Clinical trial NCT07020221: A Phase 1/2a Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors
Official title: A Phase 1/2a, Open-label Study of VS-7375, a KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and in Combination, in Patients With Advanced KRAS G12D-Mutated Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pancreatic Ductal Adenocarcinoma
Non Small Cell Lung Cancer
Colorectal Cancer
Solid Tumor, Adult
G12D Mutated KRAS
Keywords: KRAS G12D mutation
Solid tumors
Non Small Cell Lung Cancer
Lung Cancer
Colorectal Cancer
Metastatic Cancer
Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma
NSCLC
CRC
PDAC
Pancreatic Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Gastrointestinal Neoplasms
KRAS
RAS
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
First posted: 2025-06-13
Enrollment: 130
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 study will assess the safety and efficacy of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation.


Eligibility criteria: Key Inclusion Criteria:

* Individuals ≥18 years of age.
* Agreement to sign and date an informed consent form (ICF) approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
* Histologic or cytologic evidence of locally advanced unresectable or metastatic solid tumor harboring a KRAS G12D mutation.
* Must have received ≥1 prior line of standard systemic therapy for advanced or metastatic disease or experienced cancer progression within 6 months of neoadjuvant or adjuvant therapy.
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate organ function
* Adequate cardiac function
* Recovered from all AEs due to previous therapies to Grade ≤1 or baseline.
* Agreement to use highly effective contraception

Key Exclusion Criteria:

* Underwent major surgical procedure as defined by the Investigator, other than for diagnosis, within 4 weeks prior to Cycle 1 Day 1,
* Receipt of chemotherapy, targeted therapy, or radiotherapy (excluding palliative radiation) within 4 weeks or 5 half-lives, whichever is shorter, or immunotherapy within 4 weeks prior to Cycle 1 Day 1
* Treatment with any investigational drug at least 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.
* History of treatment with direct and specific KRAS G12D inhibitors.
* Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
* Inability to swallow oral medications.
* Evidence or history of uncontrolled, clinically significant hematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation, neurologic, dermatologic, autoimmune, or allergic disease
* Individuals who are pregnant or breastfeeding.

Primary outcomes:
measure: Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375
timeFrame: Up to 2.5 years
measure: Part A: To identify the MTD or MFD
timeFrame: Cycle 1 (each cycle is 21 days)
measure: Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen
timeFrame: Up to 2.5 years
measure: Part C: To characterize the safety, tolerability, and AE profile of the combination of cetuximab with VS-7375
timeFrame: From enrollment to the end of treatment; an average of 9 months
measure: Part C: To identify a recommended VS-7375 dose for subsequent studies of VS-7375 in combination with cetuximab.
timeFrame: Cycle 1 (each cycle is 21 days)
measure: Part D: To determine the preliminary anticancer activity of the optimal cetuximab + VS-7375
timeFrame: Up to 2.5 years
Secondary outcomes:
measure: To characterize the PK of VS-7375 administered on a daily oral schedule
timeFrame: Up to 2.5 years
measure: To characterize the PK of VS-7375 administered on a daily oral schedule
timeFrame: Up to 2.5 years
Other outcomes:
Locations:
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
References: