TRAEs by schedule and grade in >5% of the total study population.

Table S3: Antibodies used in this study

Drug combination pharmacokinetic parameters

Preclinical data: combination of low doses of camonsertib and gemcitabine. A, Cell viability (as measured by CTG) of RPE1 TP53-KO ATM-WT or ATM-KO cells after indicated treatments. B, In vitro, low doses of camonsertib and gemcitabine elicit sensitivity in ATM-deficient cells. ZIP combination scores in RPE1 TP53-KO ATM-WT or ATM-KO cells treated with indicated concentrations of cam and gemcitabine and processed for a CTG viability assay are shown. C, In vitro, low doses of camonsertib and gemcitabine elicit cytotoxicity in BRCA1-deficient cells. Viability of SUM149PT cells (BRCA1-mutant triple-negative breast carcinoma) as measured by a CTG growth assay. Cells were either left untreated or treated with 4 hours of gemcitabine, day 1, 2, or 3 of camonsertib, or combined camonsertib and gemcitabine. Compounds were then washed out, and viability was measured on day 8. D, Mice bearing Granta-519 tumors were treated with camonsertib (3/4 days weekly) or gemcitabine (once weekly) as single agents and in combination at the indicated doses. Tumor growth is represented as the mean ± SEM; n = 8 mice/group. Statistical differences between groups were determined using an unpaired t test with Welch correction. ***, P < 0.001; ****, P < 0.0001 (Prism v10.4). At termination of the experiment, complete blood counts were taken from all mice. E, Mean RBC, F, neutrophils, and G, platelets are shown ±SEM. Dashed lines represent normal range for age-, sex-, and strain-matched mice. Statistical differences were determined using one way ANOVA and Fisher LSD test (Prism v10.4). ns, not significant; *, P < 0.05; ****, P < 0.0001. Abbreviations: CTG, CellTiter-Glo; LSD, least significant difference; Max, maximum; PO, per-oral; QD, once daily; QW, once weekly; RBC, red blood cell.

Study schematic for TRESR, Module 4.

Figure S3 shows that p53 loss diminishes H3K9me3 at transcriptionally upregulated repetitive elements

3547 Background: Benefits of immune checkpoint inhibitors (ICIs) in unselected proficient mismatch repair (pMMR) mCRC remain unestablished. This exploratory analysis of CCTG CO.26 evaluated whether serum VEGF-A concentrations may influence ICI efficacy. Methods: CCTG CO.26 was a phase II trial that randomized refractory mCRC patients (pts) (2:1) to Durvalumab + Tremelimumab + Best supportive care (DT) vs Best supportive care (BSC) alone and was positive for overall survival (OS). VEGF-A concentrations were determined in baseline serum samples using an ELISA method. OS and progression-free survival (PFS) were compared between high and low groups based on median VEGF-A concentration in each treatment arm. An optimal cutoff was also identified using a minimal p-value approach. VEGFA mRNA expression from tissue-based RNA-seq was analyzed in the INSPIRE study, a separate, single arm, multicohort phase II trial comprising multiple tumor types treated with pembrolizumab for external validation. Results: Baseline VEGF-A concentrations were available for 161 pts (47 BSC, 114 DT). Median VEGF-A concentration was 1166 pg/ml (range: 226 – 4898; IQR: 784-1755). VEGF-A concentrations were significantly higher in ECOG 1 vs 0 pts (p = 0.03), and in pts who had previously received regorafenib (p = 0.03). Grouped by median VEGF-A, median OS was longer in DT-treated patients with low VEGF-A (7.39 months for DT-Low vs. 6.08 DT-high; hazard ratio (HR) 0.62, 95% confidence interval (CI): [0.42–0.90], p = 0.01), but not in BSC treated patients (4.44 months BSC-Low vs. 4.11 BSC-High; HR 1.05 [0.57–1.92], p = 0.88; interaction HR 0.56 [0.28–1.14], p = 0.11). An optimal VEGF-A threshold of 1540 pg/mL was identified using a minimal p-value approach, with 33.5% pts having high VEGF-A concentrations. Median OS was 7.29 vs 4.37 months for DT-Low and DT-High pts (HR 0.53 [0.35–0.80], p < 0.005), and 3.55 vs 7.46 months for BSC-Low and BSC-High pts (HR 1.50 [0.80–2.80], p = 0.21; interaction HR 0.33, [0.16–0.70], p < 0.005). In multivariable analyses incorporating ECOG, presence of liver metastases, plasma tumor mutation burden and arginine levels, low VEGF-A concentrations remained statistically associated with improved OS with DT (HR 0.46 [0.30–0.70], p < 0.001; interaction HR 0.18 [0.083–0.41], p < 0.0001). There was no association between VEGF-A concentrations and PFS in any arm. In the INSPIRE study (n = 66), VEGFA mRNA expression was lower in responders (p < 0.001) and significantly associated with improved PFS (HR 0.45 [0.25–0.79], p = 0.006) and OS (HR 0.47 [0.26–0.85], p = 0.013) across tumor types. Conclusions: Refractory mCRC patients with low VEGF-A concentrations may derive benefit from ICIs. This is the first report to suggest that serum VEGF-A concentration is a potential predictive biomarker for benefit from ICIs. These findings should be prospectively validated.

Abstract Introduction: RP-6306 (lunresertib), a first-in-class oral PKMYT1 inhibitor, exploits G2/M checkpoint dependence in TP53-mutant tumors and synergizes with chemotherapy preclinically, particularly in CCNE1-amplified backgrounds. TP53 mutations occur in ∼96% of HGSOC and ∼90% of serous EC. This phase I trial evaluated RP-6306 with carboplatin/paclitaxel in recurrent p53-abnormal gynecologic malignancies. Methods: Patients were eligible for carboplatin/paclitaxel rechallenge if disease recurred ≥3 months after prior platinum-based chemotherapy. Using a 3+3 design, patients received oral RP-6306 40 mg BID during week 1 (DL1) or weeks 1–2 (DL2) of each 21-day cycle, with carboplatin AUC5 and paclitaxel 175 mg/m2 on Day 1. Endpoints included MTD, RP2D, and safety. Cyclin E1 IHC (H-score) and paired Cycle 2 Day 2 biopsies (pCDK1 Thr14, γH2Ax) assessed biomarkers and pharmacodynamics. Results: Six patients enrolled (4 HGSOC, 1 carcinosarcoma of the ovary, 1 serous EC; median age 65; median 2 prior regimens). No DLTs occurred. DL2 was declared the RP2D. Common AEs were nausea, neutropenia, and diarrhea; grade ≥3 neutropenia in 2/3 (DL1) and 1/3 (DL2). ORR was 66% (4/6) and DCR 83%, with median PFS 6.7 months and DoR 5.5 months. All four Cyclin E1-high patients (H-score ≥100) achieved partial response; both H-score <100 patients had stable disease (p=0.066). Paired biopsies showed reduced pCDK1 Thr14 in 3/4 and increased γH2Ax in 2/4. Conclusion: RP-6306 with carboplatin/paclitaxel was feasible and well tolerated; the RP2D is 40 mg BID weeks 1–2 of each 21-day cycle. Cyclin E1-high tumors responded to this combination, supporting CCNE1 expression as a candidate predictive biomarker. These data provide proof-of-concept for PKMYT1 inhibition to potentiate platinum/taxane efficacy in p53-abnormal gynecologic cancers. Citation Format: Laura Venegas, Pamela Soberanis, Amit Oza, Ana Veneziani, Vikas Garg, Liana Lage, Valerie Bowering, Janelle Ramsahai, Stephanie Kwok, Ibtisam Rauf, Navjot Sidhu, Benito Czin Czin, Shiyi Chen, Stephanie Lheureux. Phase I study of the PKMYT1 inhibitor RP-6306 (lunresertib) in combination with carboplatin and paclitaxel for recurrent p53-abnormal ovarian and uterine cancer (GyneRep / OZUHN-019) [abstract]. In: Proceedings of AACR Drug Discovery and Development (AACR D3) Conference; 2026 Jul 21-24; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(14_Suppl):Abstract nr A059.

Figure S2 shows that Trp53 mutation facilitates transcriptional dysregulation of retrotransposons in murine oviductal epithelial cells and ovarian surface epithelial cells.

Figure S1 Shows that TP53 mutation facilitates transcriptional dysregulation of retrotransposons in STICs and human fallopian tube secretory epithelial cells

Purpose: The utility of combination treatment with gemcitabine and camonsertib, an ataxia telangiectasia and Rad3-related kinase inhibitor, in mediating tumor cell death was assessed in preclinical models, prompting clinical investigation. The phase Ib TRESR study (NCT04497116) aimed to evaluate the safety, tolerability, and preliminary efficacy of the combination in patients with advanced solid tumors harboring DNA damage repair (DDR) gene alterations.Patients and Methods: Cell lines and tumor xenografts were tested across a range of dose levels and schedules. Patients (N = 76) harboring tumors with DDR gene alterations received camonsertib (80-120 mg) and de-escalating gemcitabine (1,000-100 mg/m2) in 21- or 28-day cycles on an intermittent dosing regimen. Safety, tolerability, and preliminary efficacy were assessed to identify an optimal dosing regimen.Results: In preclinical models, low-dose camonsertib (1/3 maximum tolerated dose) and gemcitabine led to tumor regression and was well tolerated with minimal body weight loss observed. In patients, synergistic toxicities were observed, primarily myelosuppression, resulting in gemcitabine de-escalation. The introduction of a 1 week on/1 week off schedule in combination with low-dose gemcitabine allowed for spontaneous neutrophil recovery, fewer dose modifications, and improved tolerability. Tumor responses were primarily observed in patients with gynecologic cancers, with tumor control maintained for greater than 1 year in some patients.Conclusions: Camonsertib and low-dose gemcitabine demonstrated preliminary clinical activity, but due to challenging tolerability, further evaluation is warranted to identify the optimal dosing regimen and subset of patients who may benefit most from this combination.

Endogenous retrotransposable elements (EREs) can modulate immune responses. We explored ERE transcription in relation to response to immune checkpoint inhibition in advanced solid tumors. ERE expression was measured in pre and on-treatment samples from patients treated in a clinical trial with pembrolizumab. We evaluated immune cell infiltration and correlated ERE expression with interferon-stimulated gene profiles and cytolytic activity. Two independent datasets were retrospectively analyzed as external validation. ERE transcription, notably Alu followed by LINE elements, is upregulated in immunotherapy responders, and higher ERE expression correlates with durable clinical benefit and improved long-term outcomes. In responders, this dynamic increase correlates with CD8+ T cell infiltration and cytolytic activity, particularly during treatment. A trend towards increased A-to-I RNA editing was observed in responders. External validation in melanoma and non-small cell lung cancer cohorts confirmed a consistent pattern in ERE transcription. Therefore, ERE transcription is as a potential biomarker for personalized immunotherapy in solid tumors.

We report a rare case of a young patient (VENUS 167) initially diagnosed with grade 1 endometrioid endometrial cancer, which, following endocrine treatment, presented with mixed aggressive carcinoma with three distinct histologic patterns: grade 1 endometrioid, large cell neuroendocrine, and undifferentiated carcinoma. The surgical specimen at the time of disease progression was used to establish OPTO.85, a patient-derived organoid (PDO), followed by a corresponding organoid-derived xenograft (ODX). Multi-omic analyses confirmed that OPTO.85 accurately reflected the patient's tumor characteristics. Whole-exome sequencing analysis identified oncogenic alterations in PIK3CA, ARID1A, and CTNNB1. Further RNA sequencing and assay for transposase-accessible chromatin using sequencing analyses revealed enrichment in VEGF and Wnt signaling pathways, suggesting therapeutic vulnerabilities. A high-throughput drug screen was conducted using ApexBio-approved and epigenetic drug libraries, along with kinase inhibitor and tool compound libraries developed at the Ontario Institute of Cancer Research. The OPTO.85 PDO exhibited sensitivity to PI3K inhibitors and responsiveness to VEGF inhibition. Cediranib demonstrated synergy with BKM120, significantly reducing organoid growth. This combination also showed in vivo efficacy in the ODX model, in which dual inhibitors significantly suppressed tumor growth compared with single compounds. This case exemplifies the impact of genomic profiling and patient-derived models in identifying actionable molecular changes in rare cancers with limited therapeutic options and poor prognosis. It highlights that high-throughput sequencing for individual patient tumors and generation of patient-derived models are feasible in endometrial cancer. This preclinical model may assist clinical decision and personalized therapy requiring validation in prospective studies. SIGNIFICANCE:This study characterizes a rare aggressive mixed endometrial carcinoma that developed after hormonal therapy. Patient-derived organoid and xenograft models revealed actionable targets in the VEGF and PI3K pathways. Combined cediranib and BKM120 treatment showed synergistic antitumor effects in vitro and in vivo. These findings highlight the potential of integrating molecular profiling and drug testing to guide personalized therapies in rare and recurrent endometrial cancers.

Immunotherapy has significantly improved the treatment of metastatic solid tumors; however, detecting early signs of response to enable timely intervention for resistant tumors remains challenging. A blood-only circulating tumor DNA (ctDNA) test may provide a rapid assessment of tumor response without reliance on matched tumor tissue. We applied a tissue-agnostic, genome-wide methylation enrichment assay, based on cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq), to plasma samples from patients in a phase 2 trial evaluating pembrolizumab across multiple solid tumors (NCT02644369). A decrease in ctDNA from baseline to pre-cycle 3 was significantly associated with higher objective response and clinical benefit rates and longer progression-free and overall survival in univariate analyses, with these associations remaining significant in multivariable models except for overall survival. These results validate a commercial-grade, tissue-agnostic plasma cfDNA methylation platform for immunotherapy response monitoring, which may facilitate earlier, more informed treatment decisions and improve patient outcomes.

VENUS 167 Supplementary Table 2-HTS Drug Data

Abstract Background: Zedoresertib (zedo) and lunresertib (lunre) are oral, highly selective WEE1 and PKMYT1 inhibitors, respectively. Inhibition of these targets leads to premature mitotic entry, and in the presence of high replication stress causes mitotic catastrophe. In preclinical models, the combination of the zedo and lunre is synthetically lethal, supporting this first-in-class trial combination (NCT04855656). Methods: In this Phase 1 trial, patients (pts) with advanced solid tumors with CCNE1 amplification (amp), or FBXW7 or PPP2R1A deleterious mutations (mut) were treated with zedo (daily dosing) plus lunre (3 days on/4 days off), guided by preclinical modelling of the pharmacological contributions of WEE1 and PKMYT1 inhibition in achieving tumor regression. Objectives included safety, tolerability, recommended doses (RD), pharmacokinetics (PK), pharmacodynamics (PDy), antitumor activity and molecular response rate (MRR; ≥50% decline in circulating tumor DNA). Results: As of 18 Nov 2025, 54 pts (55.6% female ; prior lines of therapy 1 - 9, main cancer types: ovarian (OC) (35.2%), colorectal (31.5%), pancreatic (7.4%) and breast (5.6%)) were treated at 5 dose levels (DL) from 150 mg to 260 mg of zedo plus 60 mg or 80 mg of lunre. The most common ≥G3 treatment related adverse events (TRAEs) were anemia (9.3%), neutropenia (7.4%) and Palmar Plantar Erythrodysesthesia (PPE) (7.4%). There were no G5 TRAEs. 4 (9.3%) of 54 pts had a dose-limiting toxicity (G3 pain in extremity and G1 rash in same pt (zedo 150 mg / lunre 60 mg), G3 rash (200 mg / 80 mg), G3 PPE (260 mg / 60 mg), G3 vomiting (260 mg / 60 mg)). PK/PDy analyses showed dose-dependent exposures for both zedo and lunre and target engagement in most pts, with reductions in pCDK1 Thr14 and Tyr15 and yH2AX induction. 24 (55.5%) of 44 RECIST v1.1 evaluable pts showed tumor shrinkage (3 cCR, 5 uPR, 15 SD and 1 PD). Of 16 evaluable pts with advanced OC (12 platinum resistant , 2 unknown and 2 platinum sensitive) with CCNE1 amp (13 pts) or FBXW7 mut (3 pts), 13 (81.3%) showed tumor shrinkage (3 cCR, 3 uPR and 7 SD); clinical benefit rate (pts with CR, PR or SD) was 93.8%; 7 (43.8%) OC pts were on treatment for at least 16 weeks; 4 (25%) OC pts achieved GCIG CA-125 responses. Of 23 pts with a post baseline ctDNA analysis, a MRR of 39% was seen across all DLs. Conclusion: We report the first disclosure of clinical data of the first-in-field synthetic lethal combination of WEE1 and PKMYT1 inhibitors in a molecularly defined pt population. The safety profile of zedo and lunre was expected and manageable. Promising antitumor activity was observed in pts with CCNE1 amp or FBXW7 mut solid tumors, especially pts with OC. Further dose optimization of this combination is ongoing. Citation Format: Timothy A. Yap, Rahul Aggarwal, Elisa Fontana, Martin Hojgaard, Benedito A. Carneiro, Linda Duska, Patricia LoRusso, Siddhartha Yadav, Stephanie Lheureux, Cara Mathews, Ryan H. Moy, Nehal Lakhani, Mia Weiss, Joan Tymon-Rosario, Gerardo Colon-Otero, Ignacio Garrido-Laguna, Elisabeth K. Lee, Esteban Rodrigo Imedio, Jonathan Wessen, Luke Piggott, Vito Dozio, Noemie Luong, Christophe Mas, Alison M. Schram. First data disclosure of the Phase I trial of the first in class combination of WEE1 inhibitor zedoresertib with PKMYT1 inhibitor lunresertib in patients with advanced solid tumors harboring CCNE1, FBXW7, or PPP2R1A genomic alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT022.

3091 Background: G-quadruplexes (G4) are guanine-rich DNA/RNA structures that contribute to DNA damage and genomic instability. Pidnarulex (CX-5461) is a first-in-class G4 stabilizer that induces synthetic lethality in Homologous Recombination-deficient (HRD) cells. Previous phase 1 study showed safety and preliminary activity. Here we report dose optimization for recommended phase 2 dose (RP2D) of CX-5461 and confirm safety. Methods: CX-5461 was administered intravenously on Days 1 and 8 of a 28-day cycle at 2 dose levels (250 and 325 mg/m²) in patients (pts) with advanced pancreatic adenocarcinoma (PA), breast cancer (BC), or ovarian cancer (OC). The main cohort (Arms A: 250 mg/m² & B: 325 mg/m²) included pts with HRD or DNA damage response (DDR) alterations and has completed accrual. An exploratory cohort (Arms C: 250 mg/m² & D: 325 mg/m²) of OC pts with BRCA or other HRD genes enrolled simultaneously. Primary objective is to determine RP2D of CX-5461 using Relative Dose Intensity (RDI). Secondary objectives are safety, tolerability and efficacy. Results: 54 pts were treated and evaluable for toxicity (Arm A = 18, Arm B = 18, Arm C = 10, Arm D = 8). Patients’ characteristics and efficacy results are detailed in table 1. The median number of prior lines of treatment were 6 (1-14). The median number of CX-5461 cycles received were 2 (1-30) and weeks on treatment were 8 (4-120). Grade ≥3 Treatment-Related Adverse Events (TRAEs) occurred in 12 pts (22%), including proteinuria, thrombocytopenia, and fatigue; 6 (11%) were AEs of special interest: 1 (2%) palmar-plantar erythrodysesthesia, 4 (7%) photosensitivity, and 1 (2%) phototoxic drug eruption. Among 29 response-evaluable pts in main cohort, 1 had PR (3%) and 10 had SD (34%),median duration 16 weeks (wks) (8-84). In evaluable OC (n=29), 2 had PR (7%), 13 SD (44%), median duration 16 wks (8-84). OC pts with BRCA mutations (n=25) had 2 PR (8%) and 11 SD (44%); all had prior PARPi exposure. 3/ 5 non-BRCA HRD had SD (60%). Prolonged clinical benefit was observed in 4 pts with treatment durations of 14 (OC, gBRCA1), 17 (OC, gBRCA2), 21 (OC, sBRCA1) and 30 cycles (PA, gPALB2). RDI was 91% in Arm A and 88% in Arm B. RDI and clinical data support 250 mg/m² as the RP2D. Conclusions: CX-5461 was tolerable and showed evidence of durable disease control in heavily pretreated pts, enriched for HRD/DDR alterations and post exposure to PARPi. The 250 mg/m² dose is established as the RP2D based on clinical data and RDI. Correlative studies are ongoing. Clinical trial information: NCT04890613 . Arm A (N=18) Arm B (N=18) Arm C (N=10) Arm D (N=8) Tumor Type BC 7 (39%) 2 (11%) - - OC 5 (28%) 9 (50%) 10 (100%) 8 (100%) PC 6 (33%) 7 (39%) - - Molecular alterations gBRCA1/2 12 (67%) 9 (50%) 3 (30%) 3 (38%) sBRCA1 0 (0%) 1 (6%) 6 (60%) 3 (38%) Other 6 (34%) 8 (44%) 1 (10%) 2 (25%) Efficacy (evaluable pts only) PR 1/13 (8%) 0 (0%) 0 (0%) 1/7 (14%) SD 4/13 (31%) 6/16 (38%) 5/9 (56%) 3/7 (43%) Disease control rate 5/13 (39%) 6/16 (38%) 5/9 (56%) 4/7 (57%)

Kaplan-meier estimate for A, DOT and B, PFS in patients with and without reversions enrolled on LoF in BRCA1/2, RAD51p, or PALB2 in HRD associated tumor types (breast, prostate, pancreatic, ovarian) C) On-treatment BRCA1 reversion detected (RECIST and ctDNA cTF in Fig. 3D)

12074 Background: Routine early palliative care (EPC) for patients with advanced cancer improves quality of life. To increase scalability, models of triggered EPC have been encouraged. We assessed feasibility of hybrid virtual/in person Symptom screening and Targeted Early Palliative care (STEP2) to provide EPC triggered by symptoms. Methods: Patients with advanced cancer, ECOG 0-2, prognosis 6-36 months, were recruited from lung, gastrointestinal, genitourinary, breast and gynecology outpatient oncology clinics. Symptoms were screened virtually/in person ≤48 hours before oncology visits using Edmonton Symptom Assessment System-revised (ESAS-r+). Moderate to severe symptom scores (“screen positive”) triggered an alert to a nurse, who called the patient, offering an EPC visit (in-person/virtual, as per patient preference). Participants completed measures at baseline, 2, 4, and 6 months. The primary endpoint was feasibility, with the following criteria: ≥40 patients accrued in 4 months; ≥60% complete screening for ≥70% of visits; ≥50% triggering a call have ≥1 EPC visit; ≥60% complete all measures. Results: From 30/03/2025-26/06/2025 40 patients were enrolled (median age [range], 62 [39-88]; 21/40 [53%] female). Disease site distribution was: 12/40 (30%) lung, 9/40 (23%) gynecology, 8/40 (20%) genitourinary, 6/40 (15%) gastrointestinal, 5/40 (13%) breast. Of the 40 patients enrolled, 36 (90%) completed screening for ≥70% of visits and 29 (73%) screened positive: 18 at baseline and 11 later during the trial. The most common triggering symptoms were anxiety (18/29, 62%), sleep (17/29, 59%), depression (10/29, 35%), pain (8/29, 28%), and dyspnea (8/29, 28%); 21/29 (72%) screen-positive and 0 screen-negative patients received EPC before trial end. Measure completion at 2, 4, and 6 months was 90% (36/40), 85% (34/40), and 83% (33/40). Initial EPC visits were in person for 14/21 (67%) and virtual for 7/21 (33%); 20/21 (95%) of patients received ≥2 follow-up visits. Results for measures at baseline and at trial end are shown in the Table. Conclusions: Virtual/in person STEP2 is feasible and directs EPC to those who most need it, with most screen-positive patients accepting EPC. A phase III trial is underway. Clinical trial information: NCT06326554 . Variable Measure (score range) Time point N Mean Standard Deviation Difference, 6 mo. vs. baseline (95% CI) Quality of life FACIT_PAL14 Baseline 40 42.2 7.2 0.3 (0-56; higher is better) 6 mo. 34 42.7 7.7 (-0.9, 1.6) Symptom ESAS_EDS Baseline 40 17.5 12.9 0.3 Control (0-90; higher is worse) 6 mo. 33 18.9 13.2 (-3.1, 3.7) Depression PHQ-9 Baseline 40 5.4 3.4 -1.0 (0-27; higher is worse) 6 mo. 34 4.6 3.1 (-1.9, 0.0) Anxiety GAD-7 Baseline 40 4.9 3.8 -1.4 (0-21; higher is worse) 6 mo. 34 3.7 3.5 (-2.3, -0.5) Satisfaction FAMCARE-P16 Baseline 40 72.8 7.2 -5.8 With care (16-80; higher is better) 6 mo. 34 67.1 12.0 (-10.1, -1.4)

Treatment-emergent DLT adverse events