Itari (linperlisib)

P1, N=33, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

Linperlisib showed an acceptable safety profile and preliminary clinical benefit in patients with a range of advanced solid tumors. Further studies of linperlisib safety and efficacy are warranted.

Linperlisib treatment for these patients with r/r PTCL, consisting of the major PTCL subtypes, was observed to have a 60.5% overall response rate with 35% complete responses and led to a median duration of response of 11.1 months, median progression-free survival of 11.8 months, and a median overall survival of >38 months (not reached). With the very promising clinical activity against r/r PTCL, the results of this study support the further investigation of linperlisib for the treatment of r/r PTCL.

P1/2, N=131, Not yet recruiting, The First Affiliated Hospital,Zhejiang University School of Medicine; The First Affiliated Hospital,Zhejiang University School of Medicine

P1/2, N=35, Recruiting, The First Hospital of Jilin University

P2/3, N=606, Not yet recruiting, Shanghai YingLi Pharmaceutical Co. Ltd.

P=N/A, N=89, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.; Institute of Hematology & Bloo

P2, N=89, Recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1, N=43, Completed, Shanghai YingLi Pharmaceutical Co. Ltd. | Unknown status --> Completed | Phase classification: P1b --> P1 | N=80 --> 43

P1, N=8, Completed, Institute of Hematology & Blood Diseases Hospital, China | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Feb 2024 | Trial primary completion date: Dec 2024 --> Jan 2024

P1/2, N=43, Recruiting, Beijing Tongren Hospital

P4, N=88, Not yet recruiting, Shanghai YingLi Pharmaceutical Co. Ltd.

P2, N=10, Not yet recruiting, Dalian Medical University

P1, N=4, Terminated, Institute of Hematology & Blood Diseases Hospital, China | N=20 --> 4 | Trial completion date: Dec 2024 --> Feb 2024 | Recruiting --> Terminated; Did not meet the anticipated outcome.

P2, N=41, Recruiting, Institute of Hematology & Blood Diseases Hospital, China

P2, N=33, Recruiting, The First Affiliated Hospital of Xiamen University

P1, N=8, Active, not recruiting, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Active, not recruiting

Although minor differences were observed in this subgroup, their significance is limited due to the small sample sizes and probably do not alter the overall clinical benefit of linperlisib. Nevertheless, these findings warrant further investigation.

Our post-hoc analysis reveals that elderly patients (≥60 years old) have reduced tolerance to linperlisib, necessitating more frequent dose adjustments due to AEs. Notably, treatment discontinuation results in inferior DOR and PFS, while dose adjustments or suspensions yield comparable DOR and PFS to full-dose treatment, suggesting that tolerability-guided dose modification effectively reduces AEs without sacrificing therapeutic efficacy.

P1/2, N=48, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

P1/2, N=32, Recruiting, Peking Union Medical College Hospital

Patient-derived HR + ABC xenografts were implanted into immune-humanized NSG mice and subsequently treated with YY20394 (PI3Kδ inhibitor) and camrelizumab. Mechanistically, YY20394 only effectively inhibited the PI3K pathway and proliferation activity in Tregs but not in BCCs. Our study suggests PI3Kδ inhibitor could the enhance the efficacy of ICIs in HR + BC PDX models by combating immune suppression and provides a feasible approach that may overcome the resistance of ICIs in HR + BC patients.

P1/2, N=48, Not yet recruiting, Sun Yat-sen University

Do we require an autologous stem cell transplantation in all patients? Is there room for improvement in the setting of relapsed and refractory disease?

P=N/A, N=1000, Not yet recruiting, Ruijin Hospital

For elderly patients, linperlisib also showed promising efficacy, which was similar to the results in younger patients. Infectious pneumonia needs attention in elderly patients, but the overall safety profile is manageable. Follicular lymphoma, Phase II, PI3K

The efficacy of linperlisib was numerically better in patients with relapsed follicular lymphoma than those with refractory follicular lymphoma. Grade ≥3 interstitial lung disease was relatively more common in patients with refractory follicular lymphoma. PI3K, Follicular lymphoma, Phase II

Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory FL patients who had received at least two prior systemic therapies.

P2, N=97, Recruiting, Shanghai YingLi Pharmaceutical Co. Ltd. | Not yet recruiting --> Recruiting

The major metabolic pathways involved N-dealkylation, O-dealkylation, glucuronidation and acetylation.4. Overall, renal elimination played a significant role in the disposition of YY-20394, and the morphine ring and side chain of the piperidine ring were the predominant metabolic sites.

AEs that were potentially immune-mediated, such as diarrhea, colitis, pneumonitis, and transaminitis, were observed at significantly lower incidences of occurrence. Conclusion Linperlisib demonstrated compelling clinical efficacy and a promising safety profile, which has the potential to surpass the approved PI3K inhibitors for the treatment of relapsed or refractory FL patients after two prior therapies.

P2, N=97, Not yet recruiting, Shanghai YingLi Pharmaceutical Co. Ltd.

Furthermore, linperlisib showed a favorable safety profile with respect to the previously reported information from approved agents in the class of PI3K inhibitors. Further clinical studies of linperlisib in B-cell malignancies and in combination therapies are warranted.

The gemcitabine (GEM) oxaliplatin (OX) chemotherapy regimen is a standard treatment option with modest side effects providing an opportunity for potential combination with novel agents...Most pts (74%,29pts) had received R-CHOP as a first line treatment, with later lines of R-EPOCH, R-ICE, lenolinamide, CAR-T, PD-1, and other regimens, with a median of 2 lines of prior systemic therapy...A Phase2 study of linperlisib in combination with GEMOX in r/r DLBCL is currently ongoing. Further, multiple combination treatments are planned as important avenues for future development of linperlisib.

Conclusions The PI3Kd-selective oral agent, linperlisib, demonstrated promising efficacy and durable responses with a 61.0% ORR and 10.3 months median PFS in patients with r/r PTCL. Additional clinical studies of linperlisib in r/r PTCL, including a Phase 2 registration study, are currently ongoing.

A recommended phase 2 dose of 80 mg q.d. was established. Considering that YY-20394 was well-tolerated with promising preliminary efficacy, further development is warranted.Trial registration clinicaltrials.gov, NCT03757000, retrospectively registered, November 28, 2018, https://clinicaltrials.gov/ct2/show/NCT03757000?term=NCT03757000&draw=2&rank=1 .

P2, N=102, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.