Barve, Minal

e13124 Background: Bria-IMT, an allogeneic whole-cell cancer vaccine (SV-BR-1-GM), was administered w/ an anti PD1 checkpoint inhibitor (CPI) to evaluate its safety and efficacy in advanced/metastatic breast cancer (MBC). SV-BR-1-GM breast cancer cells were engineered to directly stimulate anti-tumor immunity through expression of tumor associated antigens and secretion of GM-CSF to enhance endogenous dendritic cell activation. Addition of a CPI potentiates SV-BR-1-GM action by overcoming the immune suppressive tumor microenvironment and may have a differential impact vs monotherapy SV-BR-1-GM. Methods: In this exploratory analysis of the Phase 1 + randomized Phase 2, HLA matching status was assessed to explore potential correlations w/ clinical outcomes. Pts were stratified by overall HLA match by Class I or II (0 vs ≥1 matches), formulation and MBC subtype to assess objective response rate (ORR), clinical benefit rate (CBR), progression free survival (PFS), and overall survival (OS). Partial HLA matching (≥1 Class I and ≥1 Class II allele) was also analyzed. Results: In the total pt population, the ORR was 10%, CBR 56%, PFS 3.2 months and OS 9.9 months. In those pts treated w/ the phase 3 formulation, ORR was 15%, CBR 63%, PFS 3.6 months and OS 13.4 months. Using available HLA data (n = 52), 25% had 0, 34.6% 1, 32.6% 2, and 8% ≥3 matches. While OS and PFS were greater (Undefined vs 8.5 mos ; p = .02) in pts without an HLA match compared w/ those w/ ≥1 match (see Table), ORR and CBR were similar. This was also the case for pts who had 0 HLA Class I matches vs those w/ ≥1 Class I match (15.6 vs 7.2 mos; p = .002). ORR, CBR, PFS and OS were generally similar for pts who had 0 Class II HLA matches vs those w/ ≥1 match. Pts who matched at least at 1 Class I and 1 Class II allele had a higher ORR and CBR than those who matched at a single Class I or a single Class II allele although PFS and OS were similar between the groups. Similar observations were seen for pts treated w/ the phase 3 formulation. Conclusions: Matching at Class I seemed to decrease PFS & OS, but did not have a similar effect on ORR and CBR. Both matched and non matched pts demonstrated favorable OS and response rates. These findings support further investigation into specific mechanisms and the clinical significance of HLA matching in immunotherapy response. A randomized phase 3 trial is ongoing comparing Bria-IMT vs treatment of physician's choice (NCT06072612). Clinical trial information: NCT03328026 . n (Evaluable) % of Cohort Best ORR Best CBR PFS OS Full Cohort 52 (41) 10% 56% 3.2 9.9 No Match (Overall) 13 (10) 25% 20% 60% 4.2 Undefined Any Match (Overall) 39 (31) 75% 6% 55% 3 8.5 MHC Class I No Match / Any Match 27 (20) / 25 (21) 52% / 48% 10% /10% 55% /57% 3.5 / 2.7 15.6 / 7.23 MHC Class II Any Match 27 (19) 52% 11% 63% 3.2 11.4 MHC Class I&II Match 13 (9) 25% 22% 77% 2.8 8.6 Phase 3 Formulation (N=35) 35 (27) 15% 63% 3.57 13.43 No Match (Phase 3 Formulation) 11 (9) 31% 22% 67% 5.6 Undefined MHC Class I&II Match (Phase 3 Formulation) 11 (7) 31% 29% 71% 2.7 7.23

1096 Background: Bria-IMT is a combination immunotherapy consisting of allogeneic whole cell cancer vaccine (SV-BR-1-GM) administered w/ immune checkpoint inhibitor (CPI). SV-BR-1-GM breast cancer cells are engineered to directly stimulate anti tumor immunity via expression of tumor associated antigens and secretion of GM-CSF to enhance dendritic cell activation. Addition of CPI potentiates SV-BR-1-GM to overcome the immune suppressive tumor microenvironment. Methods: This Ph I/randomized Ph II study evaluated the Bria-IMT regimen in pts w/ metastatic breast cancer; CTX (300 mg/m²) on day -2/-3, SV-BR-1-GM and CPI on Day 0, w/ low dose peg interferon α at inoculation sites on day 2 (±1) . Phase II pts were randomized 1:1 to receive CPI at cycle 1 or cycle 2. Two SV-BR-1-GM formulations (w/ vs w/o IFNγ incubation) were evaluated. Biomarkers included cancer-associated macrophage-like cells, circulating tumor cells, PD-L1 scores, and delayed-type hypersensitivity skin tests. Results: 54 pts (22 Ph I, 32 Ph II) enrolled; 11 received pembrolizumab, 44 retifanlimab (1 crossover). 33 (61%) pts were ER+/PR+/HER2-, 18 (33%) TNBC, 3 (6%) HER2+. Median OS, PFS, ORR, and CBR were evaluated against two pivotal Ph 3 trials, ASCENT 1 (SG in TNBC) and TROPiCS-02 2 (SG in HR+/HER2- MBC) (see Table 1). In randomized pts, C1 vs C2 CPI had PFS (3.7 vs 3.2 mos, P=0.09) and OS (11.4 vs 7.4 mos, P=0.19). Pts receiving Ph 3 formulation (w/o IFNγ; N=37) had greater PFS (3.6 vs 2.6 mos, P=0.01) and OS (13.4 vs 6.9 mos, P=0.01). Bria-IMT was well tolerated w/ no Tx related D/Cs. Conclusions: The Bria-IMT Ph 3 formulation cohort OS was comparable to ASCENT and TROPiCS-02 (13.43 vs 11.8, 14.4 mos), exceeding TPC arms (6.9, 11.2 mos). CBR (61%) compared favorably to ASCENT (40%) and TROPiCS-02 (34%); ORR (14%) matched or exceeded TPC arms (4%, 14%). These outcomes were observed in a more heavily pretreated population, demonstrating Bria-IMT’s clinical activity. Randomized Ph 2 results suggest efficacy and safety in heavily pretreated MBC, w/ no significant OS difference between C1 and C2 CPI initiation and 22% of pts still in active survival follow up. Superior outcomes w/ the Ph 3 formulation support its continued evaluation. A randomized Ph 3 trial is ongoing, comparing Bria-IMT vs treatment of physician’s choice (NCT06072612). Clinical trial information: NCT03328026 . Trial (Cohort) Age (Median, Range) Prior Therapies (Median) OS (Median, mos) PFS (Median, mos) ORR (%) CBR (%) Bria-IMT (Overall Cohort) 61 (38-81) 6 (2-13) 9.9 (1.8-30.3) 3.6 10% 55% Bria-IMT (Ph 3 Formulation) 62 (44-80) 6 (2-13) 13.43 (1.8-30.3) 3.6 (1.8-16.5) 14% 61% ASCENT (SG) 54 (27-82) 4 (2-17) 11.8 4.8 31% 40% ASCENT (TPC) 53 (27-81) 4 (2-14) 6.9 1.7 4% 8% TROPiCS-02 (SG) 57 (49-65) 3 14.4 5.5 21% 34% TROPiCS-02 (TPC) 55 (48-63) 3 11.2 4 14% 22% References: Bardia A et al. J Clin Oncol. 2024 May 20;42(15):1738-1744Rugo, Hope S et al. The Lancet, Volume 402, Issue 10411, 1423 – 1433.

Abstract Background: Bria-IMT™ is a combination immunotherapy consisting of allogeneic whole-cell cancer vaccine (SV-BR-1-GM) administered w/ immune checkpoint inhibitor (CPI). SV-BR-1-GM breast cancer cells have been engineered to directly stimulate anti-tumor immunity through expression of tumor-associated antigens and secretion of GM-CSF to enhance dendritic cell activation. Addition of CPI potentiates SV-BR-1-GM to overcome the immune-suppressive tumor microenvironment. Methods: This Phase I and randomized phase II combination study evaluated the Bria-IMT™ regimen: preconditioning w/ CTX (300 mg/m2) on day -2 or -3, SV-BR-1-GM inoculation and CPI administration on Day 0, and low-dose peg- interferon α at inoculation sites 2 (±1) day post-SV-BR-1-GM. Phase II pts were randomized 1:1 to receive CPI at cycle 1 (immediate) or cycle 2 (delayed). Two SV-BR-1-GM formulations (w/ and w/o IFNγ incubation) were evaluated. Biomarkers included cancer-associated macrophage-like cells (CAMLs), circulating tumor cells (CTCs), PD-L1 scores, and delayed-type hypersensitivity (DTH) skin tests. Results: 54 pts (22 in Phase I, 32 in Phase II) enrolled. 11 pts received pembrolizumab, 44 retifanlimab, w/ 1 pt transitioning from pembrolizumab to retifanlimab. Median age 61(38-81) years; median 6(2-13) prior regimens. 33(61%) pts were ER+/PR+/HER2-, 18(33%) TNBC, and 3(6%) HER2+. Bria-IMT regimen was well tolerated, w/ no attributable Tx D/C. 67% of adverse events grade 1-2; 13% ≥ grade 3 including pulmonary embolism, increased lipase, and dehydration. Median overall survival (OS) was 9.9 (1.8 - 30.3) mos w/ 13% of pts in active survival follow-up. Median progression free survival (PFS) was 3.2 (1.1-16.5) mos w/ 1 pt still in treatment (16.5 mos). Pts treated w/ ph 3 formulation (w/o IFNγ; N = 37) had significantly improved PFS (3.6 vs. 2.6 mos, P=0.01) and OS (13.4 vs. 6.9 mos, P=0.01); in evaluable pts, objective response rate was 14% and clinical benefit rate 61%. Randomized pts receiving ph 3 formulation had not reached median OS. In randomized pts, C1 vs C2 CPI initiation showed greater PFS (3.7 vs. 3.2 mos, P=0.09) and OS (11.4 vs. 7.4 mos, P=0.19). OS in pts w/ no HLA match was undefined vs 8.6 mos in pts w/ any match (P = 0.04). DTH (+) vs (-) correlated w/ greater OS (11.9 vs. 4.7 mos, P= <0.0001) and PFS (3.5 vs. 2.4 mos, P=0.001). Conclusion: Randomized phase 2 Bria-IMT demonstrated efficacy and safety in heavily pretreated MBC. Post-progression survival exceeding median OS in pts still undergoing survival follow-up suggests long-term benefit extending beyond treatment period. C1 vs C2 CPI initiation showed no statistical or clinically significant difference in OS. Superior outcomes w/ phase 3 formulation support its use in future trials. These results confirm earlier reports of the trial and an even greater benefit. A randomized phase 3 trial is ongoing comparing Bria-IMT vs treatment of physician's choice (NCT06072612). Trial Information: NCT03328026 Citation Format: Saranya Chumsri, Chaitali Nangia, Minal Barve, Kendrith Rowland, Ralph Boccia, John Knecht, Blaise Bayer, Marcela Salgado, Tamar Aghajanian, William V. Williams, Charles Wiseman, Giuseppe Del Priore, Carmen Calfa. Survival outcomes in a randomized phase 2 ofBria-IMT: An allogeneic whole cell cancer vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT100.

Background Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells promote a hostile tumor microenvironment and are associated with worse clinical outcomes in PROC. We evaluated the safety and preliminary efficacy of PY159, an agonist antibody to Triggering receptor expressed on myeloid cells-1 (TREM1) that reprograms immunosuppressive intratumoral myeloid cells, and PY314, an antagonist antibody to Triggering receptor expressed on myeloid cells-2 (TREM2) that depletes tumor-associated macrophages, as single agents and in combination with pembrolizumab in subjects with PROC. Methods PY159 and PY314 were individually evaluated in patients with PROC. Patients were treated with monotherapy (PY159 3 mg/kg or PY314 10 mg/kg), based on the recommended dose for expansion derived from the phase 1a studies. At the time of first progression, patients could continue study drug and crossover to combination therapy with pembrolizumab (200 mg) every 3 weeks at the discretion of the investigator. Disease assessment by Response Evaluation Criteria in Solid Tumor version 1.1 was performed every 6 weeks. Results 17 patients were enrolled in the PY159 study (median age 67, range 22–77; median prior therapies 6, range 2–18) and 16 patients in PY314 (median age 65.5, range 49–81; median prior therapies 4, range 2–10). 7 patients in PY159 and 8 patients in PY314 crossed over to combination therapy. Safety events included the following: treatment-related adverse events occurred in 15 patients (88.2%) in PY159 and 9 patients (56.3%) in PY314. Infusion-related reactions occurred in 6 patients (35.3%) in PY159 and 3 patients (18.8%) in PY314. Immune-related adverse events occurred in 13 patients (76.5%) in PY159 (arthralgias) and 1 patient (6.3%) in PY314 (diarrhea). Serious adverse events occurred in 6 patients (36.3%) in PY159 (1 related) and 12 patients (75%) in PY314 (all unrelated). The best radiographic response in PY159 was stable disease in 8/16 patients (50%; median 16 weeks, range 9–33), and in PY314, it was stable disease in 8/16 patients (50%; median 12 weeks, range 6–36). Median PFS was 2.76 months and 2.69 months in PY159 and PY314, respectively. There were no responses in the crossover arm. Conclusions Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as both single agents and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC.

131 Background: KRAS G12C mutations occur in 3%–4% of CRC cases and are associated with poor prognosis. In the phase 1/2 KRYSTAL-1 study (NCT03785249), at a median follow-up of 11.9 months (mo), Ada (irreversible inhibitor of KRAS G12C ) in combination with Cetux (anti-EGFR antibody) demonstrated promising clinical activity (objective response rate [ORR] of 34% per blinded independent central review [BICR] and 43% per investigator [INV]) and was well tolerated in patients (pts) with previously treated KRAS G12C -mutated mCRC. Based on these findings, Ada + Cetux was granted accelerated approval in the United States for these pts. Here, we present longer-term follow-up analyses from this study. Methods: Adults with previously treated KRAS G12C -mutated mCRC and ECOG performance status of 0 or 1 were treated with Ada (600 mg BID) in combination with Cetux (400 mg/m 2 followed by 250 mg/m 2 QW or 500 mg/m 2 Q2W) until disease progression, unacceptable toxicity, withdrawal of consent, or death, in separate phase 1 and phase 2 cohorts. Primary endpoints were safety (phase 1) and ORR per BICR (phase 2). Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (phase 2). Results: A total of 94 pts received Ada + Cetux. The median number of prior lines of systemic therapy was 3 (range, 1–9); 23 pts (24%) had received ≥ 4 prior lines of systemic therapy. The most frequent sites of metastases at baseline were the lung (71%) and liver (64%). At a median follow-up of 20.4 mo, ORR per INV was 43% (95% CI 32–53) and all were partial responses; median DOR was 5.9 (95% CI 5.5–7.6) mo. Disease control rate per INV was 86% (95% CI 78–92). Median PFS per INV was 6.9 (95% CI 5.9–7.4) mo; 6- and 12-mo PFS rates were 61% and 19%, respectively. Median OS was 16.0 (95% CI 13.3–18.8) mo; 6- and 12-mo OS rates were 88% and 66%, respectively. Any-grade treatment-related adverse events (TRAEs) were reported in 100% of pts, 28% of which were grade 3/4. TRAEs led to discontinuation in 10% of pts. Efficacy analyses by BICR, subgroup analyses, and additional safety results will be presented. Conclusions: In heavily pretreated pts with KRAS G12C -mutated mCRC, Ada + Cetux continued to demonstrate clinically meaningful activity and tolerable safety with longer follow-up. These updated results are consistent with those from the primary analysis and constitute the longest duration of follow-up for dual KRAS G12C /EGFR blockade in this setting. Efficacy of second-line Ada + Cetux vs chemotherapy in KRAS G12C -mutated mCRC is being investigated in the phase 3 KRYSTAL-10 study (NCT04793958). Clinical trial information: NCT03785249 .

3078 Background: Q901 is a potent, covalently binding CDK7 inhibitor with excellent specificity for CDK7 against other protein kinases. Transcriptional regulation by CDK7 inhibition in cancer cells leads to DNA damage repair response inhibition and increased genomic instability. Q901 also regulates cell cycle checkpoints by inhibiting T-loop phosphorylation and transcriptionally downregulating CDK1, 2 and 4. In preclinical in vivo models, intravenous (iv) administration of Q901 once a week and once every three-week dosing regimen was well tolerated and showed significant antitumor activity. The safety profile, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy data for 18, 36 and 60 mg/m2 are presented. Methods: QRNT-009 (NCT05394103) is an ongoing Phase 1/2 multicenter, open-label, dose escalation and expansion study. Q901 is administered iv once weekly for four weeks, then once every two weeks thereafter in patients with advanced or metastatic ovarian cancer, castration-resistant prostate cancer (CRPC), breast cancer, endometrial cancer, colorectal cancer, small cell lung cancer (SCLC), or pancreatic cancers. Results: As of data cutoff (12Jan2024), 17 patients received Q901 across 3 dose levels: 5 patients at 18 mg/m2, 4 patients at 36 mg/m2, and 8 patients at 60 mg/m2. The median prior lines of systemic therapy were 4 (range 2 - 17). Of 17 patients who received Q901 across all doses, there were no treatment related SAEs, treatment discontinuations, or dose reductions. Most common TRAEs ≥ 15% were nausea (29.4%), anemia (23.6%) and fatigue (23.5%). As of data cutoff, no DLTs were observed. All plasma PK analyses across dose levels showed dose dependent increase of AUC0-last and Cmax. No major metabolite was observed. POLR2A, which is a CDK7 target engagement marker showed biologically effective change starting from 18 mg/m2. 1 patient with pancreatic cancer who received 18 mg/m2 had a partial response with CA19-9 reduction from 4,632 to 219. 2 patients at 18 mg/m2 and 2 patients at 36 mg/m2 had stable disease. Additional safety and efficacy data will be presented. Conclusions: Preliminary data from QRNT-009 study showed that selective CDK7 inhibitor Q901 is well tolerated. Preliminary antitumor activity and pharmacodynamic observations are encouraging. Dose escalation is ongoing to identify MTD or recommended dose for further studies. Clinical trial information: NCT05394103 .

1022 Background: The Bria-IMT regimen is a combination immunotherapy using an allogeneic whole cell cancer vaccine combined with checkpoint inhibitors (CPIs). Intradermally administered irradiated SV-BR-1-GM breast cancer cells secrete GM-CSF and present tumor associated antigens (TAAs) on HLA-I and –II molecules to directly stimulate anti-tumor immunity. Anti-PD1 CPI further stimulates T-cells and synergizes with SV-BR-1-GM. Here we report the results of the phase 1/2 trial (NCT03328026) of Bria-IMT in metastatic/advanced breast cancer evaluating sequencing of SV-BR-1-GM inoculation and CPI. Methods: Analysis of the phase 1 with expansion phase 2 cohort randomized by sequence using SV-BR-1-GM, checkpoint inhibitor (pembrolizumab or retifanlimab), low dose cyclophosphamide (Day –2) and post-dose local pegylated interferon α, with cycles every 3 weeks. In the 1:1 randomized cohort, CPI is either dosed at C1 prior to SV-BR-1-GM (original sequence) or delayed to C2 post-SV-BR-1-GM (alternative sequence). Cancer-associated macrophage-like cells (CAMLs) and circulating tumor cells (CTCs) were monitored as biomarkers. Results: A total of 54 patients were dosed: 11 with pembrolizumab, 44 with retifanlimab (1 patient received pembrolizumab and later retifanlimab). Median age=61 (38-81); Median prior regimen=6 (2-13); 72% ER+/PR+/HER2-; 6% HER2+ and 22% triple negative. Bria-IMT regimen was well tolerated with only 9% drop-out rate due to AE. AEs related to IPs were seen in 74% of patients; the majority (91%) being grade 1-2, and few (1.7%) grade 4 cases including pulmonary embolism, dehydration and increased lipase. Among 30 patients with post-dose CAML/CTC data and evaluable outcome, CAML count <5 associates with disease control (p=0.06, Chi square test). Patients who developed DTH to SV-BR-1-GM had significantly better PFS and higher OS. Patients treated with phase III formulation had an increase in PFS. Quality of life improvement correlates with disease outcome and survival. Among the patients treated with the phase III formulation of SV-BR-1-GM (n=23 with evaluable outcomes), objective response rate (ORR) is 13% and disease control rate (DCR) is 61%, with median PFS and OS are 4.1 and 13.3 months, respectively. In the randomized portion, the original sequence cohort had higher DCR (43% vs 36%) and OS (P=0.08, HR 0.30, 95%CI 0.08-1.17) compared to the alternative sequence cohort. Conclusions: BRIA-IMT has shown a favorable safety profile while providing benefits to heavily treated aMBC patients. Superior outcomes and survival were seen in patients treated with the phase III formulation and regimen now being used in the ongoing Ph3 trial, confirming the improvement in efficacy of the novel regimen. The results from this randomized phase 2 study informed the study design of the ongoing Ph3 trial comparing BRIA-IMT to standard of care physician choice treatments (NCT06072612). Clinical trial information: NCT03328026 .

Abstract Introduction Despite progress in MBC, too many continue to succumb due to treatment resistance or intolerance. SV-BR-1-GM is an allogenic human breast cancer cell line with antigen presenting cell activity designed to overcome the immune-suppressive tumor microenvironment while being acceptable to extensively pretreated contemporary MBC patients. We report interim exploratory analysis of the ongoing RCT of the Bria-IMT regimens. Methods An interim exploratory analysis using preliminary partially available evaluable data of the ongoing prospective, randomized phase 2 (NCT03328026; 2018-present) of Bria-IMT (irradiated SV-BR-1-GM) with a PD-1check point inhibitor (CPI) every 3 weeks (25 patients dosed to date). Both regimens include cyclophosphamide 300 mg/m2 48-72 hours prior to intradermal Bria-IMT (~20 x 106 cells) followed by interferon-alpha at the inoculation sites 2 days later. The control arm used the original sequence with simultaneous start of Bria-IMT and CPI in cycle 1. The experimental arm started CPI in cycle 2 after the 2nd inoculation. Candida skin test was performed before cycle 1 to determine anergy status while delayed-type hypersensitivity skin test (DTH), defined as &gt;5mm erythema & induration, was done at every cycle by intradermal injection of a small test dose of Bria-IMT prior to full dose inoculation. Results Median age: 58 (range 37-81); median prior therapies: 8 lines (range 4-18); 89% were grade 2/3 (n=18); 68% hormone receptor positive; 61% HER2 negative, 33% HER2 low, and 6% HER2 high; 33% triple negative. Overall, 53% of subjects had a clinical benefit as best response by BICR, PI or target lesion measurement. The two treatment arms were similar with a trend showing longer median durations on therapy (mDOT) of 3.7 mo in the experimental delayed CPI arm compared with mDOT = 2.9 for original sequence control arm. 47% of patients were anergic to candida. Among all anergic subjects, the mDOT was 3.5 compared to 2.5 mo for non-anergic patients. However, among anergic subjects, the alternative treatment arm had a lower risk of treatment discontinuation (improved HR) with mDOT of 3.7 compared to the 3.3 mo mDOT of the original treatment. 50% of anergic subjects eventually developed DTH to SV-BR-1-GM. mDOT was 4.0 mo for DTH+ pts vs 3.0 mo for those who did not mount DTH. Median OS was not yet reached; mean OS was higher in non-anergic vs anergic pts. Among those who developed an inoculation site reaction to Bria-IMT, OS was greater than for those who did not. Time on the Bria-IMT regimen exceeded the time on penultimate treatment in 22% of subjects while 33% of subjects with prior CPI use exceeded last therapy. AEs were mild with 28% of subjects (n=7) having &gt; grade 3 events. The most common grade 3+ AE was lipase increase (n=3). One subject with encouraging changes in peripheral blood tumor markers and CTCs completed a PET study using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α (CD8 Immuno-PET) and demonstrated increased uptake in some metastatic lesions and draining lymph nodes. Updated results will be provided at the meeting. Conclusion Sequencing of CPI with Bria-IMT is associated with differential clinical outcome trends but not statistically significant in this interim preliminary exploratory analysis regardless of prior CPI use. Bria-IMT is immunogenic with clinical benefit demonstrated for both treatment schedules among patients with inducible DTH reactions. Patients who develop an immune response to Bria-IMT had an increase in OS compared to those who did not. The nodal localization of CD8+ cells on PET may indicate a systemic activation of CD8 positive lymphoid cells. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites. These preliminary results will be evaluated in the ongoing randomized phase 3 pivotal registrational trial. Citation Format: Carmen Calfa, Chaitali Nangia, Minal Barve, John Knecht, Jarrod Holmes, Kendrith Roland, Ralph Boccia, Frances Valdes-Albini, Zach Gostout, Mingjin Chang, William Williams, Charles Wiseman, Bonnie Guerin, Shaker Dakhil, Giuseppe Del Priore, Saranya Chumsri. Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-12.

Abstract Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four patients received adagrasib plus cetuximab. With a median follow-up of 11.9 months, ORR was 34.0%, disease control rate was 85.1%, and median duration of response was 5.8 months (95% confidence interval [CI], 4.2–7.6). Median progression-free survival was 6.9 months (95% CI, 5.7–7.4) and median overall survival was 15.9 months (95% CI, 11.8–18.8). Treatment-related adverse events (TRAEs) occurred in all patients; grade 3–4 in 27.7% and no grade 5. No TRAEs led to adagrasib discontinuation. Exploratory analyses suggest circulating tumor DNA may identify features of response and acquired resistance. Significance: Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or metastatic KRASG12C-mutated colorectal cancer. These data support a potential new standard of care and highlight the significance of testing and identification of KRASG12C mutations in patients with colorectal cancer. This article is featured in Selected Articles from This Issue, p. 897 See co-corresponding author Rona Yaeger discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932606282/f27a6e46f4

PURPOSEThere are numerous barriers to enrollment in oncology biomarker-driven studies.METHODSThe ELAINE 2 study (ClinicalTrials.gov identifier: NCT04432454 ) is an open-label phase 2 study of lasofoxifene combined with abemaciclib in patients with advanced or metastatic estrogen receptor–positive/human epidermal growth factor receptor 2–negative breast cancer with an ESR1 mutation. ELAINE 2 opened clinical sites by using a Traditional approach, which activated a site before patient identification, and the Tempus TIME Trial network, which opened a site only after identifying an eligible patient. This manuscript presents the operational metrics comparing the Traditional and TIME Trial site data.RESULTSThe study enrolled patients over 34 weeks and 16 sites (six Traditional and 10 TIME Trial) participated. Duration for full clinical trial agreement execution for Traditional sites and TIME Trial sites averaged 200.5 (range, 142-257) and 7.6 days (range, 2-14), respectively. Institutional review board approval time for Traditional sites and TIME Trial sites was 27.5 (range, 12-71) and 3.0 days (range, 1-12), respectively. Duration from study activation to first consent was 33.3 (range, 18-58) and 8.8 days (range, 1-35) for Traditional and TIME Trial sites, respectively. The first patient on study was at a TIME Trial site 115 days before a Traditional site and the first seven patients enrolled were at TIME Trial sites. Traditional sites consented 23 and enrolled 16 patients, while TIME Trial sites consented 16 and enrolled 13. The trial enrolled 29 patients in 8.5 months with the anticipated enrollment duration being 12-18 months.CONCLUSIONThe TIME Trial network opened earlier and enrolled the first study patients. These results demonstrate that the Just-in-TIME model, along with a Traditional model, can improve enrollment in biomarker-driven studies.