Roche Holding Ltd · SIX:RO
Roche — Technical Presentation (2024)
20 slides from Roche's technical presentation, Jun 19, 2024
Slide 1: First-line inavolisib + palbociclib + fulvestrant: INAVO120 Phase III additional analyses
First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phas
Slide 2: Summary slide
Summary slide • INAVO120 met its primary endpoint, with a statistically significant and clinically meaningful improvement in PFS (15.0 months versus 7.3 months; hazard ratio, 0.43 [95% CI = 0.32, 0.59]; p<0.0001)1 • To allow further characterization of inavolisib-based treatment we report additional
Slide 3: Background
Background • More effective and tolerable treatments for patients with PIK3CA-mutated, HR+, HER2– advanced BC are needed1–3 • Preclinical data demonstrated substantial synergy upon simultaneous inhibition of the PI3K, CDK4/6, and estrogen receptor pathways in PIK3CA-mutated xenograft models by deepe
Slide 4: INAVO120 study design
INAVO120 study design1 N = 325 Efficacy endpoints Key eligibility criteria Inavolisib (9 mg QD PO) • PFS by investigator • Time from randomization to end or Enrichment of patients + palbociclib (125 mg PO • OS discontinuation of next-line treatment, or with poor prognosis: QD D1–D21) • ORR, BOR, CBR
Slide 5: INAVO120 primary analysis results
INAVO120 primary analysis results • INAVO120 (NCT04191499) is a Phase III, randomized, double-blind, placebo-controlled study that assessed inavolisib or placebo with palbociclib and fulvestrant in patients with PIK3CA-mutated, HR+, HER2– LA/mBC who recurred on or within 12 months of adjuvant endocr
Slide 6: Time to end of next-line treatment or death (PFS2 proxy)
Time from randomization to end or discontinuation of next-line treatment, or death from any cause (proxy for PFS2) 100 Inavo+Palbo+Fulv Pbo+Palbo+Fulv (n = 161) (n = 164) No. of events, n (%) 59 (36.6) 80 (48.4) 75 Median (95% CI), months 24.0 (18.6, NE) 15.1 (13.5, 22.3) Stratified hazard ratio (95
Slide 7: Time to first subsequent chemotherapy
Time from randomization to first subsequent chemotherapy after treatment discontinuation 100 Inavo+Palbo+Fulv Pbo+Palbo+Fulv (n = 161) (n = 164) No. of events, n (%) 48 (29.28) 68 (41.5) 75 Median (95% CI), months NE (24.8, NE) 15.0 (10.6, 24.8) Unstratified hazard ratio (95% CI) 0.54 (0.37, 0.78) E
Slide 8: Post-progression therapies
Post-progression therapies Inavo+Palbo+Fulv Pbo+Palbo+Fulv Patients, n/N (%) (n = 161) (n = 164) Discontinued treatment 93/161 (57.8) 115/164 (70.1) No subsequent therapy – death 12/161 (7.5) 19/164 (11.6) Received subsequent therapy* 65/161 (40.4) 82/164 (50.0) Chemotherapy (any) 40/65 (61.5) 60/82
Slide 9: Safety
Safety Key selected AEs Resolution of key selected AEs*† Pbo+Palbo+Fulv (n = 162) Inavo+Palbo+Fulv (n = 162) Pbo+Palbo+Fulv Inavo+Palbo+Fulv Hyperglycemia Diarrhea Rash Stomatitis/ mucosal inflammation 100 75 50 25 0 25 50 75 100 100 75 50 25 0 25 50 75 100 Patients (%) Patients (%) Grade 1–2 Grade
Slide 10: Time to onset of key selected AEs
Time to onset of key selected AEs* Hyperglycemia Rash Median (range), days: 7.0 (2.0–955.0) Median (range), days: 29.0 (1.0–952.0) Number of AEs/ 0.6 0.6 patients month 0.4 0.4 0.2 0.2 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 30 32 36 1 2 3 4 5 6 7 8 9 10 11 12
Slide 11: Inavolisib treatment interruption, reduction, and discontinuation due to key selected AEs
Inavolisib treatment interruption, reduction, and discontinuation due to key selected AEs Discontinuation rate of inavolisib due to any AE was 6.2%1 Stomatitis/ Patients, n (%) Hyperglycemia Diarrhea Rash mucosal inflammation Inavolisib interruption 44 (27.2) 11 (6.8) 2 (1.2) 16 (9.9) due to AE Inav
Slide 12: Concomitant medications for key selected AEs
Concomitant medications for key selected AEs Inavo+Palbo+Fulv Pbo+Palbo+Fulv Patients, n/N (%) (n = 162) (n = 162) Received ≥1 concomitant medication for: Hyperglycemia 66/162 (40.7) 1/162 (0.6) Diarrhea 46/162 (28.4) 6/162 (3.7) Rash 26/162 (16.0) 19/162 (11.7) Stomatitis/mucosal inflammation 69/16
Slide 13: Time to clinically meaningful deterioration in worst pain severity
Time to confirmed clinical meaningful deterioration in worst pain severity (BPI-SF) Patients in the inavolisib arm experienced a longer duration of time without confirmed, clinically meaningful worsening pain severity than patients in the placebo arm 100 Inavo+Palbo+Fulv Pbo+Palbo+Fulv (n = 161) (n
Slide 14: Symptomatic toxicities (PRO-CTCAE)
Symptomatic toxicities (PRO-CTCAE) • Most patients reported worst post-baseline symptomatic toxicities at moderate levels or less • Diarrhea, mouth sores, and rash were experienced at higher (worse) levels by patients in the inavolisib arm than the placebo arm 100 Baseline ≤mild/rarely/a little bit
Slide 15: Overall treatment bother
Overall “bother” Most patients reported overall “bother” from treatment as “not at all” or “a little bit” “In the last 7 days, how bothered were you by the side effect(s) of your treatment?” Inavo+Palbo+Fulv Pbo+Palbo+Fulv 100 Very much 100 Very much Quite a bit Quite a bit 75 Somewhat 75 Somewhat P
Slide 16: Mean change from baseline in EORTC QLQ-C30 scores
Mean change from baseline in EORTC QLQ-C30 scores HRQoL Physical functioning 20 20 Inavo+Palbo+Fulv Pbo+Palbo+Fulv Inavo+Palbo+Fulv Pbo+Palbo+Fulv 10 10 Mean change Mean change 0 0 –10 –10 Meaningful deterioration Meaningful deterioration –20 –20 Cycle 11 Day 1 Cycle 13 Day 1 Cycle 15 Day 1 Cycle 17
Slide 17: Conclusions
Conclusions • INAVO120 met its primary endpoint, with a statistically significant and clinically meaningful improvement in PFS (15.0 months versus 7.3 months; hazard ratio, 0.43 [95% CI = 0.32, 0.59]; p<0.0001)1 • Inavolisib with palbociclib and fulvestrant was associated with sustained benefit beyo
Slide 18: Lay summary
18 Lay summary What is the INAVO120 study?1 Key results from the INAVO120 study • INAVO120 is an ongoing Phase III study to test whether a study • Inavolisib + palbociclib + fulvestrant significantly increased the drug called inavolisib, combined with palbociclib + fulvestrant, average length of tim
Slide 19: Acknowledgments
Acknowledgments • We thank all the patients who participated in INAVO120, along with their families, as well as the INAVO120 investigators and research staff • This study was funded by F. Hoffmann-La Roche Ltd • Research support in the form of third-party writing assistance for this presentation, fu
Slide 20: Thank you
Thank you