Advanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,Breast Clinical Trial
— DPT01Official title:
A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for the Treatment of Unresectable and/or Metastatic Solid Tumors Harboring HER2 Activating Mutations Regardless of Tumor Histology
| Verified date | April 2024 |
| Source | AstraZeneca |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is an open-label, multi-center, single arm, Phase II study to evaluate the efficacy and safety of T-DXd for the treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology. The target population are patients who have progressed following prior treatment or who have no satisfactory alternative treatment options, including approved second line therapies in the specific tumor type. Pre-specified HER2 mutations will be locally assessed using NGS tests or alternative methods. Prior HER2 targeting therapy is permitted.
| Status | Active, not recruiting |
| Enrollment | 102 |
| Est. completion date | July 14, 2026 |
| Est. primary completion date | January 25, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 120 Years |
| Eligibility | Inclusion Criteria: - Adults =18 years old. Other age restrictions may apply as per local regulations. - Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772_A775dup / A775_G776insYVMA, L755S, G778_P780dup / P780_Y781insGSP, T862A, and V842I locally determined by NGS or a validated nucleic acid-based methodology (eg, qPCR, digital PCR) on tumor tissue, who have progressed following prior treatment or who have no satisfactory alternative treatment options. - Prior HER2 targeted therapy is permitted. - All patients must provide an FFPE tumor sample for retrospective central HER2 testing. - LVEF =50% - ECOG 0-1 - All patients have measurable target disease assessed by the Investigator based on RECIST v1.1 Exclusion Criteria: - HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma. - HER2 mutant NSCLC. - Medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic CHF, unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke. - History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening - Corrected QT interval by Fridericia's formula (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG. - Lung-specific intercurrent clinically significant severe illnesses. - History of active primary immunodeficiency, known HIV, active HBV or HCV infection - Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals - Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). - Has spinal cord compression or clinically active central nervous system metastases. |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Research Site | Anderlecht | |
| Canada | Research Site | Toronto | CA |
| Denmark | Research Site | Copenhagen | |
| France | Research Site | Bordeaux | |
| France | Research Site | Lyon Cedex 08 | |
| France | Research Site | Villejuif Cedex | |
| Italy | Research Site | Milan | |
| Italy | Research Site | Milano | |
| Italy | Research Site | Napoli | |
| Japan | Research Site | Chuo-ku | |
| Japan | Research Site | Kashiwa | |
| Japan | Research Site | Suita-shi | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Spain | Research Site | Barcelona | |
| Spain | Research Site | Madrid | |
| Spain | Research Site | Madrid | |
| Spain | Research Site | Pamplona | |
| Spain | Research Site | Sevilla | |
| United States | Research Site | Boston | Massachusetts |
| United States | Research Site | Boston | Massachusetts |
| United States | Research Site | Commack | New York |
| United States | Research Site | Fairfax | Virginia |
| United States | Research Site | Harrison | New York |
| United States | Research Site | Houston | Texas |
| United States | Research Site | Middletown | New Jersey |
| United States | Research Site | Muncie | Indiana |
| United States | Research Site | New York | New York |
| United States | Research Site | Santa Rosa | California |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca | Daiichi Sankyo Co., Ltd. |
United States, Belgium, Canada, Denmark, France, Italy, Japan, Korea, Republic of, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR) | Confirmed ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR), as determined by ICR per RECIST v1.1. A CR was defined as disappearance of all target lesions (TLs) and PR was defined as at least a 30% decrease in the sum of the diameters (dms) of TL, taking as reference the baseline sum of diameters as long as criteria for PD were not met. An ICR of all radiological imaging data was carried out using RECIST v1.1. All images were collected centrally. The imaging scans were reviewed by 2 independent radiologists and were adjudicated, if required. | Tumor scans performed at screening,then every 6 weeks (q6w) +/- 1 week relative to date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) | |
| Secondary | Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment | DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression (date of progression-free survival [PFS] event or censoring - date of first response + 1). The DoR was calculated using Kaplan-Meier technique. | Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) | |
| Secondary | Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment | DCR at 6 weeks was defined as the percentage of participants who had the best objective response (BoR) of confirmed CR or PR, or who had stable disease (SD) (without subsequent cancer therapy), for at least 5 weeks after first dose of study treatment. DCR at 12 weeks was defined as the percentage of patients who had the BoR of confirmed CR or PR, or who had SD (without subsequent cancer therapy), for at least 11 weeks after first dose of study treatment. CR was defined as disappearance of all TL and PR was defined as at least a 30% decrease in sum of the dms of TL, taking as reference the baseline sum of dms as long as criteria for PD were not met. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (>=20% increase in sum of dms of TLs and an absolute increase of >=5 millimeters, taking as reference smallest sum of dms since treatment started including baseline sum of dms). CI was calculated using Clopper-Pearson method. | Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) | |
| Secondary | PFS as Per RECIST v1.1 Using ICR and Investigator Assessment | PFS was defined as the time from first dose of study treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from assigned therapy or received another anti-cancer therapy prior to progression (i.e. date of PFS event or censoring - date of first dose + 1). PFS was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method. | Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) | |
| Secondary | Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment | Percentage of participants alive and progression-free at 6 and 12 months are reported. It was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method. | At Months 6 and 12 | |
| Secondary | Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment | Confirmed ORR was defined as the percentage of participants who had a confirmed CR or PR as determined by investigator per RECIST v1.1. A CR was defined as disappearance of all TLs and PR was defined as >=30% decrease in the sum of the dms of TL, taking as reference the baseline sum of dms as long as criteria for PD were not met. | Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months) | |
| Secondary | Overall Survival (OS) | OS was defined as the time from the date of first dose of study treatment administration until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy (i.e. date of death or censoring - date of first dose + 1). OS was calculated using the Kaplan-Meier technique. CI for median OS derived based on the Brookmeyer-Crowley method. | From the date of first treatment administration up to death, approximately 24 months | |
| Secondary | Percentage of Participants Alive at 6 and 12 Months | Percentage of participants alive at 6 and 12 months are reported. It was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method. | At Months 6 and 12 | |
| Secondary | Serum Concentrations of T-DXd and Total Anti-HER2 Antibody | Serum samples were collected at specified timepoints to determine serum concentrations of T-DXd and total anti-HER2 antibody. | Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days) | |
| Secondary | Serum Concentrations of Deruxtecan (MAAA-1181a) | Serum samples were collected at specified timepoints to determine serum concentrations of MAAA-1181a. | Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days) | |
| Secondary | Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd | Blood samples were collected to evaluate the presence of ADAs for T-DXd using validated assays. ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. ADA incidence was defined as the percentage of participants who were evaluable for ADA and were treatment-emergent ADA-positive. Treatment-emergent ADA was defined as either treatment-induced (baseline ADA negative, post-baseline ADA positive) or treatment-boosted ADA. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted to >=2 fold during the study period. Persistently positive was defined as >=2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive was defined as having >=1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive. | Up to approximately 24 months |