For patients with metastatic colorectal cancer (mCRC) whose disease has outlasted fluoropyrimidines, oxaliplatin, irinotecan and anti-VEGF therapy, the options are thin. Single-agent standards such as regorafenib, trifluridine/tipiracil (TAS-102) and fruquintinib have historically produced response rates of only around 1% to 2%.
That is the backdrop for today's news. AbbVie announced that the FDA has granted two Breakthrough Therapy Designations (BTDs) to telisotuzumab adizutecan (Temab-A, ABBV-400), an investigational c-Met-directed antibody-drug conjugate (ADC). They are the first BTDs for the drug and bring the number of BTDs across AbbVie's ADC portfolio to four.
What Was Designated #
The first designation covers Temab-A in combination with bevacizumab for adults with refractory metastatic colorectal cancer who have previously received a fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF antibody and, if indicated, an anti-EGFR antibody.
The second covers Temab-A as monotherapy for adults with locally advanced or metastatic, EGFR wild-type, c-Met protein-expressing, non-squamous NSCLC who have previously received platinum-based chemotherapy and an anti-PD-(L)1 antibody.
Both designations were based primarily on the first-in-human Phase 1 study M21-404 (NCT05029882). Breakthrough status means the FDA sees early evidence worth speeding up. It is not an approval and does not establish that the drug works.
The Colorectal Data #
The CRC findings come from the combination cohort presented at ESMO 2025 (data cutoff May 29, 2025). The cohort enrolled biomarker-unselected patients with third-line or later disease. After a safety lead-in, patients in a dose-optimization phase were randomly assigned to Temab-A at 2.0 or 2.4 mg/kg plus bevacizumab, or to the standard-of-care combination of TAS-102 plus bevacizumab.
- At 2.4 mg/kg plus bevacizumab (n=30): Median progression-free survival (PFS) was 6.8 months, compared with 4.2 months for TAS-102 plus bevacizumab (n=20). Median overall survival was not reached in the Temab-A arm and was 9.6 months in the control arm.
- At 2.0 mg/kg plus bevacizumab (n=26): Median PFS was 5.6 months and median overall survival was 9.8 months.
These are encouraging numbers, but they need careful reading. The arms are small, the dose-optimization phase was not designed to prove superiority, and the confidence intervals are wide. This is a signal, not a result.
The Lung Cancer Data #
In patients with EGFR wild-type non-squamous NSCLC in the same study (n=48), the objective response rate was 47.9%. Responses were enriched in patients with higher c-Met protein expression.
Safety #
In the pooled Temab-A group (n=63), the most notable toxicities were hematologic:
- Grade ≥ 3 Anemia: Occurred in 37% of patients.
- Grade ≥ 3 Neutropenia: Occurred in 16% of patients.
- Grade ≥ 3 Thrombocytopenia: Occurred in 5% of patients.
These events were dose dependent and became more frequent at higher doses. Nausea (60%, all grade 1 or 2), fatigue (41%) and vomiting (40%) were also common.
Interstitial lung disease (ILD) is a known concern with topoisomerase-1 ADCs. Adjudicated ILD or pneumonitis occurred in 5% of patients (n=3). One case was grade 3, and there were no grade 4 or 5 events.
How the Drug Differs from Its Predecessor #
Temab-A is AbbVie's second c-Met ADC. The first, telisotuzumab vedotin (Emrelis), received FDA accelerated approval in 2025 for previously treated EGFR wild-type non-squamous NSCLC with high c-Met overexpression. It carries an auristatin (MMAE) payload that blocks microtubules.
Temab-A instead carries a novel topoisomerase-1 inhibitor payload. The rationale for this class is that the released drug can diffuse into neighboring tumor cells, including those with low c-Met expression, which might matter in heterogeneous tumors. That design intent has not been demonstrated clinically for this molecule.
The bevacizumab pairing rests on a similar hypothesis. VEGF inhibition may normalize leaky tumor vessels and reduce interstitial pressure, which could help large molecules like ADCs penetrate dense tumors. It is a plausible idea, but this study was not built to prove it.
What Comes Next #
The key test is the Phase 3 AndroMETa-CRC trial (NCT07525206), an open-label, randomized, global study comparing Temab-A plus bevacizumab with TAS-102 plus bevacizumab in refractory mCRC. Its primary endpoints are objective response rate and overall survival. Key secondary endpoints include overall survival stratified by c-Met expression, which will show how much biomarker testing matters in practice.
Until those results arrive, the designations are best read as a sign of promise and not as a new standard of care.
Sources & References #
- AbbVie Press Release (October 7, 2026)
- OncLive Regulatory Report (October 7, 2026)
- Cecchini M et al., Ann Oncol 2025;36(suppl 2):S479-S480
- ClinicalTrials.gov: Study M21-404 (NCT05029882)
- ClinicalTrials.gov: Phase 3 AndroMETa-CRC Trial (NCT07525206)
