Clinical trial NCT05382559: A Study of ASP3082 in Adults With Advanced Solid Tumors
Official title: A Phase 1 Study of ASP3082 in Participants With Locally Advanced or Metastatic Solid Tumor Malignancies With KRAS G12D Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: Solid Tumor
Cancer
Malignancy
Metastasis
Pharmacokinetics
ASP3082
KRAS G12D
NSCLC
CRC
PDAC
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2022-05-19
Enrollment: 651
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label study. This means that people in this study and clinic staff will know that they 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: Inclusion Criteria:

* 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 or has refused 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.
* For ASP3082 combination therapy with Nab-P+GEM or FOLFIRINOX: 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 not more than 56 days 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.
* Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Participant has an ECOG performance status of 0, 1 or 2 for dose escalation, and 0 or 1 for dose expansion.
* Participant's last dose of prior antineoplastic therapy, including any immunotherapy, was 21 days or 5 half-lives, whichever is shorter, prior to initiation of study intervention administration.
* Participant has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to the start of study intervention administration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids (NOTE: Physiologic replacement dose of hydrocortisone or its equivalent \[defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone, or up to 10 mg per day of prednisone\] is permitted), and not have active radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<= 2 weeks of radiotherapy) to non-central nervous system disease.
* Participant's adverse events \[AEs\] (excluding alopecia) from prior therapy have improved to grade 1 or baseline within 14 days prior to start of study intervention.
* Participant has adequate organ function as indicated by protocol laboratory value parameters (If a participant has received a recent blood transfusion, the laboratory tests must be obtained \>= 14 days after any blood transfusion.).
* Female participant is not pregnant, confirmed by pregnancy test and medical evaluation by interview, and at least 1 of the following conditions apply:

  * Not a woman of childbearing potential (WOCBP).
  * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after study intervention administration.
* Female participant must agree not to breastfeed starting at screening and throughout the study period and for 6 months after study intervention administration.
* Female participant must not donate ova starting at first dose of study intervention and throughout the study period and for 6 months after study intervention administration.
* Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 3 months after study intervention administration.
* Male participant must not donate sperm during the treatment period and for 3 months after study intervention administration.
* Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 3 months after study intervention administration.
* Participant agrees not to participate in another interventional study while receiving study intervention (Participants who are currently in the follow-up period of an interventional clinical trial are allowed).

Exclusion Criteria:

* 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.
* Participant has a known or suspected hypersensitivity to ASP3082 or any components of the formulation used.
* Participant with active hepatitis B (including acute hepatitis B virus \[HBV\] or chronic HBV) or hepatitis C virus \[HCV\] (ribonucleic acid \[RNA\] detected by qualitative assay). HCV RNA testing is not required in participants with negative HCV antibody testing.
* Participant has a known history of human immunodeficiency virus \[HIV\] infection. No HIV testing is required unless mandated by a local health authority.
* Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study intervention, left ventricular ejection fraction (LVEF) \< 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO) or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker, or long QT syndrome.
* Participant has a corrected QT interval (single electrocardiogram \[ECG\]) using Fridericia's formula (QTcF) \> 450 milliseconds (msec) (men) or \>470 msec (women) during screening.
* Participant has received prior treatment with a specific KRAS G12D inhibitor/degrader or pan-RAS inhibitor/degrader targeting KRAS G12D. Participants who received prior treatment with a KRAS G12D inhibitor/degrader are eligible for the ASP3082 combination therapy cohort.
* Participant has an active infection requiring intravenous antibiotics within 14 days prior to study intervention.
* Participant is expected to require another form of antineoplastic therapy while on study treatment.
* Participant has any condition which makes the participant unsuitable for study participation (such as psychiatric illness/social situations that would limit compliance with study requirements).
* Participant has had major surgery within 4 weeks prior to first dose of study intervention.

For ASP3082 Combination Therapy:

* Prior discontinuation of cetuximab treatment due to toxicity or intolerance of cetuximab.
* History of interstitial lung disease requiring systemic steroid treatment. Note that a participant with resolved pulmonary infections or radiation pneumonitis is eligible.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: Up to 21 Days
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 48 months
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to 48 months
measure: Number of Participants with laboratory value abnormalities and/or adverse events (AEs)
timeFrame: Up to 48 months
measure: Number of Participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs)
timeFrame: Up to 48 months
measure: Number of Participants with vital sign abnormalities and/or adverse events (AEs)
timeFrame: Up to 48 months
measure: Number of Participants with physical exam abnormalities and/or adverse events
timeFrame: Up to 48 months
measure: Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status
timeFrame: Up to 48 months
Secondary outcomes:
measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Up to 48 months
measure: Duration of Response (DOR) per RECIST v 1.1
timeFrame: Up to 48 months
measure: Disease Control Rate (DCR) per RECIST v 1.1
timeFrame: Up to 48 months
measure: Pharmacokinetics (PK) of ASP3082 in plasma: Area under the concentration-time curve (AUC)
timeFrame: Up to 48 months
measure: PK of ASP3082 in plasma: Maximum Concentration (Cmax)
timeFrame: Up to 48 months
measure: PK of ASP3082 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)
timeFrame: Up to 48 months
measure: PK of ASP3082 in plasma: Time of maximum concentration (tmax)
timeFrame: Up to 48 months
measure: Changes in Kirsten rat sarcoma (KRAS) viral oncogene homolog G12D in tumor samples
timeFrame: Up to 48 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Santa Monica
country: United States
facility: UCLA Santa Monica Hematology Oncology
state: California
city: Denver
country: United States
facility: Denver HealthONE Drug Development Unit
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Center at Yale New Haven Hospital
state: Connecticut
city: Lake Mary
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists & Research Institute Sarasota
state: Florida
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University - Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Western
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology - Virginia Cancer Specialists
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital
state: Wisconsin
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Xuhui District
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: La Tronche
country: France
facility: Site FR33003
state: Grenobele
city: Bordeaux
country: France
facility: Site FR33002
city: Lyon
country: France
facility: Site FR33001
city: Lyon
country: France
facility: Site FR33005
city: Villejuif
country: France
facility: Site FR33004
state: Île-de-France
city: Nagoya
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama
country: Japan
facility: Shikoku Cancer Center
state: Ehime
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
state: Tokyo
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Seongnam-si
country: Korea, Republic of
facility: Site KR82002
state: Gyeonggi-do
city: Jongno -Gu
country: Korea, Republic of
facility: Site KR82001
state: Seoul
city: Seodaemun-gu
country: Korea, Republic of
facility: Site KR82003
state: Seoul
city: Songpa-gu
country: Korea, Republic of
facility: Site KR82004
state: Seoul
city: Barcelona
country: Spain
facility: Site ES34001
city: Madrid
country: Spain
facility: Site ES34004
city: Málaga
country: Spain
facility: Site ES34002
city: Sevilla
country: Spain
facility: Site ES34003
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: