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1084 Background: A substantial benefit from adding an immune checkpoint inhibitor to chemotherapy (CT) was reported in mTNBC patients (pts) with PD-L1+ tumors. However, many pts still have a poor outcome. ATRACTIB is exploring the synergism between A (anti-PD-L1 antibody) and B (a VEGF-targeted antibody) with P in mTNBC irrespective of PD-L1 status. We report results from protocol-specified SIA. Methods: ATRACTIB is an open-label, single-arm, phase 2 trial (NCT04408118). Pts aged ≥18 years, with unresectable locally advanced or mTNBC, ECOG performance status of 0–1, who had received no prior systemic therapy or ≥12 months since (neo)adjuvant taxane-based CT are eligible. Pts receive A (840 mg IV, days 1, 15) with P (90 mg/m2 IV, days 1, 8, 15), and B (10 mg/kg IV, days 1, 15) on each 28-day cycle until disease progression, unacceptable toxicity, or patient withdrawal. Primary endpoint is investigator-assessed progression-free survival (PFS) as per RECIST v.1.1. Secondary endpoints include objective response and clinical benefit rates, overall survival, and safety. The trial was designed to detect a treatment effect in terms of median PFS (H0: ≤7 months; H1: ≥9.5 months) and 100 pts are needed to attain 80% power at a nominal one-sided α level of 5%. One SIA was planned for evaluating safety as per CTCAE v.5.0 on the first 20 pts who had completed a 3-month follow-up or reached the end of study. Results: From Oct 5, 2020, through Nov 21, 2021, 34 pts were enrolled at 13 sites in Spain and Germany and received at least 1 dose of study treatment. Median age was 57.5 (range 40–84) years, 23 (67.6%) pts had received prior CT for early disease, and 19 (56.0%) had visceral disease. At data cutoff (Sep 30, 2021), 25 (71.4%) pts were still receiving the drug regimen. Adverse events (AEs) led to drug discontinuation in 3 (8.8%) pts. Mean relative dose intensity was 90.2% for A, 96.5% for P, and 95.7% for B. P dose reduction was reported in 7 (20.6%) pts. Five (14.7) pts required a dose delay due to AEs (11.8% for A, 11.8% for P, and 8.8% for B). The most common AEs of any grade (G) were fatigue (47.1%; 8.8% G≥3), diarrhea (38.2%; 0% G≥3), and neurotoxicity (35.3%; 8.8% G≥3). Anemia (20.6%; 0% G≥3) and neutropenia (17.6%; 8.8% G≥3) were the most frequent hematological AEs. AEs of clinical interest (AECI) for B were hypertension (17.6%; 5.9% G≥3) and pulmonary embolism (2.9%; 0% G≥3). AECI for A were pneumonitis (2.9%; 0% G≥3), autoimmune hepatitis (2.9%; 2.9% G≥3), and alanine aminotransferase increased (2.9%; 2.9% G≥3). No treatment-related deaths were reported. Conclusions: The addition of A to P and B as 1L therapy for mTNBC shows a tolerable safety profile which is consistent with known safety profile of each agent without a significant synergistic toxicity. Based on the independent data monitoring committee recommendation, patient recruitment is ongoing. Clinical trial information: NCT04408118.

e19085 Background: Repeat biopsies of cancer p are useful for monitoring molecular evolution of the disease and the possible appearance or disappearance of key somatic mutations, particularly those...

1042 Background: Neoadjuvant chemotherapy is generally used for treatment of both early stage and locally advanced breast cancer. However, robust prognostic or predictive biomarkers are needed in t...

e22119 Background: Although it is know that pCR following neoadjuvant chemotherapy is more frequent in some subtypes of breast cancer such as Triple Negative (TN) or erb2 tumors, the predictive role of gene expression and mutation status is not well defined in this setting. Methods: We analyzed samples from 41 patients (p) prospectively treated with neoadjuvant chemotherapy (sequential AC followed by weekly TXL, or inverse sequence, plus trastuzumab for erb2 positive p). Pathologic response (PR) was classified according to Miller-Payne and RCB criteria. Radiologic evaluation was performed by ultrasonography, dynamic MR and PET-TAC after each chemotherapy sequence. We performed expression analysis of AXL, BRCA1, RAP80, BIM, EZH2, ROR1, FGFR1, PTPN12, YAP, GAS6, beta-TRCP, HIF1 alpha and ZNF217 by RT-PCR, and mutational status of p53 and PI3K genes in pretreatment biopsies. Statistical analysis was performed using Mann-Whitney U and Pearson’s chi-squared tests. Results: pCR was detected in 5 p (3TN, 2 erb2) of 25 p (9 luminal A, 5 luminal B, 6 erb2 and 5 TN) evaluated for PR at time of submitting this abstract. TN tumors had lower levels of RAP80 (p=.0013), PTPN12 (p=.003), beta TRCP (p=.001), ZNF217 (p=.014) and YAP (p=.097). Luminal B tumors had low levels of YAP and the highest levels of FGFR1 (p=.09) and ZNF217 (p=.014). Luminal A tumors had high levels of beta-TRCP (p=.003). We found no differences in BRCA1, AXL, BIM, EZH2, ROR1, GAS6 and HIF1 levels by breast cancer subtype. P with low levels of FGFR1 (p=.087), HIF1alpha (p=.07) or EZH2 (p=.005) had higher probability of pCR. No pCR was observed in p with higher levels of AXL, EZH2, RAP80, GAS6, beta TRCP, HIF alpha. Four p had p53 mutations (1 luminal B, 1 erb2 and 2 TN) and 4 p had PI3K mutations (2 luminal A, 1 erb2, 1 luminal B). There was no correlation between p53 status and PR. P with PI3K mutations did not achieve pCR vs 46% of p with wild type PI3K (p=.23). Conclusions: Gene expression profile varies by breast cancer subtype. Chemosensitivity could be higher in tumors with lower levels of FGFR1, HIF1alpha or EZH2. Further results will be presented.

e18137 Background: Advanced NSCLC p with EGFR activating mutations show an impressive progression-free survival (PFS) to erlotinib. The co-existence of the EGFR T790M mutation, in conjunction with high BRCA1 mRNA levels, affected PFS to erlotinib (Rosell et al. CCR 2011). LMO4 is a negative regulator of BRCA1 function in sporadic breast cancers, and CtIP can bind to BRCA1 and LMO4. We have assessed the expression of CtIP, LMO4 and BRCA1 and examined the impact of CtIP and LMO4 levels on outcome. Methods: mRNA expression of LMO4 and CtIP was examined by RT-PCR in the original pretreatment tumor biopsies of 81 NSCLC p with sensitive EGFR mutations. Results: Expression of BRCA1 and LMO4 was successfully assessed in 55 p: median age, 68; 61.8% female; 98.2% Caucasian; 63.6% never-smokers; 81.8% ECOG PS

e18143 Background: Advanced NSCLC p with EGFR mutations have a median PFS of 14 months (m) and OS of 27 m when treated with erlotinib. In NSCLC cell lines, tyrosine kinase inhibitors (TKIs) induce p53 translocation from the cytoplasm to the nucleus and subsequent upregulation of Fas and caspase activation leading to apoptosis, but this mechanism was defective in p53-null cells. We tested whether TP53 mutations influence outcome to erlotinib in EGFR-mutated p. Expression levels of the p53 repressor MDM2 were also examined. Methods: We assessed p53 status in pretreatment paraffin-embedded tumor samples from 93 erlotinib-treated, EGFR-mutated advanced NSCLC p. Mutations in exons 5, 6, 7 and 8 were screened by High Resolution Melting analysis followed by sequencing of the amplified products with non-wild-type (wt) melt curves. All mutant samples were re-confirmed by standard PCR and sequencing. Expression levels of MDM2 mRNA were determined by quantitative RT-PCR. Results: Mutations in exons 5-8 of TP53 were detected in 26 of 93 p (28%). We found an unusually high frequency of in-frame and frameshift deletions (23% of mutations), indicating that the spectrum of p53 mutations might be different in EGFR-mutated NSCLC. Mutations were less frequent in p with ECOG PS >2 and more frequent in p with the T790M mutation. OS was 15 m in the 16 p with missense mutations 31 m in p with wt p53 and not reached in p with non-missense mutations (P=0.04). PFS was 9 m for 14 p with mutations in one of the p53 DNA binding motifs (DBMs), compared to 19 m for wt p and 27 m for p with non-DBM mutations. MDM2 mRNA levels were significantly lower in tumors with p53 mutations, especially in DBM mutations. In the case of wt p, high MDM2 expression correlated with longer PFS and OS in p with wt p53. Conclusions: TP53 mutations co-exist with EGFR mutations in a significant number of p; missense mutations correlate with shorter OS and mutations in DBMs correlate with shorter PFS. This finding paves the way for the possibility of combining erlotinib with a drug restoring p53 function in those p harboring certain types of mutations in the TP53 gene.