elvn-002 with trastuzumab +/- chemotherapy in her2+ solid tumors, colorectal and breast cancer

Conditions: HER2-positive Breast Cancer; HER2-positive Gastric Cancer; HER2 Positive Solid Tumors; HER2 Amplification; Colorectal Cancer

Summary: the purpose of this study is to determine the safety, tolerability, and recommended dose of elvn-002 in combination with trastuzumab in participants with advanced-stage her2-positive tumors and in combination with trastuzumab, and chemotherapy in participants with advanced-stage her2-positive colorectal cancer and breast cancer.

parts 1 and 3 of this study are designed to evaluate preliminary safety, tolerability, and pharmacokinetics (pk) of elvn-002 in combination with trastuzumab in participants with advanced stage her2 positive solid tumors. in addition, part 3 will evaluate the preliminary efficacy of elvn-002 in combination with trastuzumab in participants with advanced-stage her2-positive solid tumors. part 2 of this study will evaluate the preliminary safety, tolerability, and pk of elvn-002 in combination with trastuzumab and chemotherapy; capecitabine and oxaliplatin(capeox) or 5-fluorouracil (5-fu), leucovorin (lcv) and oxaliplatin (mfolfox6) in participants with advanced stage her2 positive colorectal cancer, or eribulin or capecitabine in participants with advanced-stage her2-positive breast cancer, or paclitaxel in participants with advanced stage solid tumors. in part 4, the preliminary safety, tolerability, pk, and efficacy of elvn-002 in combination with trastuzumab and capeox or mfolfox6 will be evaluated in participants with her2-positive colorectal cancer.

Eligibility criteria:
inclusion criteria: * pathologically or histologically documented solid tumor. * locally advanced or relapsed/refractory disease or unresectable metastatic disease. * her2-positive disease based on the following local testing: * colorectal cancer: ihc3+, ihc2+/ish+, ngs amplification by tissue (no ras or braf mutation allowed) * breast cancer: ihc3+ or ihc2+/ish+ by tissue * gastric cancer: ihc3+ or ihc2+/ish+ by tissue * other cancers: ihc3+, ihc2+/ish+, ngs amplification by tissue or ctdna * prior therapies for part 1 (dose escalation elvn-002 + trastuzumab): * colorectal cancer: treated with prior fluoropyrimidine, oxaliplatin, irinotecan-based regimens, anti-epidermal growth factor receptor (egfr) treatment (if clinically indicated), anti-vascular endothelial growth factor (vegf) treatment (if clinically indicated), and an anti-programmed death ligand 1 (pd-(l)-1) treatment (if the tumor is microsatellite instability (msi)-high/deficient mismatch repair (dmmr) * breast cancer: treated with prior taxane, pertuzumab, trastuzumab, and fam-trastuzumab deruxtecan (t-dxd) if available and appropriate based on local standard of care and investigator's assessment * gastric cancer: treated with trastuzumab/platinum fluorouracil containing regimen and t-dxd. * other cancers: progressed during or after ≥ 1 prior line of systemic therapy for locally advanced unresectable or metastatic disease * prior her2 targeted therapy is allowed * prior therapies for part 2 (phase 1a dose escalation elvn-002 + trastuzumab + chemotherapy): * colorectal cancer: candidate for capeox (capecitabine and oxaliplatin) or mfolfox6 (5-fu, lcv and oxaliplatin), and treated, if clinically indicated, with an anti-programmed death ligand 1 (pd-(l)-1) treatment (if the tumor is microsatellite instability (msi)-high/deficient mismatch repair (dmmr). prior her2 targeted therapy is allowed. * breast cancer: candidate for capecitabine, paclitaxel or eribulin, and treated with prior taxane, pertuzumab, trastuzumab, and t-dxd, if available and appropriate, based on local standard of care and investigator's assessment. no prior her2 targeted tyrosine kinase inhibitor therapy (antibody-drug conjugates and antibodies are allowed), no prior capecitabine (for the capecitabine cohort), no prior eribulin (for the eribulin cohort), and no taxane as immediate prior therapy (paclitaxel cohort). * prior therapies for part 3 (phase 1b dose expansion elvn-002 + trastuzumab): * colorectal cancer: treated with prior fluoropyrimidine, oxaliplatin, irinotecan-based regimens, anti-epidermal growth factor receptor (egfr) treatment (if clinically indicated), anti-vascular endothelial growth factor (vegf) treatment (if clinically indicated), and an anti-programmed death ligand 1 (pd-(l)-1) treatment if the tumor is microsatellite instability (msi)-high/deficient mismatch repair (dmmr). no prior her2 targeted therapy. * breast cancer: treated with prior taxane, pertuzumab, trastuzumab, and t-dxd if available and appropriate based on local standard of care and investigator's assessment. no prior her2 targeted tyrosine kinase inhibitor therapy (antibody-drug conjugates and antibodies are allowed). * gastric cancer: treated with prior trastuzumab/platinum fluorouracil containing regimen and t-dxd. no prior her2 targeted therapy. * other cancers: progressed during or after ≥ 1 prior line of systemic therapy for locally advanced unresectable or metastatic disease. no prior her2 targeted therapy. * prior therapies for part 4 (phase 1b dose expansion elvn-002 + trastuzumab + chemotherapy): \* colorectal cancer: candidate for capeox or mfolfox6 and not a candidate for first-line anti-programmed death ligand 1 (pd-(l)-1) treatment (if the tumor is microsatellite instability (msi)-high/deficient mismatch repair (dmmr). no prior therapy for metastatic disease (1 cycle of mfolfox6 or 1 cycle of capeox allowed). no prior her2 targeted therapy. * at least 1 measurable lesion based on recist v 1.1 within 6 weeks before the first dose of elvn-002 (part 3 and part 4 only; phase 1b dose expansion cohorts) * eastern cooperative oncology group (ecog) performance status of 0-1 * adequate hematological, hepatic, renal, and cardiac function exclusion criteria: * treatment with anticancer therapy within a specific time before the first dose: * chemotherapy (including adc) ≤ 3 weeks * immunotherapy ≤ 4 weeks * hormonal therapy ≤ 2 weeks * tki ≤ 2 weeks * any experimental therapy ≤ 3 weeks or 5 half-lives, whichever is longer * radiotherapy-wide therapy ≤ 3 weeks * radiotherapy limited field (including stereotactic brain) ≤ 2 weeks * antibody ≤ 3 weeks * any brain lesion requiring immediate local therapy * ongoing use of corticosteroids for central nervous system (cns) symptoms at a dose of \> 2 mg daily of dexamethasone (or equivalent) * leptomeningeal disease * uncontrolled seizures * participants for any chemotherapy cohort: ongoing grade 2 or higher neuropathy of any cause * inability to swallow pills or any significant gastrointestinal disease that would preclude adequate oral absorption of medications. * ongoing adverse effects from prior treatment \> ctcae grade 1 except for grade 2 alopecia * corrected qt interval (qtc) of \>470 milliseconds (ms) for females or \>450 ms for males

Keywords: elvn-002 her2 positive colorectal cancer her2 overexpression her2