By Fineline Cube Merck Sharp & Dohme Inc. (MSD, NYSE: MRK) announced the initiation of KANDLELIT‑007, a Phase 3 clinical trial evaluating calderasib (MK‑1084), an investigational oral selective KRAS G12C inhibitor, in combination with KEYTRUDA QLEX (pembrolizumab + berahyaluronidase alfa-pmph) for the first‑line treatment of patients with KRAS G12C‑mutant, advanced or metastatic nonsquamous non‑small cell lung cancer (NSCLC).
Clinical Trial Design
| Item | Detail |
|---|---|
| Study Name | KANDLELIT‑007 (NCT07190248) |
| Phase | Phase 3 |
| Design | Randomized, unblinded open‑label, multicenter |
| Population | Newly diagnosed KRAS G12C‑mutant advanced/metastatic nonsquamous NSCLC |
| Enrollment | ~675 patients globally |
| Regimen | Calderasib (oral QD) + KEYTRUDA QLEX (SC) vs. KEYTRUDA QLEX + pemetrexed + carboplatin/cisplatin (IV) |
| Primary Endpoint | Progression‑free survival (PFS) in PD‑L1 TPS ≥ 1% patients |
| Key Secondary Endpoints | PFS in all participants, OS, ORR, DOR, safety (PD‑L1 ≥ 1% and all comers) |
Product Profile
Calderasib (MK‑1084):
- Mechanism: Potent, specific, covalent KRAS G12C inhibitor
- Administration: Oral once daily
KEYTRUDA QLEX:
- Fixed‑combination: Pembrolizumab (PD‑1 blocker) + berahyaluronidase alfa
- Mechanism: Hyaluronidase enhances dispersion for subcutaneous pembrolizumab delivery
Synergistic Rationale: KRAS G12C inhibition sensitizes tumors to PD‑1 blockade, while SC administration improves patient convenience.
Market Opportunity: KRAS G12C NSCLC
Disease Burden:
- Global Incidence: ~45,000 KRAS G12C‑mutant NSCLC cases annually (US: 13,000; China: 18,000)
- Current Standard: Chemo‑immunotherapy (ORR ≈ 30‑40%, mPFS ≈ 6 months)
- Market Size: ¥8‑10 billion China opportunity; $3‑4 billion US opportunity by 2030
Competitive Landscape:
- Sotorasib (Amgen) and adagrasib (Mirati/BMS) approved for later lines only
- No approved first‑line KRAS G12C therapy globally
Financial Implications
Investment: Merck will allocate USD 250‑300 million for KANDLELIT‑007 trial execution.
Peak Sales Potential: If successful, the combination could generate $2‑3 billion globally, with KEYTRUDA franchise benefiting from extended lifecycle.
Forward‑Looking Statements
This brief contains forward‑looking statements regarding clinical trial outcomes, regulatory timelines, and market penetration for calderasib and KEYTRUDA QLEX. Actual results may differ materially.-Fineline Info & Tech