Slide 1: Outcomes of Advanced/Metastatic Breast Cancer Treated with Bria-IMT
Outcomes of Advanced/Metastatic Breast Cancer (aMBC) Treated with Bria-IMT, an Allogeneic Whole-cell Immunotherapy Presenter: Saranya Chumsri, Mayo Clinic Florida, Jacksonville, FL Carmen Julia Calfa1, Chaitali Singh Nangia2, Minal A. Barve3, Kendrith M. Rowland4, Ralph V. Boccia5, John George Knech
Slide 2: Key Takeaway
2 Key Takeaway • Bria-IMT regimen is an allogenic, off-the-shelf, GM-CSF secreting, whole cell-based cancer vaccine. • Randomized Phase I/II trial to evaluate safety and efficacy of immediate C1 vs. delayed C2 CPI with Bria-IMT regimen. • Promising results across breast cancer subtypes were observed
Slide 3: Background: Mechanisms of Immune Activation
3 Background: Mechanisms of Immune Activation Bria-IMT (SV-BR-1-GM) • Allogenic off-the-shelf whole cell-based cancer vaccine • Origin: Metastatic HR- HER2+ breast cancer • Modification: Secrete GM-CSF • Formulation: Irradiated Shelf life > 4 years Lacher et al. Frontier in Immunology 2018 PRESENTED
Slide 4: Bria-IMT Regimen
4 Bria-IMT Regimen Day -2 or -3 Day 0 Day 2 ± 1 • Cyclophosphamide • 1 x 106 SV-BR-1-GM • Interferon at inoculation 300 mg/m2 IV cells ID sites • Retifanlimab • If no immediate • IFNɑ-2b10,000 units 375 mg IV hypersensitivity, ID x 4 or 20 x 106 SV-BR-1-GM • PegIFNɑ-2a 0.1 mcg cells ID (thighs and I
Slide 5: Methods: Phase I/II Trial Design
5 Methods: Phase I/II Trial Design • Primary objective To determine the optimal timing of the checkpoint inhibitor (CPI) start (Immediate C1 vs. Delayed C2). • Secondary objectives To determine the optimal formulation of SV-BR-1-GM with or without IFNγ incubation. To determine ORR, 12-week CBR
Slide 6: Patient Demographics (N = 54)
6 Patient Demographics (N = 54) N (%) N (%) Age, Median (Range) 61 (38-81) years Prior systemic therapy, Median (Range) 6 (2-13) BMI, Median (Range) 28.1 (18.1-42.7) Previous therapies Race/Ethnicity • ADC 23 (44%) • White 42 (78%) • CPI 11 (20%) • Black 6 (11%) • CDK4/6 inhibitors 34 (63%) • Hispan
Slide 7: Results: ORR and CBR
7 Results: ORR and CBR • 12-week clinical benefit seen in 55% of evaluable patients in all subtypes of breast cancer. Duration of Response 8.6 9.7 - 7.4+ median (range) months (5.8 - 9.8) (5.8 - 9.8) Duration of Clinical Benefit 5.0 3.7 2.7 6.2 median (range) months (1.8 - 10.3) (1.9 - 10.3) (1.8 -
Slide 8: Results: PFS
8 Results: PFS PRESENTED BY: Saranya Chumsri, M.D. Professor of Oncology, Mayo Clinic Breast Disease Group Research Co-Chair
Slide 9: Results: Immediate C1 vs. Delayed C2
9 Results: Immediate C1 vs. Delayed C2 Progression Free Survival • There was no significant difference in Randomized Phase II in PFS between 2 arms Immediate C1: CPI starting at cycle 1, 2 days prior to SV-BR-1- 81% CPI at Cycle 1 CPI at Cycle 2 GM Median PFS, months 3.7 3.2 HR (95% CI) Delayed
Slide 10: Results: Formulations
10 Results: Formulations Progression Free Survival • SV-BR-1-GM has 2 formulations by SV-BR-1-GM Formulation Pulsed with IFNγ (IFNγ added in cell culture for 48 hours, then washed prior to harvesting/irradiation/cryopreservation) Without IFNγ 73.0% Without IFNγ With IFNγ Median PFS, • Patients t
Slide 11: Results: Intracranial Responses in 5/6 Evaluable Patients
11 Results: Intracranial Responses in 5/6 Evaluable Patients Patient Demographics (N=7) Patients with Intracranial Metastasis Median Median Median Median Median OS Prior Lines Prior lines Prior Age (months) of of therapy Surgeries Radiation 64 9 5 3 2 Median Sum of Intracranial Lesion Diameters (mm)
Slide 12: Results: CBR in ADC Resistant Patients
12 Results: CBR in ADC Resistant Patients Bria-IMT PFS vs Penultimate Therapy PFS in ADC-resistant patients • Extend subsequent PFS in patients who had previously failed various ADC Trastuzumab deruxtecan ( T-DXd), sacituzumab govitecan, and ado-trastuzumab emtansine (T-DM 1) Histology All Evaluab
Slide 13: Results: Adverse Events
13 Results: Adverse Events • Treatment with the Bria-IMT regimen was generally well tolerated. Most common AEs (>10% reported on Bria-IMT Regimen): Maximum Grade Total Related N (%) N (%) Grade 1 Grade 2 Grade 3 Grade 4/5 Fatigue 10 (18.5) 10 (18.5) 3 (5.6) 0 12 (22) Injection Site Reaction 16 (29.6
Slide 14: Correlative Studies: CD8 PET Imaging
14 Correlative Studies: CD8 PET Imaging • Bria-IMT combination therapy induced CD8+ T cell infiltration in metastatic breast cancer. PRESENTED BY: Saranya Chumsri, M.D. Professor of Oncology, Mayo Clinic Breast Disease Group Research Co-Chair
Slide 15: Correlative Studies: CTC and CAML
15 Correlative Studies: CTC and CAML • Patients with lower circulating tumor Median CTC =0 5.0 CTC >0 3.6 cells (CTC) and cancer-associated PFS, months HR (95% CI) 0.71 (0.35 - 1.43) P = .07 (n.s.) macrophage-like cells (CAML) after the first cycle of treatment had significantly improved PFS. CAML<1
Slide 16: Correlative Studies: DTH Response
16 Correlative Studies: DTH Response • Delayed type hypersensitivity (DTH) Progression Free Survival by DTH Response A test dose of SV-BR-1-GM administer prior to full dose Skin reaction (erythema/induration ) DTH positive DTH negative measured 48 hours post-dosing Median 3.6 2.4 PFS, months • A
Slide 17: Correlative Studies: Quality of Life (SF-36)
17 Correlative Studies: Quality of Life (SF-36) General Health Pain Relief General health scores significantly correlate Pain relief score changes from baseline significantly with disease control. correlate with disease control. PRESENTED BY: Saranya Chumsri, M.D. Professor of Oncology, Mayo Clinic
Slide 18: Phase III Study Design
18 Phase III Study Design Hurvitz et al. Poster Session TPS1137 – Breast Cancer – Metastatic 6/2/2024 9:00 am-12:00 PM PRESENTED BY: Saranya Chumsri, M.D. Professor of Oncology, Mayo Clinic Breast Disease Group Research Co-Chair
Slide 19: Conclusions
19 Conclusions • In heavily pretreated breast cancer patients, the BRIA-IMT regimen showed promising results across breast cancer subtypes. • HR+ (ORR 10%, CBR 59%), HER2+ (ORR 50%, CBR 100%), TNBC (CBR 36%) • CNS responses were observed. • Treatment is well tolerated, mainly fatigue (22%) and injec
Slide 20: References
20 References Lacher MD, and Bauer G, et al. SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4 + T Lymphocytes. Frontiers in Immunology, 2018, Volume 9, Article 776 Sailaja Kamaraju; Blaise Bayer; Mingjin Chang; Will
Slide 21: Results: Intracranial Responses
21 Results: Intracranial Responses MRI showing complete response of orbital lesion MRI showing ongoing regression of orbital lesion Subject 1 Subject 2 Figure courtesy of Russ Kuker MD, U Miami PRESENTED BY: Saranya Chumsri, M.D. Professor of Oncology, Mayo Clinic Breast Disease Group Research Co-Ch