The follicular lymphoma trial landscape in 2026
Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, affecting approximately 15,000 Americans annually. Despite being classified as incurable with standard therapy, most patients have a prolonged disease course — median survival now exceeds 18–20 years — driven by rituximab-based regimens, bendamustine combinations, and increasingly, novel immunotherapies. The treatment landscape has undergone two major inflections in recent years: the December 2022 FDA approval of mosunetuzumab (Lunsumio), the first bispecific T-cell engager approved for any lymphoma, and the March 2023 approval of zanubrutinib for relapsed/refractory FL. These approvals did not resolve the competitive race — they intensified it.
In 2026, the strategic question dominating the FL trial landscape is whether bispecific T-cell engagers can move from 3rd-line relapsed/refractory disease into earlier lines — potentially into first-line treatment where the largest patient populations and commercial opportunities reside. AstraZeneca's surovatamig Phase 3 (NCT06549595) is the most consequential trial testing this hypothesis, and it is actively recruiting. Simultaneously, a new generation of BTK degraders is entering Phase 1/2 trials, and Novartis's tisagenlecleucel CAR-T is in an active Phase 3 against standard of care. Follicular lymphoma in 2026 is a field in transition.
The bispecific antibody race: from 3rd line to first line
The approval of mosunetuzumab (Lunsumio) created a new treatment category in follicular lymphoma and triggered immediate follow-on programs. Mosunetuzumab is a CD3xCD20 bispecific T-cell engager — it simultaneously binds CD3 on T cells and CD20 on malignant B cells, redirecting cytotoxic T cells to kill the lymphoma without requiring prior sensitization. The clinical profile was compelling: 80% overall response rate, 60% complete response rate, and fixed-duration dosing (17 cycles, then stop) — an important differentiator in an era when many therapies require indefinite treatment.
AstraZeneca surovatamig Phase 3 in first-line FL (NCT06549595) — started Aug 2024
The most significant trial in the follicular lymphoma field in 2026 is AstraZeneca's surovatamig (AZD0486) Phase 3 in previously untreated patients (NCT06549595). Started August 2024, this trial tests surovatamig plus rituximab against standard of care in first-line FL — a setting where no bispecific has yet been approved. Surovatamig is AstraZeneca's CD3xCD20 bispecific, being evaluated both in this first-line Phase 3 and in an earlier Phase 1 expansion in B-cell NHL (NCT04594642, started March 2021). A positive result from the Phase 3 would represent the first bispecific T-cell engager approved for frontline follicular lymphoma — a category-defining event. AstraZeneca's investment across both early (Phase 1 expansion) and late (Phase 3) stages indicates high confidence in the mechanism.
NCI Phase 3: mosunetuzumab vs. rituximab in low tumor burden FL (NCT06337318) — started Oct 2024
The National Cancer Institute is running a Phase 3 trial (NCT06337318, started October 2024) comparing mosunetuzumab to rituximab in patients with low tumor burden follicular lymphoma — a population typically managed with watch and wait or single-agent anti-CD20 therapy. This trial is asking whether the superior response rates of bispecific T-cell engagers extend to an even earlier setting than approved. Low tumor burden FL represents a large untapped indication; a positive result would expand mosunetuzumab's approved use significantly beyond its current 3rd-line and later label.
Regeneron odronextamab Phase 3 vs. lenalidomide + rituximab (NCT06149286) — started Dec 2023
Regeneron's odronextamab is another CD3xCD20 bispecific T-cell engager competing with mosunetuzumab and surovatamig in the R/R FL space. The Phase 3 trial (NCT06149286, started December 2023) compares odronextamab plus lenalidomide against rituximab plus lenalidomide in relapsed/refractory FL and marginal zone lymphoma — testing the combination approach that adds lenalidomide's immunomodulatory activity to the bispecific. This study also includes marginal zone lymphoma, a closely related indolent B-cell lymphoma that shares many treatment approaches with FL. Three Phase 3 bispecific trials in FL running concurrently represent an unusually crowded competitive environment.
Track follicular lymphoma trials automatically
Get daily alerts when new trials post or existing studies update. Monitor surovatamig, odronextamab, zanubrutinib, and all bispecific programs in follicular lymphoma.
Get Free AlertsBTK inhibitors and the next generation: BTK degraders
BTK inhibitors became a core treatment for relapsed/refractory B-cell malignancies over the past decade. Zanubrutinib's March 2023 FDA approval for R/R FL (after the ROSEWOOD Phase 2 trial) established the third-generation BTK inhibitor as a standard option. But the BTK inhibitor story in FL may be transitional — a new class, BTK degraders (PROTACs), is entering Phase 1/2 trials with a potentially broader activity profile that includes cases resistant to covalent BTK inhibitors.
BeiGene zanubrutinib Phase 3 vs. lenalidomide + rituximab in R/R FL (NCT05100862) — started Mar 2022
BeiGene (now BeOne Medicines commercially in the US) is running a Phase 3 trial (NCT05100862, started March 2022) comparing zanubrutinib plus an anti-CD20 antibody against lenalidomide plus rituximab in relapsed/refractory FL and marginal zone lymphoma. Zanubrutinib's approval was based on a Phase 2 study; this Phase 3 establishes the larger evidence base. The comparator arm — lenalidomide plus rituximab — is the AUGMENT regimen, an established standard. Head-to-head data positioning zanubrutinib against R2 would clarify where it fits in the treatment algorithm.
BeOne BGB-16673 BTK PROTAC Phase 1/2 (NCT05006716) — started Sep 2021
BGB-16673 is BeOne Medicines' BTK PROTAC (Proteolysis Targeting Chimera) — a degrader that eliminates the BTK protein entirely through the ubiquitin-proteasome pathway, rather than just inhibiting its kinase activity. This mechanistic distinction matters because the dominant BTK inhibitor resistance mutation (BTK C481S) prevents covalent binding but does not prevent degradation. BGB-16673 (NCT05006716, Phase 1/2, started September 2021) is being evaluated across B-cell malignancies including FL. Early data have shown activity including in patients with prior BTK inhibitor exposure — the key commercial hypothesis for next-generation BTK degraders.
Nurix NX-2127 and NX-5948: two BTK degrader programs in Phase 1
Nurix Therapeutics is running two separate Phase 1 trials of BTK degraders in B-cell malignancies — NX-2127 (NCT04830137, started May 2021) and NX-5948 (NCT05131022, started April 2022). Both are being evaluated in R/R B-cell malignancies including FL. NX-2127 is designed as a bifunctional molecule that both degrades BTK and recruits Ikaros/Aiolos for degradation — targeting multiple nodes simultaneously. NX-5948 is a selective BTK degrader. The two parallel programs allow Nurix to compare mechanisms and optimize differentiation from competitors including BGB-16673 and established BTK inhibitors.
CAR-T cell therapy: entering Phase 3 for follicular lymphoma
CAR-T cell therapy in follicular lymphoma moved from investigational to approved with the axicabtagene ciloleucel (Yescarta) approval for R/R large B-cell lymphoma, then extended to indolent NHL. In 2026, the most significant CAR-T development for FL specifically is Novartis's Phase 3 comparing tisagenlecleucel to standard of care — an active but no-longer-enrolling study that will yield definitive data on whether CAR-T belongs in the FL treatment algorithm.
Novartis tisagenlecleucel Phase 3 vs. standard of care in R/R FL (NCT05888493) — started Oct 2023
NCT05888493 (started October 2023) is a Phase 3 trial from Novartis comparing tisagenlecleucel (Kymriah) to physician's choice standard of care in adults with relapsed or refractory follicular lymphoma. The trial is now active but no longer enrolling, meaning it has reached its target enrollment and the primary endpoint readout is pending. Tisagenlecleucel is already approved in DLBCL and pediatric ALL; positive Phase 3 data in FL would support a label expansion into this indication, competing with mosunetuzumab-based approaches for the R/R patient population.
CD79b-19 CAR-T at MGH (NCT06026319) — started Oct 2023
Massachusetts General Hospital's Dr. Marcela Maus is running a Phase 1 study (NCT06026319, started October 2023) of CD79b-19 CAR-T cells — a dual-targeting CAR construct targeting both CD79b and CD19 on B-cell malignancies. CD79b is a component of the B-cell receptor complex; dual targeting may reduce the risk of antigen escape that has been observed with single-target CD19 CAR-T. This academic program is evaluating the approach across non-Hodgkin lymphomas including FL. If early results show activity, it could advance toward industry-sponsored development.
Other actively recruiting programs
Loncastuximab tesirine plus rituximab Phase 2 in R/R FL (NCT04998669) — started Feb 2022
This Phase 2 investigator-sponsored study from Dr. Juan Alderuccio at the University of Miami (NCT04998669, started February 2022) evaluates loncastuximab tesirine — an antibody-drug conjugate targeting CD19 conjugated to a pyrrolobenzodiazepine (PBD) dimer toxin — in combination with rituximab for relapsed/refractory FL. Loncastuximab tesirine (Zynlonta) is approved for DLBCL; this study extends it to the indolent FL setting. ADC approaches in FL have been understudied relative to bispecifics and BTK inhibitors, and this study fills a mechanistic gap in the evidence base.
Glofitamab plus obinutuzumab Phase 2 (NCT05783596) — active, not enrolling
A Phase 2 study combining glofitamab (Genentech's CD3xCD20 bispecific, approved for DLBCL) with obinutuzumab (type II anti-CD20) is active but no longer recruiting (NCT05783596, started July 2023). This combination tests whether adding a type II anti-CD20 antibody — which elicits superior direct cell death compared to rituximab — enhances the activity of bispecific T-cell engager therapy in FL and marginal zone lymphoma. Results will inform whether combination bispecific-antibody approaches are superior to bispecific monotherapy.
Actively recruiting and active follicular lymphoma trials (2026)
| NCT ID | Sponsor | Phase | Setting / Agent | Status | Start |
|---|---|---|---|---|---|
| NCT06549595 | AstraZeneca | Phase 3 | 1L FL — Surovatamig + rituximab | Recruiting | Aug 2024 |
| NCT06337318 | NCI | Phase 3 | Low TB FL — Mosunetuzumab vs rituximab | Recruiting | Oct 2024 |
| NCT06149286 | Regeneron | Phase 3 | R/R FL — Odronextamab + Len vs R2 | Recruiting | Dec 2023 |
| NCT05100862 | BeiGene / BeOne | Phase 3 | R/R FL — Zanubrutinib + anti-CD20 vs R2 | Recruiting | Mar 2022 |
| NCT05006716 | BeOne Medicines | Phase 1/2 | R/R B-cell — BGB-16673 BTK PROTAC | Recruiting | Sep 2021 |
| NCT04830137 | Nurix Therapeutics | Phase 1 | R/R B-cell — NX-2127 BTK degrader | Recruiting | May 2021 |
| NCT05131022 | Nurix Therapeutics | Phase 1 | R/R B-cell — NX-5948 BTK degrader | Recruiting | Apr 2022 |
| NCT04594642 | AstraZeneca | Phase 1 | B-cell NHL — AZD0486 (surovatamig) | Recruiting | Mar 2021 |
| NCT06026319 | MGH / Maus Lab | Phase 1 | NHL — CD79b-19 CAR-T | Recruiting | Oct 2023 |
| NCT04998669 | Alderuccio / U. Miami | Phase 2 | R/R FL — Loncastuximab + rituximab | Recruiting | Feb 2022 |
| NCT07473167 | TICAROS | Phase 1/2 | R/R large B-cell NHL — TC011 CAR-T | Recruiting | Aug 2023 |
| NCT05888493 | Novartis | Phase 3 | R/R FL — Tisagenlecleucel vs SoC | Active, not recruiting | Oct 2023 |
| NCT04246086 | Hoffmann-La Roche | Phase 1/2 | FL — Mosunetuzumab + lenalidomide | Active, not recruiting | Aug 2020 |
| NCT05783596 | Merryman / DFCI | Phase 2 | FL/MZL — Glofitamab + obinutuzumab | Active, not recruiting | Jul 2023 |
Competitive dynamics: a three-way Phase 3 race in bispecifics
The follicular lymphoma field has three Phase 3 bispecific T-cell engager trials running concurrently — AstraZeneca's surovatamig in first-line (NCT06549595), Regeneron's odronextamab in R/R (NCT06149286), and NCI's mosunetuzumab vs. rituximab in low tumor burden (NCT06337318). This kind of competitive concentration in a single mechanism is unusual in oncology and reflects both the magnitude of the mosunetuzumab approval signal and the difficulty of differentiating in 3rd-line relapsed/refractory disease. The competition is rational: the FDA approval bar is high enough that multiple bispecifics may be approved, but the commercial opportunity concentrates around whichever agent establishes first-line use.
AstraZeneca's position is particularly notable. Its surovatamig is simultaneously in Phase 1 expansion across B-cell NHL (NCT04594642) and Phase 3 in first-line FL (NCT06549595). Moving directly into a first-line Phase 3 reflects confidence in Phase 1/2 data and positions AstraZeneca to leapfrog mosunetuzumab's current approval if the frontline trial is positive. First-line FL is also a larger, earlier, and more commercially attractive population than 3rd-line and later.
The BTK degrader story adds a parallel track. BGB-16673 (BeOne), NX-2127 and NX-5948 (Nurix) are all in active Phase 1/2 development. If BTK degraders demonstrate activity in BTK-inhibitor-refractory disease — the key clinical hypothesis — they could carve out a niche after bispecifics, creating a sequential treatment algorithm: chemoimmunotherapy → BTK inhibitor → BTK degrader or bispecific. Early activity signals from these programs are among the most watched developments in indolent lymphoma.
Why monitor follicular lymphoma trials?
Follicular lymphoma is a high-velocity trial environment where regulatory and competitive developments can shift rapidly:
- First-line bispecific approval inflection: AstraZeneca's surovatamig Phase 3 is the highest-stakes ongoing trial in FL. Enrollment progress, interim safety data, or protocol amendments are early signals of the trial's trajectory.
- CAR-T vs. bispecific competition: Novartis's tisagenlecleucel Phase 3 has finished enrolling — results will directly compare CAR-T to standard of care and position it against the bispecific approaches for the same R/R FL patients.
- BTK degrader Phase 1 readouts: BGB-16673, NX-2127, and NX-5948 are in active Phase 1/2 evaluation. Dose-expansion results and initial efficacy data from these programs will establish whether BTK PROTACs deliver on their mechanistic promise in FL.
- NCI low tumor burden Phase 3: If mosunetuzumab outperforms rituximab in low tumor burden FL (NCT06337318), the implication for watch-and-wait management of early FL would be significant — and would affect commercial strategy for all competing bispecifics.
- Competitive crowding risk: Three Phase 3 bispecific trials means at least two sponsors may invest in programs that face approved competitors at readout. Early signals of enrollment pace or protocol changes can indicate sponsor confidence.
Get daily follicular lymphoma trial alerts
Track surovatamig, odronextamab, zanubrutinib, tisagenlecleucel, and all FL programs automatically. Free plan monitors key keywords; paid plans add competitor tracking and daily digests.
Start Free — No Credit CardRelated clinical trial monitors
Follicular lymphoma is part of the broader B-cell lymphoma landscape. Related monitors on DataLookout:
- CLL clinical trials — chronic lymphocytic leukemia shares BTK inhibitor and bispecific mechanisms; zanubrutinib, acalabrutinib, and venetoclax programs overlap
- Multiple myeloma clinical trials — BCMA-targeted CAR-T and bispecific programs in myeloma inform FL cell therapy development
- Amyloidosis clinical trials — AL amyloidosis shares plasma cell biology with FL; BTK inhibitors and bispecifics are studied across both conditions
- AML clinical trials — acute myeloid leukemia programs; shared BTK pathway targeting and CAR-T infrastructure