RE:RE:RE:RE:RE:RE:RE:RE:RE:CG Oncology A Phase 1a/1b Study of ELVN-001 for the Treatment Chronic Myeloid
The purpose of this study is to evaluate the safety, tolerability and determine the recommended dose for further clinical evaluation.
Study Start (Actual)
2022-05-22
Primary Completion (Estimated)
2026-12
Study Completion (Estimated)
2026-12
Enrollment (Estimated) 120 patients
Cohort 1 10/20mg- n=20 patients
Cohort 2 40/80mg- n=20 patients
Cohort 3 80/120mg - n=20 patients
Up to an additional 30 patients may be enrolled at any dose level
that has cleared the 28-day dose limiting toxicity (DLT) window.
ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer (HER2)
Brief Summary:
The goal of this clinical trial is to test ELVN-002 in people with cancers that have an abnormal HER2 gene. The main question the trial aims to answer is if ELVN-002 is safe and tolerable at different doses.
There are 4 parts to the trial. Part 1 is a dose escalation with ELVN-002 monotherapy for people with advanced stage solid tumors that have a HER2 mutation, amplification or high HER2 over-expression. Part 2 is an ELVN-002 monotherapy dose exploration where additional people may be enrolled at dose levels that have cleared the dose escalation in Part 1 to further evaluate the safety, tolerability, pharmacokinetics and clinical activity. Part 3 is a dose expansion of ELVN-002 monotherapy which will enroll up to 40 patients people with advanced stage HER2 mutant non-small cell lung cancer. Patients in Part 3 will be randomized 1:1 to receive one of two dose levels.
Part 4 is a combination dose escalation where, based on the results of Part 1 and 2, a combination of ELVN-002 and either fam-trastuzumab deruxtecan-nxki (in HER2 mutant non-small cell lung cancer) or trastuzumab emtansine (in HER2 positive breast cancer) will be evaluated for safety and tolerability.
Phase 1a Monotherapy Dose Exploration
ELVN-002 will be administered either once or twice daily
A maximum of 60 patients will enroll in this arm. A maximum of 10 patients may be enrolled at a single dose or tumor type.
Experimental: Phase 1b Monotherapy Dose Expansion
ELVN-002 will be administered either once or twice daily. A maximum of 40 patients will enroll in this arm
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Background: Oncolytic viruses are promising cancer immunotherapies but questions have been raised regarding their safety. Pelareorep (REOLYSIN, R), an unmodified Reovirus Dearing strain, selectively replicates and lyses cancer cells and induces anti-tumor immunity. To date, 900+ patients (pts) have been treated with intravenous (IV) pelareorep. In a phase 2 trial, its combination with paclitaxel improved overall survival (17.4m) vs paclitaxel (10.4m) in metastatic breast cancer (MBC) pts (HR 0.65, 80% CI 0.46-0.91, p = 0.1; Berstein et.al. AACR2017). A pooled analysis was thus conducted to better characterize pelareorep’s safety profile in combinations with paclitaxel.
Methods: 1417 patients have been enrolled in 36 trials: 934 patients received IV pelareorep and 359 were in control arms. Data from 8 trials with paclitaxel (P), paclitaxel + pelareorep (PR), carboplatin + paclitaxel (CP) or carboplatin + paclitaxel + pelareorep (CPR) were pooled. Standard doses of P (weekly) and CP were administered. Pelareorep IV dose was 3x1010 TCID50 (5-6 doses q21-28 d). Various advanced solid tumors were evaluated, including the 81 patients with MBC.
Conclusions: This is the largest database reported to date examining the safety of an IV viral agent. Pelareorep’s administration, in combination with paclitaxel or carboplatin-paclitaxel, is safe and well tolerated.
Ref: Annals of oncology