NCT03886649

Copanlisib in Combination With Venetoclax in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma.

Copanlisib in Combination With Venetoclax in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma. A Multicenter Phase Ib Trial With Two Expansion Cohorts

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A significant number of patients with non-Hodgkin lymphoma (NHL) are not cured with available treatments and will eventually relapse. Those patients might not be able to tolerate more bone marrow toxicity, limiting their treatment options. Preclinical in vitro studies have demonstrated a synergism of venetoclax and copanlisib in different lymphomas. This may represent a safe and effective therapy for patients who relapsed or did not respond to standard therapy. The primary objective of this phase I trial is to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of copanlisib in combination with venetoclax in patients with relapsed or refractory B-cell NHL.

Detailed description

There are many different types of NHL. A lot of progress has been made over the last years in the management of NHL, and while some can be cured with available treatments, for others new treatments are necessary. A significant number of patients that cannot be cured with the available treatments will eventually relapse. Dysregulation of apoptosis via overexpression of the antiapoptotic BCL-2 protein is paramount for several subtypes of NHL. On the other hand, PI3K is a central pathway in the pathogenesis of lymphoma, and PI3K signaling is critical for the proliferation and survival of malignant cells such as follicular lymphoma (FL), marginal zone lymphoma (MZL), and others. The combination of copanlisib (PI3K inhibitor) and venetoclax (BLC-2 inhibitor) is interesting given their known single agent activity in B-cell NHL and their synergy observed in B-cell NHL preclinical models. The pharmacologic inhibition of PI3K by copanlisib has translated into significant clinical activity in different lymphoma subtypes. Venetoclax has proven successful in CLL and the first results in NHL are encouraging. Both compounds are currently in other combination studies in SLL/CLL and NHL but there are currently no clinical trials studying this particular combination. There is a need to further improve approaches in the relapsed/refractory setting of patients with NHL in need of systemic therapy and this combination may provide an opportunity for an active and well-tolerated regimen that does not present the short and long-term toxicities of chemotherapy. The phase Ib study here proposed will evaluate the safety, tolerability and preliminary antitumor activity of the novel combination of copanlisib with venetoclax, two drugs with single agent activity across different lymphoma subtypes in the dose escalation and in two small cohorts of patients with FL and MZL in the expansion phase.

Conditions

• Non-Hodgkin Lymphoma

Interventions

Type	Name	Description
DRUG	Copanlisib	Duration of IMP administration: a maximum of twelve 28-day cycles of the combination treatment. Copanlisib will be administered i.v. on days 1, 8, and 15 of each cycle. The only dose level 1 (DL1) is 60 mg copanlisib.
DRUG	Venetoclax	Duration of IMP administration: a maximum of twelve 28-day cycles of the combination treatment. Copanlisib will be administered i.v. on days 1, 8, and 15 of each cycle. The starting dose is dose level 1 (DL1): 600 mg venetoclax.

Timeline

• Start date: 2019-11-04
• Primary completion: 2021-05-10
• Completion: 2022-03-08
• First posted: 2019-03-22
• Last updated: 2022-04-01

Locations

6 sites across 1 country: Switzerland