Phase I Study of SYD985 With Niraparib in Patients With Solid Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04235101|
Recruitment Status : Recruiting
First Posted : January 21, 2020
Last Update Posted : June 26, 2020
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor||Drug: SYD985 + Niraparib||Phase 1|
This is an open-label, single-arm study in which patients with HER2-expressing locally advanced or metastatic solid tumours will be treated with both an anti-body drug conjugate SYD985 and a Poly (ADP-ribose) Polymerase (PARP) inhibitor niraparib. SYD985 is an antibody-drug conjugate and consists of two parts. The antibody part binds to a protein that exists on different types of cancer cells (HER2 protein). When SYD985 binds to this protein, it will be taken up by the cancer cell. The second part of the drug, a toxin, will be cleaved in the cell and subsequently kills the cancer cell. Niraparib blocks the action of enzymes PARP-1 and PARP-2, which help to repair damaged DNA in cells when the cells divide to make new cells. By blocking PARP enzymes, the damaged DNA in cancer cells cannot be repaired, and, as a result, the cancer cells die.
Part 1 includes patients with locally advanced or metastatic HER2-expressing solid tumours of any origin that showed progression on standard therapy or for whom no standard therapy exists. Patients will receive SYD985 infusions every three weeks in combination with niraparib until progression of the cancer or unacceptable toxicity develops. In this first part of the study, different doses of niraparib will be given for either 1, 2 or 3 weeks.
Part 2 includes patients with advanced or metastatic breast, ovarian or endometrial cancer that showed progression on standard therapy or for whom no standard therapy exists. Patients will receive SYD985 infusions every three weeks in combination with niraparib until progression of the cancer or unacceptable toxicity develops.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors.|
|Actual Study Start Date :||June 22, 2020|
|Estimated Primary Completion Date :||July 2022|
|Estimated Study Completion Date :||December 2022|
Experimental: SYD985 + Niraparib
SYD985, Intravenous, every 3 weeks (Q3W) Niraparib taken orally and either 100 mg, 200 mg or 300 mg once daily for either 1, 2 or 3 weeks.
Drug: SYD985 + Niraparib
SYD985 powder for concentrate for solution for infusion Niraparib 100 mg per hard capsule
Other Name: (vic-)trastuzumab duocarmazine + Zejula
- Incidence of dose-limiting toxicities [ Time Frame: 21 days ]First cycle
- Number of patients with adverse events [ Time Frame: up to 2 years ]
- Area under the plasma concentration versus time curve (AUC) of SYD985 and niraparib [ Time Frame: Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months ]
- Peak plasma concentration of SYD985 and niraparib [ Time Frame: Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months ]
- Change from baseline in hematology and blood chemistry parameters [ Time Frame: Baseline and every cycle up to 2 years ]
- Number of patients with antibodies against SYD985 [ Time Frame: Baseline and every cycle up to 2 years ]
- Objective response rate [ Time Frame: Baseline and every two cycles for up to 6 months, subsequent every 4 cycles up to 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04235101
|Contact: Norbert Koper||+31 (0)24 679 email@example.com|
|University Hospital Antwerp, BE||Recruiting|
|Antwerp, Belgium, 2650|
|Institut Jules Bordet||Recruiting|
|Brussel, Belgium, 1000|
|The Royal Marsden NHS Foundation Trust||Recruiting|
|London, United Kingdom, SM2 5PT|
|Study Director:||Norbert Koper||Byondis B.V., The Netherlands|