Sanford (@NiuSanford) May 31, 2026

Combined Curative Phase 1 Early signal

Thoracic / Lung

Real-world only: sequencing RT before ICI beat concurrent iRT for OS, but hypothesis-generating with no RT technique reported.

Caveats dominate

OCEANUS

ForAdvanced/refractory NSCLC on immunoradiotherapy, median age 64, 74% male

TL;DRSequential iRT beat concurrent for real-world OS in newly-dx advanced NSCLC: median 20.3 vs 16.0 mo, HR 0.68 (0.47-0.99), P=.045.

Why it mattersRadiation oncology

Sequential iRT (ICI and RT not overlapping) beat concurrent for real-world OS in newly-dx advanced NSCLC, HR 0.68 (0.47-0.99), P=.045, favoring temporal separation of RT from ICI. RT dose, fractionation, and target volume aren't in the source, so the signal can't yet transfer to a specific plan. The refractory RT+ICI-maintenance read was NS (P=.20).

7 details 1 trial watching

Design

Territory-wide real-world cohort (OCEANUS, Hong Kong CDARS, >90% population coverage); NSCLC diagnosed 2010-2021 who received iRT. Overlap-weighting propensity score primary, IPTW sensitivity; landmark-based OS with weighted Kaplan-Meier and Cox (restricted mean survival time where PH violated).

Population & inclusion

335 of 3522 ICI-treated pts received RT: 155 newly-dx advanced, 180 refractory. Median age 64 (34-90), 73.7% male. Refractory analysis required survival ≥90 days (landmark).

Radiotherapy

RT dose, fractionation, modality, and target volume not reported in source. The variable studied is timing of RT relative to ICI (sequential vs concurrent), not technique.

Results

Both comparisons favored the sequential / ICI-maintenance arm (magnitudes in table). Chemotherapy was associated with longer OS in newly-dx pts only; not significant in refractory disease.

Setting / comparison	Experimental OS	Control OS	HR / P value
Newly-dx advanced, sequential vs concurrent iRT	20.3 mo (95% CI 13.3-NR)	16.0 mo (95% CI 8.3-30.0)	HR 0.68 (0.47-0.99), P=.045
Refractory, RT + ICI maintenance vs RT alone	11.2 mo (95% CI 7.9-20.6)	6.7 mo (95% CI 4.4-17.4)	P=.20 (ns)

vs leading data

Randomized data on iRT sequencing in advanced NSCLC are limited (stated by authors). RT-before-ICI direction is consistent with the PACIFIC consolidation paradigm, but PACIFIC treated curative-intent unresectable stage III with concurrent chemoRT, a different population.

Applies to

advanced or refractory NSCLC receiving immunoradiotherapy, predominantly male, median age 64

Does not represent curative-intent stage III chemoRT, oligometastatic, or ICI-treated patients who did not receive RT.

Limitations

Observational: sequential vs concurrent not randomized, residual confounding by indication despite weighting. Small subgroups (155 newly-dx). Refractory comparison non-significant (P=.20).

Rationale

Observational real-world cohort; sequential-vs-concurrent not randomized, confounding by indication despite propensity weighting. Small subgroups (155 newly-dx). Authors label it hypothesis-generating.

Monday clinic

In newly-diagnosed advanced NSCLC starting immunoradiotherapy, this real-world signal supports separating RT from ICI in time rather than delivering them concurrently; it does not extend to refractory disease, where the RT-plus-ICI-maintenance benefit was not significant.

Open questions

Optimal RT-ICI sequencing (sequential vs concurrent) in advanced NSCLC

active PD-1 Inhibitor and Chemotherapy With Concurrent Irradiation at Varied Tumour Sites in Advanced Non-small Cell Lung Cancer Phase 3

n=327 · primary completion 2026-12 · phase 3 concurrent RT+PD-1 in stage IIIB/IV NSCLC
Value of ICI maintenance after RT in refractory NSCLC

Sourced from Zhou et al.

📚 Sources · 📄 1 paper

📄 PAPER Zhou; Wang; Lee et al. · JAMA oncology (2026-05)

Combination of Radiotherapy and Immunotherapy in Advanced Non-Small Cell Lung Cancer.

PMID 41885834 → doi full text (PMC)

Abstract

IMPORTANCE: The optimal sequencing of radiotherapy (RT) combined with immunotherapy (iRT) and the value of chemotherapy remain undefined for advanced non-small cell lung cancer (NSCLC), where randomized data are limited. OBJECTIVE: To compare real-world overall survival (OS) between sequential and concurrent iRT in newly diagnosed advanced NSCLC, assess the effect of immune checkpoint inhibitor (ICI) maintenance after RT in refractory disease, and evaluate the association of chemotherapy with survival. DESIGN, SETTING, AND PARTICIPANTS: This is a territory-wide study (OCEANUS) based on the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System (more than 90% population coverage). Patients with NSCLC diagnosed from January 1, 2010, to December 31, 2021, who subsequently received iRT for advanced or refractory disease were included. Overlap weighting was the primary propensity score-weighted method, with inverse probability of treatment weighting used for sensitivity analysis. Data were analyzed from December 2024 to April 2025. EXPOSURES: Sequential vs concurrent iRT for newly diagnosed advanced NSCLC; RT with vs without ICI maintenance for refractory NSCLC; receipt of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary outcome was real-world OS after landmark, estimated with weighted Kaplan-Meier and Cox models. When proportional hazards were violated (per Schoenfeld residuals), treatment effects were summarized using restricted mean survival time. RESULTS: Of 3522 patients who received ICIs, 335 received RT, including 155 with newly diagnosed advanced and 180 with refractory NSCLC. Of these, 247 (73.7%) were male, and the median (range) age was 64 (34-90) years. In newly diagnosed NSCLC, patients treated with sequential iRT had significant longer real-world OS than those treated with concurrent iRT (median, 20.3 months [95% CI, 13.3 to not reached] vs 16.0 months [95% CI, 8.3-30.0]; adjusted hazard ratio, 0.68; 95% CI, 0.47-0.99; P = .045). Chemotherapy was also associated with longer survival in patients with newly diagnosed advanced NSCLC. In refractory NSCLC, RT with ICI maintenance was associated with a numerically longer median real-world OS (11.2 months [95% CI, 7.9-20.6] vs 6.7 months [95% CI, 4.4-17.4]; P = .20). Addition of chemotherapy was not significant for real-world OS. Inverse probability of treatment weighting analyses produced similar estimates. CONCLUSIONS AND RELEVANCE: In this cohort study, sequential iRT was associated with longer survival than concurrent iRT in patients with newly diagnosed advanced NSCLC, and chemotherapy was associated with longer survival. In patients with refractory NSCLC who survived at least 90 days, RT with ICI maintenance resulted in nonsignificantly longer survival and an unclear association with chemotherapy. These findings are hypothesis generating and support prospective randomized studies to define optimal sequencing of iRT and use of systemic treatment partners.

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Combined Palliative Real-world evidence Caveats dominate

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6 of 7 study clusters analyzed successfully.

1 cluster dropped

ENZARAD (enzarad)
suppressed via override

🌰 Prostate

COMPPARE

PROTEUS

CAN-2409 NCT01436968

🍽️ GI Upper

RASolute 302

🌀 GI Lower

MIRACLE-2

🫁 Thoracic / Lung

OCEANUS

Prostate

GI Upper

GI Lower

Thoracic / Lung