Calquence (acalabrutinib)

P3, N=394, Recruiting, Guangzhou Lupeng Pharmaceutical Company LTD.

P2, N=28, Active, not recruiting, Patrick C. Johnson, MD | Recruiting --> Active, not recruiting

P2, N=96, Completed, BeiGene | Active, not recruiting --> Completed

Covalent BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib) irreversibly bind the C481 residue and have produced high response rates and durable disease control, often replacing chemoimmunotherapy in the relapsed setting and, for some entities, even in the first line. Non-covalent BTK inhibitors (e.g., pirtobrutinib) bind BTK independently of C481, can overcome classic C481-mediated resistance, and extend BTK pathway targeting into later lines of therapy. Overall, BTK inhibition has evolved into a versatile platform enabling long-term, often chemo-free management strategies.

In the phase 3 randomized SEQUOIA study (NCT03336333), zanubrutinib (arm A) demonstrated superior progression-free survival (PFS) compared with bendamustine-rituximab (BR; arm B) in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without del(17p). In the phase 3 AMPLIFY study (NCT03836261), acalabrutinib-venetoclax with or without obinutuzumab demonstrated prolonged PFS vs chemoimmunotherapy (investigator's choice of fludarabine, cyclophosphamide, and rituximab [FCR] or BR) in patients with treatment-naive CLL without del(17p) or TP53 mutations...Zanubrutinib also demonstrated longer PFS whether adjusted for age (PFS-INV hazard ratio &lsqb;HR], 0.26; 95% CI, 0.13-0.54; P<.0003) or unadjusted (PFS-INV HR, 0.45; 95% CI, 0.23-0.88; P=.0197). These results highlight zanubrutinib monotherapy as an effective treatment option for all patients with treatment-naive CLL/SLL, including patients who might otherwise be considered for more intensive fixed-duration combination regimens.

 This survey reveals evidence-based treatment selection and appropriate risk stratification in Indian hematology practice. The predominance of generic acalabrutinib reflects superior safety compared to ibrutinib and cost considerations. Financial constraints driving treatment discontinuation underscore an urgent need for healthcare policy interventions to improve drug accessibility and affordability, ensuring equitable access and optimal outcomes.

P=N/A, N=151, Active, not recruiting, AstraZeneca | Completed --> Active, not recruiting | Trial completion date: Jan 2025 --> Apr 2027 | Trial primary completion date: Jan 2025 --> Apr 2027

P2, N=80, Not yet recruiting, AstraZeneca | Trial completion date: Nov 2032 --> May 2029 | Initiation date: Sep 2025 --> Jan 2026 | Trial primary completion date: Nov 2032 --> May 2029

P1/2, N=72, Recruiting, Austin I Kim | N=53 --> 72 | Trial completion date: Jun 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Jun 2027

P2, N=48, Completed, Acerta Pharma BV | Active, not recruiting --> Completed | Trial completion date: Apr 2026 --> Oct 2025

The primary first-line treatment options for CLL comprise continuous therapies based on the BTK inhibitors ibrutinib, zanubrutinib, or acalabrutinib, or fixed-duration regimens combining the BCL2 inhibitor venetoclax with obinutuzumab or the BTK inhibitors ibrutinib or acalabrutinib (with or without obinutuzumab). Selecting the appropriate targeted therapy requires careful evaluation of a multitude of factors, including molecular disease features (especially del&lsqb;17p]/TP53 and IGHV mutational status), comorbidities, comedications, and the patient's preferences. Focusing on primary treatment options, we review data from the key controlled trials that support the first-line use of targeted therapies for patients with CLL, consider ongoing trials that may support clinical decision-making in the future, and assess the potential to personalize treatment regimens in CLL based on minimal residual disease status.

P2, N=60, Active, not recruiting, Acerta Pharma BV | Trial completion date: Sep 2026 --> Jun 2026