A Study of ASP3082 in Adults With Advanced Solid Tumors
ConditionSolid Tumor
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAstellas Pharma Inc
About this trial
This is an open-label study. This means that people in this study and clinic staff will know that people will receive ASP3082. The study aims to check how safe and well-tolerated ASP3082 is for people with advanced solid tumors that have a specific mutation called KRAS G12D.
This study will be in 2 parts.
In Part 1, different small groups of people will receive lower to higher doses of ASP3082 by itself, or together with cetuximab. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP3082, by itself or together with cetuximab, to use in Part 2 of the study. The first group will receive the lowest dose of ASP3082. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP3082. The panel will do this for each group until all groups have received ASP3082 (by itself or together with cetuximab) or until suitable doses have been selected for Part 2.
In Part 2, ASP3082 will be given in by itself, or in combination with the other study treatments.
Study treatments will be given through a vein. This is called an infusion. Each treatment cycle is 21 or 28 days long. They will continue treatment until: they have medical problems from the treatment they can't tolerate; their cancer gets worse; they start other cancer treatment; or they ask to stop treatment.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented Kirsten rat sarcoma viral oncogene homolog [KRAS] G12D mutation and has received prior standard therapy and the investigator does not see any further clinical benefit from continuing such targeted therapy, or is ineligible to receive standard approved therapies (no limit to the number of prior treatment regimens).
For the ASP3082 monotherapy escalation cohorts, participants with solid tumor malignancies are allowed to be enrolled. Participants with other known KRAS G12 mutations will not be eligible for the study
For ASP3082 combination therapy with Nab-P+GEM or FOLFIRINOX or NALRIFOX: Participant must have mPDAC that has not been previously treated with chemotherapy. If a participant received (neo)adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the (neo)adjuvant therapy.
Participant consents to provide tumor specimen in a tissue block or unstained serial slides or a tumor biopsy (core needle biopsy or excision) obtained after the last interventional treatment, but prior to start of study intervention. Participant also consents to provide a sample for tumor biopsy during the treatment period as indicated in the study protocol. If a participant cannot provide a fresh tissue biopsy sample, the site should consult with the sponsor/study medical monitor.
Disqualifiers
Participant has received investigational therapy within 21 days or 5 half-lives, whichever is shorter, prior to start of study intervention.
Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with asymptomatic, treated CNS metastases are eligible.
Participant has leptomeningeal disease as a manifestation of the current malignancy.
Participant has a prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed.
Trial design
Design model
Sequential
Treatments tested in this trial
Setidegrasib
DrugIntravenous Infusion
Cetuximab
DrugIntravenous Infusion
Leucovorin
DrugIntravenous Infusion
Oxaliplatin
DrugIntravenous Infusion
Fluorouracil
DrugIntravenous Infusion
Irinotecan
DrugIntravenous Infusion
Nanoparticle albumin-bound-paclitaxel
DrugIntravenous Infusion
Gemcitabine
DrugIntravenous Infusion
Docetaxel
DrugIntravenous Infusion
Pembrolizumab
DrugIntravenous Infusion
Cisplatin
DrugIntravenous Infusion
Carboplatin
DrugIntravenous Infusion
Pemetrexed
DrugIntravenous Infusion
Liposomal Irinotecan
DrugIntravenous Infusion
Treatment groups
681 Participants
are divided into 11 treatment groups11
Treatment groupsSee each treatment group below.
Group A: ASP3082 Dose Escalation (Monotherapy Part 1)Experimental treatment 1 intervention
Group B: ASP3082 Dose Expansion (Monotherapy Part 2)Experimental treatment 1 intervention
Group C: ASP3082 + Cetuximab Dose Escalation (Combination Therapy Part 1)Experimental treatment 2 interventions
Group D: ASP3082 + Cetuximab Dose Expansion (Combination Therapy Part 2)Experimental treatment 2 interventions
Group E: ASP3082 China Safety CohortExperimental treatment 1 intervention
Group F: Treatment naive PDAC cohort ASP3082 + FOLFIRINOXExperimental treatment 5 interventions
Group G: Treatment naive PDAC cohort ASP3082 + Nab-Paclitaxel + GemcitabineExperimental treatment 3 interventions
Group H: ASP3082 + Docetaxel - NSCLCExperimental treatment 2 interventions
Group I: ASP3082 + Pembrolizumab - NSCLCExperimental treatment 2 interventions
Group J: ASP3082 + (Cisplatin or Carboplatin) and Pemetrexed +/- Pembrolizumab - NSCLCExperimental treatment 5 interventions
Group K: Treatment naive PDAC cohort ASP3082 + NALIRIFOXExperimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Incidence of Dose Limiting Toxicities (DLTs)
A DLT is defined as any event meeting the DLT criteria excluding toxicities clearly related to disease progression or intercurrent illness or standard of care (SoC) regimens as determined by the investigator.
Time frame
Up to 28 Days2
Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study IP, whether or not considered related to the study investigational product (IP). Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of study IP. This includes events related to the comparator and events related to the (study) procedures.
Time frame
Up to 48 months3
Number of Participants with Serious Adverse Events (SAEs)
An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important events.
Time frame
Up to 48 months4
Number of Participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Time frame
Up to 48 monthsSecondary outcomes
1
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
ORR is defined as the proportion of participants whose best overall response is rated as complete response (CR) or partial response (PR) per RECIST v1.1.
Time frame
Up to 48 months2
Duration of Response (DOR) per RECIST v 1.1
DOR is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date of documented radiological disease progression per RECIST v1.1 or death in the absence of progression.
Time frame
Up to 48 months3
Disease Control Rate (DCR) per RECIST v 1.1
DCR is defined as the proportion of participants whose best overall response is rated as CR, PR or SD based on RECIST v1.1.
Time frame
Up to 48 months4
Pharmacokinetics (PK) of ASP3082 in plasma: Area under the concentration-time curve (AUC)
AUC will be recorded from the PK plasma samples collected.
Time frame
Up to 48 monthsSponsors and contacts
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Source ClinicalTrials.gov