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HERTHENA-PanTumor01 (U31402-277): A Phase 2, Multicenter, Multicohort, Open-Label, Proof of Concept Study of Patritumab Deruxtecan (HER3-DXd; U3-1402) in Subjects with Locally Advanced or Metastatic Solid Tumors (HERTHENA-PanTumor01)

Phase 2 Study of HER3-DXd in Locally Advanced or Metastatic Solid Tumors (HERTHENA-PanTumor01)

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial_jp@daiichisankyo.com

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial_jp@daiichisankyo.com

Recruiting

Feb. 01, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Sign and date the informed consent form prior to the start of any study-specific qualification procedures. A separate tissue screening consent will be obtained from all subjects to meet the baseline tumor tissue requirement.
2. Participants aged >=18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).

3. Has locally advanced unresectable or metastatic disease (not curable by surgery or radiation) as follows:
3-1. Cutaneous (acral and non-acral) melanoma
- Histologically or cytologically confirmed cutaneous (acral or non-acral) melanoma
- Disease progression while on or after having received treatment with >=1 prior line of anti-PD-1 or anti-PD-L1 based therapy (previous use of other ICIs [ie, anti-CTLA4, anti- LAG-3] is acceptable). Prior anti-PD-(L)1 therapy in the adjuvant setting is allowed if there is recurrence within 12 weeks of the last dose. If the participant had BRAFm melanoma, they must have had disease progression on BRAF/MEK inhibitor therapy as well.
3-2. Squamous cell carcinomas of the head and neck
- Squamous cell carcinoma of the head and neck (with a primary location of oral cavity, oropharynx, larynx, hypopharynx) that is HPV positive or negative (as determined by local standard). Excludes tumor location in the nasopharynx, nasal cavity, paranasal sinuses, and unknown primary locations.
- Disease progression after having received treatment with >=1 and <3 prior lines of systemic therapy in the unresectable recurrent or metastatic setting.
Must have had disease progression on anti-PD-(L)1 (either as monotherapy or in combination with chemotherapy or other therapies). Must also have had disease progression on a PBC regimen either in the recurrent or metastatic setting or in the locally advanced setting with curative intent.
3-3. Gastric or GEJ adenocarcinoma
- Tumor tissue must be confirmed as negative for HER2 expression (IHC 0/1+ or IHC 2+/in situ hybridization negative) as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
- Disease progression after having received treatment with >=2 prior lines of therapy that include PBC.
3-4. Ovarian Carcinoma
- Pathologically documented high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
- Documented disease progression >=4 weeks after the last dose of PBC and <6 months of last dose of PBC in the advanced or metastatic setting.
3-5. Cervical Cancer
- Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix.
- Disease progression after having received >=1 line of systemic therapy in the recurrent or metastatic setting.
3-6. Endometrial Cancer
- Pathologically or cytologically documented endometrial cancer (carcinoma of any histological sub-type or endometrial carcinosarcoma).
- Documented disease progression after having received >=1 prior line of therapy (maximum of 3) PBC containing systemic treatment and an anti-PD(L)-1 therapy-containing regimen (combined or sequential) in the advanced/metastatic setting.
3-7. Bladder Cancer
- Pathologically or cytologically documented locally advanced/unresectable or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is predominant. Small cell/neuroendocrine tumors are not allowed even if mixed histology.
- Relapsed or progressed after treatment with >=1 prior line of therapy (maximum of 3) that contains anti-PD-(L)1 therapy in the perioperative or metastatic setting. At least 1 line of therapy must also contain one of the following treatment modalities: chemotherapy or enfortumab vedotin.
3-8. Esophageal Carcinoma
- Pathologically or cytologically documented esophageal squamous cell carcinoma.
- Must have documented disease progression after having received 2 prior lines of therapy including previous PBC.
3-9. Pancreatic Carcinoma
- Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma.
- Relapsed or disease progression after having received 1 prior line of systemic therapy in the locally advanced/metastatic setting.
3-10. Prostate Cancer
- Pathologically or cytologically documented unresectable locally advanced or metastatic CRPC.
- Adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
- Surgically or medically castrated, with testosterone levels of <50 ng/dL.
- Documented objective progression as determined by radiographic progression for subjects with measurable disease after androgen deprivation.
- Relapsed or disease progression after having received treatment with >=1 of the following novel hormonal agents: abiraterone, enzalutamide, apalutamide, or darolutamide.
- Relapsed or disease progression after having received >=1 cytotoxic chemotherapy regimen that included a taxane.
3-11. Gastric Cancer 2L
- Must have had gastric or GEJ adenocarcinoma confirmed as negative for HER2 expression (IHC 0/1+ or IHC 2+/in situ hybridization negative) as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
- Disease progression after having received treatment with only 1 prior line of systemic anti-cancer therapy that includes 5-FU-based chemotherapy with or without an anti-PD-1 therapy. For subjects whose tumors are claudin (CLDN) 18.2 positive, treatment with 5-FU based chemotherapy with CLDN18.2 directed therapy in the first-line setting is allowed.
3-12. Non-small Cell Lung Cancer (NSCLC)
- Histologically or cytologically documented metastatic or locally advanced nonsquamous NSCLC not amenable to curative surgery or radiation.
- Documentation of absence of actionable driver mutation (ie, ALK rearrangement, BRAF V600E mutation, EGFR-activating mutations [exon 19 deletion or L858R mutation], EGFR exon 20 insertion mutation, HER2 mutation, KRAS G12C mutation, MET exon 14 skipping mutation, NTRK 1/2/3 gene fusion, RET rearrangement, or ROS1 rearrangement). New testing for these genomic alterations is not required for Screening.
- Relapsed or disease progression after receiving only anti-PD-(L)1 and PBC (ie, platinum doublet) administered in combination or sequentially for metastatic disease.
3-13. Breast Cancer
- Pathologically documented breast cancer that is assessed as HER2 negative (IHC2+/ISH-, IHC1+, or IHC0 per ASCO/CAP guidelines), and HR positive (either ER and/or PgR positive [ER or PgR >=1%] per ASCO/CAP guidelines). The HER2 and HR results must be from a tumor sample obtained in the metastatic setting.
- Participant must have received one line of chemotherapy for mBC, but not more than one line and must have a clinically or radiologically documented evidence of tumor progression on or after CDK 4/6 inhibitor combined with endocrine therapy; previous treatments with PI3K inhibitors, mTOR inhibitors, PKB inhibitors also known as AKT-inhibitors and PARP-inhibitors are allowed.

4. Has >=1 measurable lesion on CT or MRI as per RECIST v1.1 by investigator assessment. Prostate cancer participants with bone only disease may be eligible.
5. Provides a pretreatment tumor tissue sample that meets 1 of the following collection requirements:
- Tumor biopsy from >=1 lesion not previously irradiated and performed since progression with the most recent systemic cancer therapy regimen and prior to signature of the tissue ICF.
OR
- Newly obtained pretreatment tumor biopsy from >=1 lesion not previously irradiated and amenable to sampling, after signature of tissue ICF.
6. Has ECOG PS of 0 or 1 at screening.

1. Has HER2-positive gastric cancer as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
2. Has nasopharyngeal cancer.
3. Has mucosal or uveal melanoma.
4. Has a history of (non-infectious) interstitial lung disease (ILD), that required corticosteroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
5. Has clinically severe respiratory compromise (based on the investigator's assessment) resulting from intercurrent pulmonary illnesses
6. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone daily or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1.
Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
7. Had prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
8. Has history of other active malignancy within 3 years prior to Cycle 1 Day 1, except the following:
a. Adequately treated nonmelanoma skin cancer
b. Adequately treated intraepithelial carcinoma of the cervix
c. Any other curatively treated in situ disease
9. Has any evidence of severe or uncontrolled diseases (eg, active bleeding diatheses, active serious infection) psychiatric illness/social situations, geographical factors, substance abuse, or other factors that, in the investigator's opinion, make it high risk for the subject to participate in the study or that would jeopardize compliance with the protocol
10. Has previously received topoisomerase-1 inhibitors (e.g., irinotecan) treatment in the advanced or metastatic disease setting.

Both

Locally Advanced or Metastatic Solid Tumors

Patritumab deruxtecan (HER3-DXd) will be administered as an intravenous solution every 3 weeks on Day 1 of each 21-day cycle at a dose of 5.6 mg/kg.

- All Cohorts Except Prostate Cancer Cohort
Objective Response Rate (ORR) as assessed by the investigator per RECIST v1.1
- Prostate Cancer Cohort Only
Proportion of Participants Achieving a >=50% Decrease in PSA (PSA50 response rate)

- All Cohorts Except Prostate Cancer Cohort
Treatment-emergent adverse events (TEAEs) and other safety parameters during the study, duration of response (DOR), clinical benefit rate (CBR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS), PK endpoints (serum concentrations and PK parameters of HER3-DXd), correlation between HER3 protein expression at baseline and efficacy
- Prostate Cancer Cohort Only
Treatment-emergent adverse events (TEAEs) and other safety parameters during the study, radiographic progression-free survival (rPFS) as assessed by Prostate Cancer Working Group 3(PCWG3), overall survival (OS), serum concentration of PSA (PSA30 response rate), time to first subsequent anticancer therapy or death(time to first subsequent anticancer therapy :TFST), Time to first symptomatic skeletal-related event (SSRE), PK endpoints (serum concentrations and PK parameters of HER3-DXd), correlation between HER3 protein expression at baseline and efficacy

+81-3-3520-0111

Feb. 07, 2024

Yes

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