senaparib (IMP4297)

P2, N=18, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P1/2, N=59, Completed, Impact Therapeutics, Inc. | Recruiting --> Completed | N=113 --> 59 | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Oct 2024 --> Apr 2024

P1/2, N=4, Terminated, Shanghai Jun Pai Ying Shi Therapeutics Co., Ltd. | N=57 --> 4 | Trial completion date: Jul 2024 --> Sep 2023 | Recruiting --> Terminated | Trial primary completion date: Jul 2024 --> Sep 2023; The sponsor voluntarily requested termination

P1, N=61, Recruiting, Impact Therapeutics, Inc. | Phase classification: P1/2 --> P1

In combination studies, Senaparib used with temozolomide (TMZ) had shown strong synergistic cytotoxicity in both in vitro and in vivo experiments. Senaparib represents a novel class of PARP1 inhibitors that can be used for the treatment of cancer. A phase III clinical study of Senaparib for maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer has met its primary endpoint, and a new drug application of Senaparib has been accepted by National Medical Products Administration (NMPA) of China for review.

These results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 .

No new safety signals were identified among all subgroups. Conclusion/Implications Maintenance senaparib significantly improved PFS regardless of FIGO stage, 1L treatment response, surgical timing and residual disease status versus placebo in patients with newly diagnosed advanced OC.

The most common grade â¥3 TEAEs were anemia (x%) , thrombocytopenia (x%), and neutropenia (x%).Conclusion Pts who received Sena had a meaningful and significant improvement in PFS compared to those who received PBO and the PFS is much longer than other PARP inhibitors, regardless of biomarker status. Sena was well tolerated, no new safety signals were identified.

As of 30 Jan 2023, 93 pts were enrolled. 59%/41% pts were partially/fully platinum sensitive. Median lines of prior systemic chemotherapy(CT) was 2 (range 2-7), and 71%/29% received 2 / ≥ 3 lines of CT.

Conclusions Senaparib demonstrated clinically meaningful antitumor activity and manageable safety profile in BRCA1/2 mutated recurrent PSOC. The OS was immature but seemed to be improved.

Table: LBA36 Senaparib (n=271), m Placebo (n=133), m HR (95%CI), P value PFS (BICR) NR 13.6 0.43 (0.32-0.58) P < 0.0001 PFS (BICR) BRCA + NR 15.6 0.43 (0.24-0.76) P = 0.0026 PFS (BICR) BRCA- NR 12.9 0.43 (0.30-0.61) P < 0.0001 PFS (INVR) NR 11.1 0.43 (0.32-0.57) P < 0.0001 PFS (INVR) BRCA + NR 11.1 0.33 (0.20-0.56) P < 0.0001 PFS (INVR) BRCA- NR 11.1 0.48 (0.34-0.67) P < 0.0001 TFST NR 14.4 0.44 (0.33-0.59) P < 0.0001 BICR, blinded independent central review; INVR, investigator review; HR, hazard ratio; NR, not reached; PFS, progression-free survival; BRCA +, breast cancer susceptibility gene (BRCA) mutation positive; BRCA -, BRCA mutation negative; TFST, time to first subsequent therapy or death; m, month Conclusions 1L maintenance Senaparib led to an unprecedented reduction in the risk of progression or death versus placebo in OC, regardless of biomarker status. Senaparib was well tolerated, no new safety signals were identified.

Clinical survival benefit was observed for the combination of continuous senaparib with intermittent low-dose temozolomide (D1-21 of a 28-day cycle) in relapsed ES-SCLC patients with quick tumour shrinkage during the first 2 cycles. The most common TEAE (haematological toxicity) could be well managed. The relationship between homogeneous recombination repair gene mutations, e.g., FANC family and the combination in ES-SCLC patients warrants further research.

Senaparib was well tolerated and demonstrated promising antitumor activity in Chinese patients with advanced solid tumors. The RP2D for this clinical study in China was identified as 100 mg QD.

Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily.

P1, N=0, Withdrawn, Shanghai Junshi Bioscience Co., Ltd. | N=118 --> 0 | Not yet recruiting --> Withdrawn

No abstract available

Several clinical combination studies of PARP inhibitors with TMZ have been reported, such as the combination of olaparib with TMZ in small cell lung cancer (SCLC). In vivo studies of high-dose senaparib in combination with low-dose TMZ once a day continuously in human SCLC NCI-H209 xenograft model was found to be highly synergetic and well tolerated. A clinical study of senaparib in combination with TMZ in patients with advanced solid tumors and SCLC is ongoing

Several PARP inhibitors, including olaparib, rucaparib, niraparib, talazoparib, fluzoparib and pamiparib have been approved for the treatment of several types of cancer. Senaparib is currently in several phase I/II, phase II and phase III clinical studies for the treatment of multiple tumor types either as single agent or in combination with temozolomide (TMZ). The most advanced study of senaparib is a phase III study as maintenance therapy in platinum-sensitive advanced ovarian cancer patients following first-line chemotherapy

P1, N=118, Not yet recruiting, Shanghai Junshi Bioscience Co., Ltd.

P2, N=165, Ongoing, IMPACT Therapeutics, Inc.

P1, N=39, Completed, Impact Therapeutics, Inc. | Active, not recruiting --> Completed

P1, N=57, Completed, Impact Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Jun 2021 --> Dec 2020

P1, N=57, Active, not recruiting, Impact Therapeutics, Inc. | Trial completion date: Dec 2020 --> Jun 2021

P1, N=39, Active, not recruiting, Impact Therapeutics, Inc. | Trial completion date: Dec 2021 --> Mar 2021 | Trial primary completion date: Dec 2020 --> Sep 2020

P1, N=57, Active, not recruiting, Impact Therapeutics, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Oct 2021 --> Dec 2020 | Trial primary completion date: Apr 2021 --> Dec 2020

Background Seneparib (previously known as IMP4297) is a novel oral PARP inhibitor which is 20-fold more potent than olaparib in vivo and showing strong antitumor activity in preclinical studies. Funding: IMPACT Therapeutics Inc. Clinical trial identification: NCT03508011.

Legal entity responsible for the study: IMPACT Therapeutics Inc. Funding: IMPACT Therapeutics Inc.

P1, N=60, Recruiting, Impact Therapeutics, Inc. | N=30 --> 60 | Trial completion date: Oct 2020 --> Oct 2021 | Trial primary completion date: Oct 2019 --> Apr 2021

P1, N=39, Active, not recruiting, Impact Therapeutics, Inc. | Recruiting --> Active, not recruiting | N=30 --> 39 | Trial primary completion date: Jul 2020 --> Dec 2020

P3, N=393, Recruiting, Impact Therapeutics, Inc. | Not yet recruiting --> Recruiting