Background: Circulating tumors cells (CTCs) are considered an early step towards metastasis and have been linked to poor prognosis in several types of cancer. CTCs in squamous cell carcinoma of the head and neck (SCCHN) have an unclear role. Methods: In this prospective study, patients with locally advanced or metastatic SCCHN had CTC counts assessed before starting systemic treatment using the Cel-lSearch System. Select cases also had sequential CTC evaluation. Presence of CTCs was correlated with patient characteristics and outcomes. Results: Forty-eight patients enrolled, and 36 had evaluable clinical data and baseline CTC counts. Twenty-five patients had locally advanced disease (LAD) and 11 had metastatic disease. ≥1 CTCs were detected in six patients with LAD (24%) and four with metastatic disease (36%). On univariate analysis, smoking was associated with CTCs. Conclusion: CTCs are not associated with prognosis in patients with LAD and metastatic disease; however, they are present in this patient population, and ≥1 CTCs is associated with a history of smoking.
4156 Background: Targeting a molecular subset of pancreatic cancer (PC) may identify alternatives to perpetual chemotherapy and chemo-resistance/toxicity. Poly (ADP ribose) polymerase inhibitors (PARPi) have shown efficacy in germline BRCA mutation via synthetic lethality. Preclinical evidence suggests PARPi may target DNA repair defects beyond BRCA. We conducted a Niraparib phase II study in PC patients with germline/somatic DNA repair defects. Methods: This is an open-label, phase 2 trial in pts with locally advanced or metastatic PC with germline or somatic mutations , known or tested after consent to pre-screening tumor tissue analysis in DNA repair genes (BRCA1/2, PALB2, ATM, NBN, ATR, BRIP1, IDH1/2, RAD51, RAD51B/C/D, RAD54L, CDK12, BARD1, FAM175A, BAP1, CHEK1/2, GEN1, MRE11A, XRCC2, SHFM1, FANCD2, FANCA, FANCC, FANCG, RPA1, ARID1A), who have progressed on or intolerant of at least one line of therapy, no prior PARPi, with evaluable disease, and ECOG PS 0-1. Eligible pts were treated with Niraparib 300mg or 200mg PO daily for 28 days (1 cycle = 28 days) (200mg dose for baseline weight is < 77 kg or baseline platelet count is < 150,000 µL) until disease progression, unacceptable toxicity, investigator decision, withdrawal of consent, or death. The primary objective was 6-month PFS rate. The secondary objectives were OS, DCR and safety. Pts were evaluable for safety if they had received > 1 dose of Niraparib and for efficacy if they had also received > 1 follow-up imaging study. Results: As of Feb 2023, 36 (13 female, 23 male) pts were enrolled, with a mean age of 62.9 (median 64, IQR 51-73, min 41, max 83, SD 11.25), of whom 27 (8 female, 19 male) were evaluable for efficacy. After a median follow-up of 9.0 months (IQR 6.0-15.1 m), the 6-month PFS rate was 40.7% (11/27 pts; 95% CI 4.7%- 100 %). The median PFS is 4.4 m (CI 2.3 - 6.5 m), and median OS is 9.1 m (7.5 -15.1 m). The disease control rate at 8 weeks was 70.4% (19 of 27 pts; 95% CI 49.8%-86.3%). Of the 27 evaluable pts- BRCA2 mutation was seen in 10 pts, ATM (5), CHEK2 (5), BRCA1 (2), NBN (2), ARID1A (1), FANCA (1), FAM175 A (1), RAD51B (1), IDH1 (1), IDH2 (1). Among 36 pts evaluable for safety, treatment-related adverse events occurred in 75% (27/36), and Grade 3 and grade 4 treatment-related adverse events occurred in 31% (11/36). The most common treatment-related AEs were anemia (25%, 9/36), nausea (22%, 8/36), thrombocytopenia (19%, 7/36), vomiting (19%, 7/36), and fatigue (17%, 6/36). Serious treatment-emergent adverse events were reported in 11% (4/36). There were no treatment-related deaths. Conclusions: In previously treated pts with locally advanced and metastatic PC harboring DNA repair defects, niraparib monotherapy yielded a 6-month PFS rate of 40%, median PFS of 4.4 months, and median OS of 9.1 months. Clinical trial information: NCT03553004 . [Table: see text]
TPS4205 Background: MRD detected by presence of circulating tumor DNA (ctDNA) after intended curative treatment is associated with high risk of relapse in pancreatic cancer. Early treatment of patients with presence of ctDNA after completion of surgery +/- adjuvant therapy may offer an opportunity to clear ctDNA and improve outcomes. TG01 is a RAS-neoantigen peptide vaccine adjuvanted by QS-21 (Stimulon) targeting the seven most frequent codon 12-13 RAS mutations. TG01 has previously demonstrated ability to activate mutant RAS specific CD4+ and CD8+ T-cell responses in vaccinated patients and repeated TG01 dosing in resected pancreatic cancer was found to be well tolerated and associated with a median OS of 33.4 months (95% CI 24.0, 45.8)1,2. Checkpoint inhibitors as single agents have not shown anti-tumor activity in pancreatic cancer, suggesting that a priming agent inducing tumor-specific T-cells may be required to support efficacy. Balstilimab is a human monoclonal antibody targeting programmed cell death protein 1 (PD-1) which is intended to reverse the immunosuppressive effects of this signaling pathway in the context of tumor immuno-surveillance by T-cells. Methods: Design: A two-arm, open-label, phase II randomized trial of TG01/QS-21 vaccine or TG01/QS-21 vaccine plus balstilimab (n=12 per arm, N=24) with surgically resected Stage 1-3 RAS mutant PDAC who are MRD+ following completion of standard adjuvant chemotherapy. Assay: MRD is detected by a commercially available ctDNA assay (Signatera, Natera). Somatic variants are identified by whole–exome sequencing of the primary tumor and the matched normal (whole blood) sample and a bespoke assay of up to 16 clonal, somatic variants are generated for each patient. This “tumor signature” will be monitored in plasma throughout the study. Treatment schedule: A priming phase of six vaccine administrations once every two weeks followed by a maintenance phase of administrations once every 8 weeks for up to 51 weeks. Balstilimab will be administered every 2 weeks for up to 51 weeks beginning at week 3. Imaging assessment will be done every 12 weeks. Eligibility: Surgically resected pancreatic adenocarcinoma with pathogenic RAS mutation, and no evidence of recurrent disease on baseline imaging. Inclusion criteria also include ECOG PS 0-1, and positive Signatera ctDNA MRD. Objectives: The primary objective is to assess the 6-month molecular disease control rate as defined by ctDNA stable, decreased or cleared. Secondary objectives include safety of TG01/QS-21 with or without balstilimab, 6 and 12-month DFS rate in each cohort, as well as correlation between the depth of molecular response and DFS. Exploratory: changes in clonality of RAS mutations and assess immune response. Enrollment is ongoing. 1) Gjertsen MK et al. Int J Cancer 1997, 72(5) 784-90. 2) Palmer DH et al. Br J Cancer 2020 122:971-77. Clinical trial information: NCT05638698 .
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