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Displaying One Session

Proffered Paper session
Date
Mon, 20.09.2021
Time
13:30 - 14:40
Location
Channel 3
Proffered Paper session

825O - Ivosidenib in Chinese patients (pts) with relapsed/refractory acute myeloid leukemia (R/R AML) with an IDH1 mutation: Results from a bridging registrational study

Presentation Number
825O
Speakers
  • Mingyuan Sun (Tianjin, China)
Lecture Time
13:30 - 13:40
Location
Channel 3, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:40

Abstract

Background

Mutations in IDH1 occur in 6–10% of pts with AML and are associated with a poor prognosis. Ivosidenib is a first-in-class, potent, oral, targeted, small-molecule inhibitor of mutant IDH1 (mIDH1), which has been approved by the US FDA to treat mIDH1 R/R AML based on the clinical efficacy results from the global pivotal AG120-C-001 study. In China, however, there is still no standard of care therapy for this rare pt population. Here we report for the first time the clinical data from the bridging registrational study of ivosidenib in Chinese pts with mIDH1 R/R AML.

Methods

Adult R/R AML pts with a central lab–confirmed IDH1 R132 mutation were eligible. Ivosidenib was dosed orally at 500 mg once daily in 28-day cycles. The primary endpoint was pharmacokinetics (PK). Key secondary endpoints included safety and efficacy, with a primary efficacy endpoint of complete remission (CR) + CR with partial hematologic recovery (CRh) rate.

Results

As of 18 Jan 2021, 30 pts were treated, with 17 remaining on treatment. In the prespecified 9 PK-evaluable pts, the Cmax (4730 ng/mL) was reached 3.98 h after single-dose administration and AUC0-24 was 62100 ng*h/mL. Systemic exposure parameters demonstrated moderate to high variability. The CR+CRh rate was 30.0% (9/30; 95% CI: 14.7–49.4%), with all 9 pts achieving CR. Median duration of CR+CRh was not reached (range: 0.03–10.09mos) and median time to CR+CRh was 2.79 mos (range: 1.0–6.5). Objective response rate was 36.7% (11/30; 95% CI: 19.9–56.1%). One (3.3%) pt received hematopoietic stem cell transplantation after achieving CR. Transfusion independence was achieved in 7/18 pts (38.9%) and maintained in 8/12 pts (66.7%). All pts reported treatment-emergent adverse events (TEAEs). Grade ≥3 TEAEs occurred in 26 (86.7%) pts, most commonly platelet count decreased (36.7%), neutrophil count decreased (33.3%) and anemia (33.3%). Two fatal TEAEs occurred in 2 (6.7%) pts, with neither related to ivosidenib. Serious AEs were reported in 18 (60.0%) pts.

Conclusions

Ivosidenib was well tolerated and induced durable remissions with clinical benefits in Chinese pts with mIDH1 R/R AML, potentially fulfilling an unmet medical need for this rare pt population in China.

Clinical trial identification

NCT04176393.

Legal entity responsible for the study

CStone Pharmaceuticals.

Funding

CStone Pharmaceuticals.

Disclosure

Y. Zhang, R. Chen, Z. Shen, X. Yu, K. Liu: Financial interests, Personal, Full or part-time Employment: CStone Pharmaceuticals. J. Yang: Financial Interests, Personal, Officer: CStone Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals. Financial interests, Personal, Full or part-time Employment: CStone Pharmaceuticals. All other authors have declared no conflicts of interest.

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Proffered Paper session

Invited Discussant 825O

Speakers
  • Markus G. Manz (Zurich, Switzerland)
Lecture Time
13:40 - 13:50
Location
Channel 3, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:40
Proffered Paper session

Q&A and live discussion

Lecture Time
13:50 - 14:00
Location
Channel 3, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:40
Proffered Paper session

826O - Copanlisib plus rituximab vs placebo plus rituximab in patients (pts) with relapsed marginal zone lymphoma (MZL) treated in the phase III CHRONOS-3 trial

Presentation Number
826O
Speakers
  • Muhit Özcan (Ankara, Turkey)
Lecture Time
14:00 - 14:10
Location
Channel 3, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:40

Abstract

Background

The randomized, double-blind, placebo-controlled phase III CHRONOS-3 study (NCT02367040) showed a 48% risk reduction in disease progression/death with the PI3K inhibitor copanlisib + rituximab (C+R) vs placebo (P)+R in pts with relapsed indolent non-Hodgkin lymphoma (iNHL). We report a subset analysis in pts with MZL.

Methods

Pts with relapsed iNHL progression- and treatment-free for ≥12 months (mo) after R-based therapy or ≥6 mo if unwilling/unfit to receive chemotherapy were randomized 2:1 to C+R or P+R. C 60 mg/P was given i.v. on days (d) 1, 8, and 15 (28-d cycle); R 375 mg/m2 was given i.v. on d 1, 8, 15, and 22 of cycle 1 and d 1 of cycles 3, 5, 7, and 9. Primary endpoint was centrally assessed progression-free survival (PFS).

Results

Of 458 pts in CHRONOS-3, 66 with MZL were randomized to C+R and 29 to P+R. MZL subtypes included nodal (39%), extranodal (37%), and splenic (24%). With a median follow-up of 18.0 mo, C+R significantly reduced the risk of disease progression/death vs P+R; objective response rate (ORR) improved with C+R (Table). Median duration of response was 25.4 mo for C+R vs 9.3 mo for P+R; median time to progression was 33.2 mo vs 11.5 mo. Median overall survival was not evaluable (NE). Most common treatment-emergent adverse events (TEAEs; all grade/grade 3+) with C+R were hyperglycemia (65%/54%) and hypertension (54%/45%). Most common TEAEs with P+R were hyperglycemia (24%/10%), cough (24%/0%) and upper respiratory tract infection (24%/0%). Serious TEAEs were higher with C+R (57%) vs P+R (28%). TEAEs deemed related to C/P included hyperglycemia (63%/24%) and hypertension (54%/17%).

Treatment Overall MZL Nodal MZL Extranodal MZL Splenic MZL
C+R P+R C+R P+R C+R P+R C+R P+R
N 66 29 25 12 24 11 17 6
Median PFS, months (95% CI) 22.1 (13.8, NE) 11.5 (5.6, 16.3) 21.5 (13.1, NE) 11.5 (2.5, NE) NE (9.0, NE) 10.8 (1.6, 35.6) Not reliably estimable
HR (95% CI) C+R vs P+R 0.475 (0.245, 0.923) 0.483 (0.183, 1.276) 0.334 (0.111, 1.010)
1-sided p value 0.012 0.067 0.021
ORR, % ( n ) 75.8 (50) 41.4 (12) 88.0 (22) 33.3 (4) 75.0 (18) 45.5 (5) 58.8 (10) 50.0 (3)
Complete response rate, % ( n ) 39.4 (26) 10.3 (3) 32.0 (8) 8.3 (1) 58.3 (14) 9.1 (1) 23.5 (4) 16.7 (1)

Primary efficacy evaluation for PFS based on unstratified log-rank test and unstratified Cox proportional hazard model

Conclusions

C+R showed superior efficacy vs P+R in pts with relapsed MZL, including nodal MZL. The safety profile of C+R was consistent with C and R as monotherapy. Copanlisib is the first PI3K inhibitor to be safely combined with R in a phase III setting in pts with relapsed MZL and represents a new therapeutic strategy.

Clinical trial identification

NCT02367040.

Editorial acknowledgement

Writing support by Ryan Staudt, PhD, Complete HealthVizion.

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Disclosure

M. Özcan: Financial Interests, Personal, Other, Honoraria: Amgen; Non-Financial Interests, Personal, Other, Travel support: Amgen; Non-Financial Interests, Personal, Other, Travel support: Bristol Myers Squibb; Financial Interests, Personal, Other, Financial relationships: Abdi İbrahim; Financial Interests, Personal, Other, Financial relationships: Jazz Pharmaceuticals; Financial Interests, Personal, Other, Financial relationships: Sanofi; Financial Interests, Personal, Research Grant: AbbVie; Non-Financial Interests, Personal, Other, Travel support: AbbVie; Financial Interests, Personal, Research Grant: Archigen Biotech; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Other, Travel support: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Other, Travel support: Janssen; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Takeda. P. Panayiotidis: Financial Interests, Personal, Other, Honoraria: Genesis; Financial Interests, Personal, Other, Honoraria: Gilead; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Research Grant: Genesis; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Takeda. L. Mongay Soler: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc. A. Cao: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc. F. Hiemeyer: Financial Interests, Personal, Full or part-time Employment: Bayer AG. B.H. Childs: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc. M.J. Matasar: Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Other, Consultancy, honoraria: Bayer; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo; Financial Interests, Personal, Research Grant: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Consultancy, honoraria: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Consultancy: Juno Therapeutics; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal, Research Grant: Rocket Medical; Financial Interests, Personal, Other, Consultancy: Rocket Medical; Financial Interests, Personal, Research Grant: Seattle Genetics; Financial Interests, Personal, Other, Consultancy, honoraria: Seattle Genetics; Financial Interests, Personal, Other, Consultancy, honoraria: Takeda; Financial Interests, Personal, Other, Consultancy: Teva; Financial Interests, Personal, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Research Grant: ImmunoVaccine Technologies; Financial Interests, Personal, Other, Honoraria: ImmunoVaccine Technologies; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Research Grant: Pharmacyclics; Financial Interests, Personal, Other, Honoraria: Pharmacyclics. P.L. Zinzani: Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Gilead; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Incyte; Financial Interests, Personal, Other, Honoraria, speakers’ bureau involvement, consultancy: Janssen; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Kyowa Kirin; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Merck; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement, consultancy: MSD; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Roche; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Servier; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Takeda; Financial Interests, Personal, Other, Honoraria, speakers’ bureau involvement: TG Therapeutics; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement, consultancy: Verastem; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: ADC Therapeutics; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Celgene; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Celltrion; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Immune Design; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Janssen-Cilag; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Portola; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Sandoz; Financial Interests, Personal, Other, Consultancy: Sanofi. All other authors have declared no conflicts of interest.

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Proffered Paper session

833O - A phase Ib study result of HMPL-689, a PI3Kδ inhibitor, in Chinese patients with relapsed/refractory lymphoma

Presentation Number
833O
Speakers
  • Junning Cao (shanghai, China)
Lecture Time
14:10 - 14:20
Location
Channel 3, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:40

Abstract

Background

HMPL-689, a novel class I PI3Kδ inhibitor, has shown tolerable safety profile and encouraging preliminary efficacy in patients (pts) with relapsed/refractory (R/R) lymphoma in the dose-escalation stage of a phase I study (NCT03128164) in China (Junning C, et al, ASH 2020). Here we present the preliminary safety and efficacy results of the study evaluating HMPL-689 at recommended phase 2 dose (RP2D) of 30mg QD as a monotherapy in pts with R/R lymphomas.

Methods

Eligible pts had measurable R/R lymphoma who failed an anti-CD20 antibody (monotherapy or in combination) or systemic therapy. Patients received single agent HMPL-689 30mg QD continuously in sequential 28-day treatment cycles until progression, unacceptable toxicity, or death. The primary efficacy endpoint is investigator assessed objective response rate (ORR) using the International Working Group criteria (2008) and Lugano response criteria.

Results

As of March 30, 2021, a total of 75 pts had received at least one dose of HMPL-689 at RP2D, including 2 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/ SLL), 21 follicular lymphoma (FL), 14 marginal zone lymphoma (MZL), 7 mantle cell lymphoma (MCL) and 31 diffuse large B-cell lymphoma (DLBCL). The median age was 56 years (range 18 - 86 yrs). The median number of prior therapies was 2 (range 1- 8), and 41.3% of pts received ≥3 lines of therapy. The median follow up of all pts was 4.0 months (95% CI, 3.7- 5.5). Among the 60 pts who had at least one post-baseline tumor assessment, 8 pts achieved a complete response (CR), including 7 FL and 1 MCL and 23 partial responses. The ORR was 51.7% (31/60), the median time to response (TTR) was 1.9 months (95%CI, 1.8-1.9). Patients with FL demonstrated the ORR of 77.8% (14/18) and CR rate of 38.9% (7/18). The most common (≥ 10%) treatment emergent adverse events (TEAEs) were neutropenia, ALT increased, leukopenia, AST increased, hypertriglyceridemia, pneumonia and upper respiratory tract infection. The most common TEAEs of Grade ≥3 (≥10%) were neutropenia, pneumonia and rash.

Conclusions

HMPL-689 showed tolerable safety profile and promising single-agent clinical activity in pts with R/R B-cell lymphoma, with high ORR and CR rates noted particularly for FL patients.

Clinical trial identification

NCT03128164.

Legal entity responsible for the study

Hutchison MediPharma Limited.

Funding

Hutchison MediPharma Limited.

Disclosure

X. Duan, S. Fan, Y. Cai, W. Su: Financial Interests, Institutional, Sponsor/Funding Hutchison Medi. Pharma. All other authors have declared no conflicts of interest.

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Proffered Paper session

Invited Discussant 826O and 827O

Speakers
  • Lena Specht (Copenhagen, Denmark)
Lecture Time
14:20 - 14:30
Location
Channel 3, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:40
Proffered Paper session

Q&A and live discussion

Lecture Time
14:30 - 14:40
Location
Channel 3, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:40