Phase I/Ib study with the combination of RMC-4630 and LY3214996 in metastatic KRAS mutant CRC, PDAC and NSCLC - The SHERPA-trial

Recruiting

• Conditions: Pancreatic cancer; 10017991

• Registration Number: NL-OMON52379
• Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 55

Inclusion Criteria

1. PART A: Histological or cytological proof of advanced KRASm NSCLC, CRC or
PDAC;
PART B: Histological or cytological proof of advanced PDAC.
2. Age: 18 years and older;
3. Able and willing to give written informed consent;
4. WHO performance status of 0, 1
5. Able and willing to undergo blood sampling for PK and PD analysis;
6. Able and willing to undergo tumor biopsies prior to start (or have undergone
a biopsy within 2 months of
inclusion), while on study treatment and upon progression of disease;
7. Life expectancy > 3 months, allowing adequate follow up of toxicity
evaluation and
antitumor activity;
8. Evaluable disease (PART A and PART B)
9. Women of childbearing potential must have an negative serum pregnancy test
within 14
days prior to registration and agree to use effective contraceptive
thoughout the
treatment period, and for 4 months after the first of study treatment
10. Adequate organ system function

Exclusion Criteria

- Part A: No excluded genotypes
- Part B: Excluded genotypes (including co occurring mutations):
o NRAS (except G12A/C)
o RASQ61
o KRASG13
o BRAF Class 1, 2, or unclassified
o PIK3CA
o STK11
o KEAP1
- Any treatment with investigational drugs within 30 days prior to receiving
the first dose of investigational treatment;
- History of another malignancy
Exception PART A: Patients who have been disease-free for at least 3
years, or patients with a history of completely
resected non-melanoma skin cancer and/or patients with indolent completely
resected second malignancies are eligible.
Exception PART B: Adequately treated carcinoma in situ of the cervix and
adequately treated basal cell carcinoma of the
skin.
- Patients who have had previous treatment with any targeted drug
combination known to interfere RAS/MEK/MAPK
pathway components.
- Woman who are pregnant or breast feeding;
- Unreliable contraceptive methods.
- Patients who have undergone any major surgery within the last 4 weeks
prior to starting study drug or who would not
have fully recovered from previous surgery.
- Radio- or chemotherapy within the last 4 weeks prior to receiving the
first dose of investigational treatment; except a
palliative dose of radiation of 8 Gy, which is allowed up to one week
before study start and should not be applied to the
target lesion.
- Patients with cardiac comorbidities, uncontrolled hypertension, prolonged
QT interval or patients who have had a stroke
within 3 months prior to start study.
- Known hypersensitivity to one of the study drugs or excipients.
- Baseline diarrhea and/or any condition that would impair absorption of
oral agents
- Toxicities related to prior treatments > grade 1 (excluding alopecia)

Study & Design

• Study Type: Interventional
• Study Design: Not specified