Genmab Halts PRO1107 and the Evolving PTK7 ADC Landscape

Genmab terminated its Phase 1/2 clinical trial of PRO1107 (GEN1107), an antibody-drug conjugate (ADC) targeting protein tyrosine kinase 7 (PTK7) in patients with advanced solid tumors, on September 15, 2025, due to an unfavorable benefit-risk profile after enrolling 33 participants [1].

Background on PRO1107 and PTK7

PRO1107 joined Genmab’s portfolio through its $1.8 billion acquisition of ProfoundBio in 2024, securing multiple clinical-stage ADC candidates [2,3].

PTK7, a catalytically inactive receptor tyrosine kinase, is overexpressed in solid tumors—including ovarian cancer, non-small cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC)—while largely absent in normal tissues, making it a tumor-selective ADC target [4,5].

The Phase 1/2 trial (NCT06171789) evaluated PRO1107’s safety, tolerability, pharmacokinetics (PK), and antitumor activity in advanced solid tumors, including ovarian, endometrial, TNBC, NSCLC, gastroesophageal, and urothelial cancers. The study included dose escalation/expansion (Part A) and tumor-specific expansion (Part B), but was discontinued before full completion of Part B [1].

• Stage: Terminated (Phase 1/2)
• Payload: MMAE
• Linker: Hydrophilic LD343 linker (DAR = 8)
• Antibody: Anti-PTK7 IgG1
• Notes: Acquired via Genmab’s $1.8B ProfoundBio deal; terminated due to poor benefit–risk ratio

Cofetuzumab Pelidotin: Pfizer and AbbVie’s PTK7 ADC

Cofetuzumab Pelidotin (PF-06647020/ABBV-647) is a PTK7-targeted ADC that originated from Stemcentrx, a biotech known for its ADC platforms. Pfizer partnered with Stemcentrx in 2016 to develop FIC products, including Cofetuzumab Pelidotin. Later that year, AbbVie acquired Stemcentrx for $5.8 billion, bringing Cofetuzumab Pelidotin into AbbVie’s pipeline.

The ADC was tested in Phase 1 trials for advanced solid tumors, including NSCLC and ovarian cancer. The overall ORR was ~19.6% in 56 evaluable NSCLC patients, with a higher ORR of 30% in the non-squamous, EGFR wild-type subgroup [4,6,7].

Dose-limiting toxicities (DLTs) included Grade 3 headache and fatigue at 3.7 mg/kg Q3W, and Grade 3 abdominal pain at 3.2 mg/kg Q2W. Common treatment-related adverse events (TRAEs) were nausea (44.6%), fatigue (36.6%), and neutropenia (28.6%), with only ~2.7% of patients discontinuing therapy due to TRAEs. The study ultimately led Pfizer and AbbVie to discontinue Cofetuzumab Pelidotin in 2023, mainly due to modest efficacy and portfolio reprioritization, although the 30% ORR in the EGFR wild-type subgroup suggested that PTK7 remained a potentially actionable ADC target.

• Stage: Discontinued (Phase 1)
• Payload: Auristatin F-HPA (MMAF derivative)
• Linker: Cleavable peptide linker
• Antibody: Humanized IgG1 against PTK7
• Notes: Ovarian, NSCLC trials; limited efficacy and strategic reprioritization led to discontinuation (2023)

DAY301: Emerging PTK7 ADC

Day One Biopharmaceuticals licensed MTX-13 (DAY301) from MabCare in July 2024 for $55 million upfront plus up to $1.15 billion in milestones, obtaining worldwide rights (ex-China) [9].

• IND clearance: April 2024 (FDA)
• Phase 1a trial (NCT06752681): initiated Q4 2024; enrolling NSCLC, ovarian, and other solid tumors

Preclinical studies showed broad antitumor activity in PTK7+ tumor models. The exatecan payload may offer a wider therapeutic index than auristatin-based PTK7 ADCs [5,8,10].

• Stage: Phase 1a (dose escalation, NCT06752681)
• Payload: Exatecan (DX-8951)
• Linker: T1000 conjugation with cleavable Val-Ala linker
• Antibody: Ab13 (anti-PTK7)
• Notes: Licensed global rights ex-China for $55M upfront; first-in-human trial in NSCLC, ovarian, other solid tumors

SKB518: Kelun’s PTK7 ADC Reaches Phase II

Kelun Pharmaceutical’s SKB518 has emerged as the most advanced PTK7 ADC in development.

• A first-in-human Phase 1 trial (NCT06428331) is ongoing in advanced/metastatic solid tumors, evaluating safety, tolerability, PK, and antitumor activity (estimated enrollment: 150; completion 2026) [14].
• In parallel, a Phase 2 trial in lung cancer (NCT07019675) was initiated in June 2025, enrolling 80 patients across multiple centers, making SKB518 the first PTK7 ADC to enter Phase II development [14].

Mechanism of action: SKB518 is built on Kelun’s proprietary OptiDC™ ADC platform and employs the GGFG-Dxd linker-payload, a topoisomerase I inhibitor, replacing earlier microtubule/auristatin strategies. This design is intended to improve stability, efficacy, and widen the therapeutic window in solid tumors.

• Stage: Phase 1 (solid tumors); Phase 2 (lung cancer)
• Payload: GGFG–Dxd (exatecan derivative)
• Linker: Cleavable tetrapeptide (GGFG)
• Antibody: Humanized anti-PTK7
• Notes: Most advanced PTK7 ADC; OptiDC platform; global first-in-human study ongoing

LY4175408: Eli Lilly’s Entry into PTK7 ADCs

Eli Lilly initiated a first-in-human Phase 1a/1b trial of LY4175408 (NCT07046923) in July 2025, evaluating safety, tolerability, PK, and preliminary efficacy in participants with advanced solid tumors [15].

• Indications: NSCLC, small-cell lung cancer, endometrial carcinoma, triple-negative breast cancer (TNBC), and metastatic cancers.
• Trial design: Up to 240 patients; global multi-center trial (EU CTIS: 2025-521916-20-00).
• Estimated completion: Primary completion July 2030.
• Mechanism: A PTK7-targeted ADC comprising a fully human Fc-silenced antibody linked via a cleavable linker to a topoisomerase I inhibitor payload (exatecan). Preclinical models demonstrate activity across a range of PTK7-expressing tumors, including low and moderate expressers.

This trial underscores big pharma’s renewed interest in PTK7 as a clinically actionable ADC target, following earlier setbacks from Pfizer/AbbVie and Genmab.

• Stage: Phase 1a/1b (NCT06670393)
• Payload: Exatecan
• Linker: Proprietary cleavable linker (Lilly platform)
• Antibody: Humanized IgG against PTK7
• Notes: Global multi-center FIH trial (2025–2030); exploring efficacy in low PTK7–expressing tumors

HWK-007: Whitehawk Therapeutics’ Preclinical PTK7 ADC

Whitehawk Therapeutics, formerly Aadi Bioscience, is developing HWK-007, a PTK7-targeted ADC in preclinical stage, acquired from WuXi Biologics and Hangzhou DAC in December 2024 [12].

• Stage: Preclinical
• Payload: Exatecan-like
• Linker: Stable cleavable linker (DAC platform)
• Antibody: Anti-PTK7
• Notes: Licensed from WuXi and Hangzhou DAC; plans to initiate trials in NSCLC and ovarian cancer

Emerging PTK7 ADCs

The PTK7 ADC field is expanding with new candidates:

IDE034 – IDEAYA Biosciences / Biocytogen

• Stage: Preclinical
• Payload: Exatecan-like (topoisomerase I inhibitor)
• Linker: Proprietary cleavable linker
• Antibody: Bispecific PTK7/B7-H3
• Notes: Double-targeted ADC design; nominated in late 2024 for solid tumors; potential across multiple solid tumor indications [11].

Biparatopic PTK7 ADC – Zymeworks

• Stage: Preclinical
• Payload: Exatecan-like (topoisomerase I inhibitor)
• Linker: Stable cleavable linker
• Antibody: Biparatopic anti-PTK7 format
• Notes: Demonstrated preclinical activity in breast and lung cancer models; data presented at AACR 2025 [13].

Competitive Landscape of PTK7-Targeted ADCs

Conclusion

The PTK7 ADC landscape has faced setbacks, with auristatin-based ADCs (PRO1107, Cofetuzumab Pelidotin) terminated due to benefit-risk or strategic issues.

However, Kelun’s SKB518 is now the most advanced PTK7 ADC globally, entering Phase II in lung cancer. Alongside DAY301, LY4175408, and preclinical programs (IDE034, HWK-007, Zymeworks’ biparatopic ADC), next-generation PTK7 therapies are advancing with topoisomerase I payloads, bispecific designs, and improved tolerability.

References

1. ClinicalTrials.gov. PRO1107 in Patients With Advanced Solid Tumors. NCT06171789. https://clinicaltrials.gov/study/NCT06171789
2. Genmab Completes Acquisition of ProfoundBio. https://ir.genmab.com/news-releases/news-release-details/genmab-completes-acquisition-profoundbio
3. Genmab Broadens Oncology Portfolio with ProfoundBio Acquisition. https://ir.genmab.com/news-releases/news-release-details/genmab-broaden-and-strengthen-oncology-portfolio-acquisition
4. Maitland, M. L.; et al. First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody–Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors. Clin. Cancer Res. 2021, 27, 4511–4520. https://aacrjournals.org/clincancerres/article/27/16/4511/671592/First-in-Human-Study-of-PF-06647020-Cofetuzumab
5. Kong, C.; et al. MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors. Mol. Cancer Ther. 2023, 22, 1128–1143.
6. Day One goes where Pfizer and AbbVie feared to tread. OncologyPipeline.
7. Three more Pfizer oncology projects go in latest cull. OncologyPipeline.
8. Sommerhalder, D.; et al. Phase 1 Dose Escalation and Expansion Study of the PTK7-Targeted Antibody-Drug Conjugate DAY301 in Patients with Locally Advanced or Metastatic Solid Tumors [abstract]. Cancer Res. 2025, 85(8_Suppl_2), CT196.
9. Philpott, J. Day One targets the growing ADC market with MabCare acquisition. BioSpace, June 19, 2024.
10. Day One Reports Second Quarter 2025 Financial Results and Corporate Update.
11. Biocytogen Announces IDEAYA’s Nomination of Development Candidate IDE034.
12. Whitehawk Therapeutics’ Overview and ADC Candidates.
13. Zymeworks Presents Preclinical Data on Novel ADC Programs at AACR 2025.
14. ClinicalTrials.gov. NCT06428331, NCT07019675. Studies of SKB518 in solid tumors and lung cancer.
15. ClinicalTrials.gov. NCT07046923. A Study of LY4175408 in Participants With Advanced Cancer.

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